[The function of the left heart in blockade of the left bundle of His].

A complex Doppler echocardiographic study was performed in 134 patients with complete block of the left bundle branch, its anterior branch or with concurrence of these two types of intraventricular conduction disturbance. The authors identified 5 types of paradoxical ventricular septal motion, which were related to the specific features of intraventricular asynchronism and ventricular electric systole. Type I shows the greatest decrease in left ventricular contractility, left atrial overload and phasic destruction of left ventricular systole, which reflects the processes of depolarization and repolarization propagation in the myocardium. Type IV is characterized by the lowest number of hemodynamic abnormalities. Cardiac hemodynamics is also related to the type of intraventricular block, being the least changed in isolated anterior left bundle-branch and the most changed in concurrent anterior branch and entire left bundle-branch block.


[The effect of anaprilin on the reaction of the sympathetic-adrenal system to graded physical loading in healthy subjects and patients with ischemic heart disease].

The specific features of responses of the sympathoadrenal system during its activation by graded exercise (E), including that along with anaprilin induced blockade of beta-adrenoceptors, were determined from the urinary excretion of norepinephrine, epinephrine, dopamine, and dioxyphenylalanine in 54 healthy males and 22 patients with postinfarction cardiosclerosis concurrent with Functional Class I-II angina pectoris on effort. E caused hyperreactivity of the sympathoadrenal system, as appeared as significantly greater increases in the levels of catecholamines and their precursors in the patients than in the healthy persons. A single anaprilin dose of 40 mg abolished the responsiveness to exercise and improved its tolerance. The revealed features of sympathoadrenal responsiveness to exercise with and without anaprilin suggest that the patients with coronary heart disease have sympathoadrenal dysfunction, which shows one of the possible mechanisms responsible for the cardioprotective effect of beta-adrenoblockers in this disease.


[The triglyceride content in the high-density lipoproteins of patients with ischemic heart disease].

The sera and high density lipoprotein (HDL) fraction obtained from donors and patients with coronary heart disease, Functional Class II exercise-induced angina or postinfarction cardiosclerosis were studied for levels of triglycerides (TG) and cholesterol (C) and calculated for percentage of HDL cholesterol of total serum cholesterol, C/TG and HDL C/HDL TG ratios. A TG-enriched HDL fraction was detected, which had an unusual structure. Calculation of the percentage of HDL C of serum total cholesterol levels much more revealed lower concentrations of HDL C.


[A comparative evaluation of the importance of transesophageal electrical stimulation of the left atrium and of bicycle ergometry in the diagnosis of ischemic heart disease in patients with arterial hypertension].

To make a comparative assessment of transesophageal left atrial pacing (TLAP) and bicycle ergometry (BE) in the diagnosis of coronary heart disease (CHD) in patients with arterial hypertension (AH) of different origin, the authors examined 56 patients. The patients underwent TLAP and selective coronary angiography, of them 39 patients had BE testing. No significant differences were found in their specificity (73 and 78%) and sensitivity (92 and 81%) between TLAP and BE, respectively. The maximum heart rate in CHD patients with AH was significantly higher (130 +/- 6 per min) during TLAP than that in BE (112 +/- 5 per min, p > 0.05), ischemic changes occurring at the same value of double product despite the mode of myocardial ischemia induction in these functional tests (240 +/- 10 and 236 +/- 12 arbitrary units, respectively; p < 0.05). The mean systolic blood pressure was higher in TLAP and in BE (210 +/- 10 and 185 +/- 8 mm Hg). This follows that TLAP and BE finding are comparable and no profound changes occur in TLAP, hence it can be recommended for wide application in the diagnosis of CHD in AH patients.


[The effect of verapamil on the course of stenocardia of effort, on the blood serum lipid level and on the basic indices of carbohydrate metabolism during the long-term use of the preparation].

The therapeutical efficiency of verapamil given for 3 months was studied in 36 patients with stable exercise-induced angina by multistep gradually increasing bicycle ergometry exercise test. The effects of the agent on serum lipid levels were evaluated in 30 cases. The therapeutical effect was achieved in 24 patients; verapamil caused a pronounced increase in physical working capacity just during the acute drug test in all cases and showing growing effects within a month of treatment. No increase in therapeutical effects was observed in 12 cases in whom a rise in exercise time was insignificant during the acute drug test. Verapamil produced no noticeable effect on fasting serum glucose and insulin levels after glucose tolerance test in 19 healthy individuals and 11 patients with lower carbohydrate tolerance. Thirteen patients with primary hypercholesterolemia had decreased levels of total cholesterol due to low density lipoprotein cholesterol.


[The effect of transvenous laser therapy on lipid peroxidation function in patients with ischemic heart disease].

The papers deals with changes in the levels of lipid peroxidation products in patients with stable angina of effort, which occurred with intravenous helium-neon blood irradiation. The therapy was highly effective in patients with lower functional classes and persons with normal circulation, resulting in a reduction in lipid peroxidation intensity. Predictors are recommended to determine the efficiency and expediency of laser therapy in patients with coronary heart disease.


[Changes in hypophyseal-thyroid system function and in the level of atrial natriuretic factor and cyclic nucleotides in the blood of patients with ischemic heart disease exposed to ultrasonic irradiation of the precordial area].

Radiation of the precordial region with ultrasound at 880 kHz, 0.4 W/cm2 for 12 minutes was examined for its impact on blood levels of thyrotropin, tri-iodothyronine, thyroxine, atrial natriuretic factor, cyclic nucleotides (cAMP and cHMP) in 70 patients with Functional Classes II-III exercise-induced angina. The radiation was found to lead to elevated plasma levels of atrial natriuretic factor, cHMP and inhibited plasma cAMP in patients with coronary heart disease as compared to the control group.


[The treatment of hypertension by adaptation to high-altitude hypoxia].

Ethnically close male populations aged 30-59 years who reside in high mountains (2800-3600 m above the sea level) and in low lands (800-900 m above the sea level) of the Tien Shan and the Pamirs were screened. The incidence of essential hypertension was found to be significantly lower (4.2%) among the highlanders than in the lowlanders (15.4%). In highlanders, hypertension is characterized by a high concurrence with high-altitude arterial hypertension and right ventricular hypertrophy. Daily urinary aldosterone excretion is substantially lower in residents of high mountains and natriuresis is higher than that in those from low-lands. Sixty-eight patients with mild hypertension took daily treatment as pressure chamber uplifting (3200 m above the sea level; pO2 112 mm Hg) for 15 days and 45 patients with moderate hypertension were treated with medium-land (1600 m; pO2 134 mm Hg) adaptation for 24 days. Pressure chamber hypoxic training and medium-land adaptation in 69% of patients with mild hypertension and 64.4% with moderate hypertension without signs of target organ lesions produced steady antihypertensive effects, a steady-state (for a 1.5-year follow-up) decrease in cardiac mechanical work, peripheral vascular resistance, arterial impedance, and an improvement of physical fitness. It was proposed to use hypoxic (pressure chamber and high-altitude) training for the treatment of early hypertensive disease and its secondary prevention.


[The radionuclide diagnosis of dilated cardiomyopathy: a new approach to assessing myocardial perfusion function by 201Tl scintigraphic data at rest and during the performance of the dipyridamole test].

A method for quantitative determination of the percentage of left ventricular myocardial 201Tl isotope uptake at rest and during dipyridamole test was first used in patients with dilated cardiomyopathy and coronary heart disease complicated by circulatory insufficiency or chronic myocarditis. This method makes it possible to judge the level of myocardial blood flow and perfusion reserve in these diseases. The most common differences were found between patients with coronary heart disease and those with chronic myocarditis. The patients with chronic myocarditis exhibited the greatest sizes of perfusion defects, highest values of 201Tl uptake at rest and a lower myocardial perfusion reserve during dipyridamole test. In response to exercise, most patients with chronic myocarditis had diminished perfusion defects, whereas those with coronary heart disease displayed increased defects. The myocardial perfusion was varied in patients with dilated cardiomyopathy. Some patients had a scintigraphic pattern close to that in patients with chronic myocarditis and others had a pattern identical to that in patients with coronary heart disease.


[The possibility of determining the functional status of the hypertrophied myocardium in multiple valvular defects of the heart].

A comprehensive angiocardiographic study with computer-aided data processing were performed in 46 patients (mean age 34.2 years) with multivalvular diseases. Thirty two patients were diagnosed as having mitral and aortic defect, 14 had mitral, aortic and tricuspid defect. Three-valve disease, unlike two-valve disease, showed a "paradoxical" improvement in some parameters, such as end-diastolic volume, end-systolic volume, myocardial mass, ventricular performance rates. An analysis of circular intramyocardial tension, coronary sinus blood oxygen extraction and saturation indicated that myocardial function was less intensive in three-valve disease, suggesting the compensatory pattern of tricuspid valve involvement. However, this "compensation" results in a further decrease in cardiac output and cannot be regarded as a genuine compensation. In multivalvular disease, the integral intramyocardial tension and its ratio to coronary sinus blood oxygen saturation may serve as the only diagnostic criterion for myocardial dysfunction and a predictor in determining the outcome of surgical intervention.


[The importance of the noninvasive scintigraphic assessment of pulmonary arterial pressure in persons who have had an acute myocardial infarct].

Twenty-two patients with a history of acute myocardial infarction underwent pulmonary perfusion scintigraphy at rest and during bicycle exercise testing. 99mTc-labelled human albumin microspheres were used. The perfusion ratio in the upper and lower pulmonary regions (U/L ratio) was calculated from scintigraphic findings. There was a close correlation between mean pulmonary blood pressure and U/L ratio (r = 0.95). It was established that the absence of microcirculatory bed reserve scintigraphically revealed in the lesser circulation in patients with prior myocardial infarction may be considered to be a negative predicator.


[A comparison of the efficacy of nitrogranulong and other prolonged-action nitrates by using paired bicycle ergometry in patients with stenocardia].

The efficacy of single doses of nitrogranulong, 5.2 mg, trinitrolong, 2 mg, nitrong 6.5 mg, and placebo was evaluated in 10 males aged 46-62 years who had Functional Classes II-III angina on effort. For this, paired bicycle ergometry was employed. In patients in whom nitrogranulong, 5.2 mg, turned out to be ineffective, the effective dose was evaluated as 10.4 mg. The effect of a drug was evaluated from an increase in exercise duration before the occurrence of a moderate anginal attack and/or 1 mm or more ST-segment depression in bicycle ergometry performed when the maximum effect of the single dose was expected than that in bicycle ergometry performed before achieving the same criteria for exercise discontinuation on the same day before the drug use (delta T threshold). The single dose of a drug was considered to be beneficial at delta T threshold > or = 120 sec (individual effects). Trinitrolong in a dose of 2 mg turned out be the most effective: there was the most mean value of delta T threshold and the individual effect was seen in 100% of the patients. According to the accepted criterion, nitrogranulong, 5.2 mg, and nitrong, 6.5 mg, were effective in 20%. Nitrogranulong, 10.4 mg, was beneficial in more 40% of patients; in all the first and the second doses of the drug were beneficial in 60%.


[The prognosis and prevention of syncopal states and sudden death in patients with a complete atrioventricular block in disorders of permanent cardiac electrostimulation].

A total of 105 patients with implantable pacemakers were examined. Whether the pacemaker disconnection test can be used to predict syncopes in failure of permanent cardiac pacing was studied. The spontaneous ventricular activity was evaluated in 62 patients with acquired complete atrioventricular block (CAVB) and in 43 patients with artificial CAVB. The patients with varying pacemaker dependence were grouped. It was ascertained that 7% of patients with artificial CAVB and 19% of those with acquired CAVB were dependent on pacemakers. In possible failure of stimulation or in reimplantation of a pacemaker on its disconnection, 93% of patients with artificial CAVB and 81% with acquired CAVB could develop their own cardiac rhythm. Lowering the frequency of pacing enabled the duration of asystole to be decreased. The usage of isadrin was demonstrated to enhance spontaneous ventricular activity.


[The results of conducting a program for the supplementary education of medical workers in the problems of preventing and treating arterial hypertension (a population study)].

A programme on supplementary health education of medical staff from city polyclinics in the prevention and treatment of arterial hypertension was launched in one of the Moscow districts for 3 years. Another district was used as a comparison subject. Representative samples of residents aged 35-64 years from the two districts were screened before and after implementation of the programme. The WHO International MONICA programme was used to evaluate the efficiency of the programme proposed by the authors. The intervention district showed an improvement of hypertensives' awareness of the disease and a double increase in the number of patients with a high compliance. In the comparison district, these parameters remained unchanged. According to the criteria developed in the MONICA programme, there was a downward tendency in the incidence of myocardial infarction and stroke and these diseases-related deaths in the intervention district, whereas this was not observed in the district under comparison.


Hyperkalemia: mechanisms, etiology, and treatment.

Hyperkalemia may follow failure of glomerular filtration or tubular secretion of potassium. Tubular secretory failure may be secondary to deficient aldosterone or tubular insensitivity to this hormone. In either case glomerular insufficiency magnifies the problem. Increased potassium intake alone is a rare cause of increased serum potassium. The well recognized sequential treatment of hyperkalemia is reviewed. Most important is the establishment of the cause of hyperkalemia as these emergency measures are being taken. A history of drug intake, establishment of the acid-base status of the patient and the presence of underlying disease must be ascertained. The management of hyperkalemia remains an intriguing challenge in the office and hospital practice of medicine.


Immobilization hypercalcemia in an adult patient with pancreatitis and sepsis: case report.

We describe an adult patient who developed persistent hypercalcemia while bedridden for more than three months with pancreatitis and sepsis. On the basis of hypercalciuria, suppressed serum intact PTH, suppressed serum 1,25-dihydroxy vitamin D3 and no clinical evidence of malignancy, the diagnosis of immobilization hypercalcemia was established His hypercalcemia improved during treatment with saline, calcitonin and/or etidronate. With active mobilization and weight-bearing exercises, serum calcium finally normalized. We discuss clinical and laboratory features as well as current modalities of treatment of this rare form of hypercalcemia in adults.


Cardiac mechanics in the stage-16 chick embryo.

A theoretical model is presented for the tubular heart of the stage-16 chick embryo (2.3 days of a 21-day incubation period). The model is a thick-walled, pseudoelastic cylindrical shell composed of three isotropic layers: the endocardium, the cardiac jelly, and the myocardium. The analysis is based on a shell theory that accounts for large deformation, material nonlinearity, residual strain, and muscle activation, with material properties inferred from available experimental data. We also measured epicardial strains from recorded motions of microspheres on the primitive right ventricles of stage-16 white Leghorn chick embryos. Relative to end diastole, peak axial and circumferential Lagrange strains occurred near end systole and had similar values. The magnitudes of these strains varied along the longitudinal axis of the heart (-0.16 +/- 0.08), being larger near the ends of the primitive right ventricle and smaller near midventricle. The in-plane shear strain was less than 0.05. Comparison of theoretical and experimental strains during the cardiac cycle shows generally good agreement. In addition, the model gives strong stress concentrations in the myocardial layer at end systole.


Running on an incline.

Seven male subjects ran at 3.0 m/s on a motorized treadmill including a force platform under the tread. The subjects ran at each of five treadmill inclinations: +0.17, +0.077, 0, -0.077, and -0.17 radians. The position of the subjects' legs were read from ciné films (100 frames/s). Results of the film and force plate analysis generally corroborated the "hanging triangle" hypothesis, which postulates that the angle between the leg and the vertical upon foot strike does not change as the treadmill is tipped up or down. A mathematical model of running, in which the leg is represented as a nonlinear spring, made satisfactory predictions of the way many parameters of running change with the treadmill angle, including the length of the leg at touchdown and liftoff and the peak leg force in the middle of a step. The peak leg force reaches a maximum at a treadmill angle near -0.12 radians, close to the downhill angle where other authors have found a minimum in the rate of oxygen consumption.


Testing of a biomechanical model of the lumbar muscle force distribution using quasi-static loading exercises.

The study of lumbar muscle force distribution in response to externally applied loads is based on the introduction of biomechanical models of the lumbar region. The evaluation of such models requires the execution of loading exercises while monitoring the EMG activity of certain lumbar muscles. This work uses muscle activity maps as the major design tool of such exercises, provided that the subject is constrained to an upright erect posture. The maps describe the predicted muscle force for a given combination of externally applied bending moments. A series of shoulder adduction exercises were designed and the EMG signals of eight lumbar muscles were measured while subjects performed the exercises. The results show good agreement between the model predictions and the EMG measurements, especially when the load and the muscle were contralateral to one another.


A parameter optimization approach for the optimal control of large-scale musculoskeletal systems.

This paper describes a computational method for solving optimal control problems involving large-scale, nonlinear, dynamical systems. Central to the approach is the idea that any optimal control problem can be converted into a standard nonlinear programming problem by parameterizing each control history using a set of nodal points, which then become the variables in the resulting parameter optimization problem. A key feature of the method is that it dispenses with the need to solve the two-point, boundary-value problem derived from the necessary conditions of optimal control theory. Gradient-based methods for solving such problems do not always converge due to computational errors introduced by the highly nonlinear characteristics of the costate variables. Instead, by converting the optimal control problem into a parameter optimization problem, any number of well-developed and proven nonlinear programming algorithms can be used to compute the near-optimal control trajectories. The utility of the parameter optimization approach for solving general optimal control problems for human movement is demonstrated by applying it to a detailed optimal control model for maximum-height human jumping. The validity of the near-optimal control solution is established by comparing it to a solution of the two-point, boundary-value problem derived on the basis of a bang-bang optimal control algorithm. Quantitative comparisons between model and experiment further show that the parameter optimization solution reproduces the major features of a maximum-height, countermovement jump (i.e., trajectories of body-segmental displacements, vertical and fore-aft ground reaction forces, displacement, velocity, and acceleration of the whole-body center of mass, pattern of lower-extremity muscular activity, jump height, and total ground contact time).


A constitutive theory for biomembranes: application to epicardial mechanics.

We present a new theoretically motivated experimental approach for identifying the functional form of a constitutive relation for any nonlinear, anisotropic pseudoelastic biological membrane. The utility of this approach is illustrated by identifying, from biaxial data, a new constitutive relation for excised ventricular epicardium. Values of the associated material parameters are calculated and compared for right and left ventricular specimens. Based on our findings, we suggest that there are no significant differences in the biomechanical behavior of epicardium excised from the right and left ventricular free walls of canine hearts.


An analytical study of cryosurgery in the lung.

The process of freezing in healthy lung tissue and in tumors in the lung during cryosurgery was modeled using one-dimensional close form techniques and finite difference techniques to determine the temperature profiles and the propagation of the freezing interface in the tissue. A thermal phenomenon was observed during freezing of lung tumors embedded in healthy tissue, (a) the freezing interface suddenly accelerates at the transition between the tumor and the healthy lung, (b) the frozen tumor temperature drops to low values once the freezing interface moves into the healthy lung, and (c) the outer boundary temperature has a point of sharp inflection corresponding to the time at which the tumor is completely frozen.


The effects of large blood vessels on temperature distributions during simulated hyperthermia.

Several three-dimensional vascular models have been developed to study the effects of adding equations for large blood vessels to the traditional bioheat transfer equation of Pennes when simulating tissue temperature distributions. These vascular models include "transiting" vessels, "supplying" arteries, and "draining" veins, for all of which the mean temperature of the blood in the vessels is calculated along their lengths. For the supplying arteries this spatially variable temperature is then used as the arterial temperature in the bioheat transfer equation. The different vascular models produce significantly different locations for both the maximum tumor and the maximum normal tissue temperatures for a given power deposition pattern. However, all of the vascular models predict essentially the same cold regions in the same locations in tumors: one set at the tumors' corners and another around the inlets of the large blood vessels to the tumor. Several different power deposition patterns have been simulated in an attempt to eliminate these cold regions; uniform power in the tumor, annular power in the tumor, preheating of the blood in the vessels while they are traversing the normal tissue, and an "optimal" power pattern which combines the best features of the above approaches. Although the calculations indicate that optimal power deposition patterns (which improve the temperature distributions) exist for all of the vascular models, none of the heating patterns studied eliminated all of the cold regions. Vasodilation in the normal tissue is also simulated to see its effects on the temperature fields.(ABSTRACT TRUNCATED AT 250 WORDS)


Estimation of organ transport function: model-free deconvolution by recursive quadratic programming optimization.

A model-free deconvolution method is proposed for evaluating the frequency distribution function of organ transit times. The deconvolution is treated as a nonlinear constrained optimization problem and it is solved by using a modified constrained variable metric approach. The only constraint implemented in the solution is that all the discrete transport function values are not allowed to become negative. The method is tested on model mathematical systems of known analytical transport functions. The tests are performed on systems that included noise in both the input and output functions. The criteria of successful deconvolution are the reconvolution error and, most importantly, the deviation of the computed transport function from the known analytical one. The proposed method is then applied, as a pilot experiment, to biological data obtained from an isolated, perfused rabbit lung preparation contained within a plethysmograph. The results indicate that this type of deconvolution produces stable estimates which faithfully follow the analytical function while negating the need to assume either any functional form for the behavior of the transport function or any educated initial guess of its values.


Numerical simulation for the propagation of nonlinear pulsatile waves in arteries.

The behavior of nonlinear pulsatile flow of incompressible blood contained in an elastic tube is examined. The theory takes into account the nonlinear convective terms of the Navier-Stokes equations. The motion of the arterial wall is characterized by a set of linearized differential equations. The region bounded by the flexible arterial wall is mapped into a fixed area in which numerical discretization takes place. The finite element method (Galerkin weighted residual approach) is used for the solution of this nonlinear system. The results obtained are pressure distribution, velocity profile, flow rate and wall displacements along the elastic tube (20 cm long).


Numerical simulation of steady flow in a two-dimensional total artificial heart model.

In this paper, a numerical simulation of steady laminar and turbulent flow in a two-dimensional model for the total artificial heart is presented. A trileaflet polyurethane valve was simulated at the outflow orifice while the inflow orifice had a trileaflet or a flap valve. The finite analytic numerical method was employed to obtain solutions to the governing equations in the Cartesian coordinates. The closure for turbulence model was achieved by employing the k-epsilon-E model. The SIMPLER algorithm was used to solve the problem in primitive variables. The numerical solutions of the simulated model show that regions of relative stasis and trapped vortices were smaller within the ventricular chamber with the flap valve at the inflow orifice than that with the trileaflet valve. The predicted Reynolds stresses distal to the inflow valve within the ventricular chamber were also found to be smaller with the flap valve than with the trileaflet valve. These results also suggest a correlation between high turbulent stresses and the presence of thrombus in the vicinity of the valves in the total artificial hearts. The computed velocity vectors and turbulent stresses were comparable with previously reported in vitro measurements in artificial heart chambers. Analysis of the numerical solutions suggests that geometries similar to the flap valve (or a tilting disk valve) results in a better flow dynamics within the total artificial heart chamber compared to a trileaflet valve.


Flow studies in canine artery bifurcations using a numerical simulation method.

Three-dimensional flows through canine femoral bifurcation models were predicted under physiological flow conditions by solving numerically the time-dependent three-dimensional Navier-stokes equations. In the calculations, two models were assumed for the blood, those of (a) a Newtonian fluid, and (b) a non-Newtonian fluid obeying the power law. The blood vessel wall was assumed to be rigid this being the only approximation to the prediction model. The numerical procedure utilized a finite volume approach on a finite element mesh to discretize the equations, and the code used (ASTEC) incorporated the SIMPLE velocity-pressure algorithm in performing the calculations. The predicted velocity profiles were in good qualitative agreement with the in vivo measurements recently obtained by Jones et al. The non-Newtonian effects on the bifurcation flow field were also investigated, and no great differences in velocity profiles were observed. This indicated that the non-Newtonian characteristics of the blood might not be an important factor in determining the general flow patterns for these bifurcations, but could have local significance. Current work involves modeling wall distensibility in an empirically valid manner. Predictions accommodating these will permit a true quantitative comparison with experiment.


Non-Newtonian flow patterns associated with an arterial stenosis.

A non-Newtonian constitutive equation for blood has been introduced in this paper. Using this equation, blood flow attributes such as velocity profiles, flowrate, pressure gradient, and wall shear stress in both straight and stenotic (constricted) tubes have been examined. Results showed that compared with Newtonian flow at the same flowrate, the non-Newtonian normally features larger pressure gradient, higher wall shear stress, and different velocity profile, especially in stenotic tube. In addition, the non-Newtonian stenotic flow appears to be more stable than Newtonian flow.


Wall shear stress estimates in coronary artery constrictions.

Wall shear stress estimates from laminar boundary layer theory were found to agree fairly well with the magnitude of shear stress levels along coronary artery constrictions obtained from solutions of the Navier Stokes equations for both steady and pulsatile flow. The relatively simple method can be used for in vivo estimates of wall shear stress in constrictions by using a vessel shape function determined from a coronary angiogram, along with a knowledge of the flow rate.


Measurement of steady-flow instability and turbulence levels in Dacron vascular grafts.

Fluid dynamic properties of Dacron vascular grafts were studied under controlled steady-flow conditions over a Reynolds number range of 800 to 4500. Knitted and woven grafts having nominal diameters of 6 mm and 10 mm were studied. Thermal anemometry was used to measure centerline velocity at the downstream end of the graft; pressure drop across the graft was also measured. Transition from laminar flow to turbulent flow was observed, and turbulence intensity and turbulent stresses (Reynolds normal stresses) were measured in the turbulent regime. Knitted grafts were found to have greater pressure drop than the woven grafts, and one sample was found to have a critical Reynolds number (Rc) of less than one-half the value of Rc for a smooth-walled tube.


On the subclavian steal syndrome in vitro studies.

An elastic model of the arterial system has been used in which a specially designed pumping unit simulated the heart action. Physiological pressures and normal geometry, size, and flow distribution together with the normal cardiac output and use of prosthetic heart valves are the features of the system. Atherosclerosis was simulated by introducing blockages of known cross-section at specific sites of predilection. It has been shown that, for some specific occlusion magnitude in the left or right subclavian, or in the brachycephalic arteries, the stagnant no blood flow condition will appear in the left vertebral, or the right vertebral, or right common carotid, or the right internal carotid arteries. For larger occlusions the blood flow in these arteries reverses its direction, i.e., the "steal syndrome" appears. It is shown that besides the known single steal syndrome there exists also a double steal syndrome, i.e., blood reverses its flow direction simultaneously in two arteries, both on the right side of the arterial system. This blood is taken from the circle of Willis, which at the same time is significantly supplemented by the increased blood flow through the other arteries leading into the circle of Willis.


In vivo measurement of leukocyte viscosity during capillary plugging.

Leukocyte plugging of capillaries in vivo was measured in rat spinotrapezius muscle. The plug durations, leukocyte and capillary dimensions, and arteriolar pressure at the plug sites were applied to the mechanical model of Needham and Hochmuth (1990) to estimate the leukocyte viscosities. The viscosity distribution of 389 cells was lognormal with a median value of 232 Poise. 3.1 percent of the cells were apparently activated and displayed viscosities greater than 3000 Poise. The median viscosity suggests that inactivated leukocytes have a minimal effect on blood flow, but that leukocyte activation may result in significant increases in microvascular flow resistance.


The bleed off perfusion term in the Weinbaum-Jiji bioheat equation.

The microvascular organization and thermal equilibration of the primary and secondary arteries and veins that comprise the bleed off circulation to the muscle fibers from the parent countercurrent supply artery and veins are analyzed. The blood perfusion heat source term in the tissue energy equation is shown to be related to this vascular organization and to undergo a fundamental change in behavior as one proceeds from the more peripheral tissue, where the perfusion term is proportional to the Ta--Tv difference in the parent supply vessels, to the deeper tissue layers where the bleed off vessels themselves form a branching countercurrent system for each muscle tissue cylinder and the venous return temperature can vary between the local tissue temperature and Ta. The consequences of this change in behavior are examined for the Weinbaum-Jiji bioheat equation and a modified expression for the effective conductivity of perfused tissue is derived for countercurrent bleed off exchange.


The variation of isometric energy rates with muscle length: a distribution-moment model analysis.

The Distribution-Moment Model of skeletal muscle, which has been enhanced recently to make possible the calculation of chemical energy release (E) and heat production (H) rates [1], is applied to isometric muscle. Under steady-state isometric conditions the model predicts a simple relation between the energy rates and the muscle length, namely (E/Emax) = (H/Hmax) = [1 + B alpha(symbol see text)]/[1 + B], where (symbol see text) is the ratio of muscle length to the "optimal" length at which maximal isometric tension is produced, and alpha (symbol see text) is a function numerically equal to the ratio of the tetanic isometric force to its maximum value. The single dimensionless constant in this relation, B, can be calculated from model parameters characterizing muscle dynamics at the optimum length, and has a value near unity for frog sartorius at 0 degrees C. The predicted behavior is shown to agree reasonably well with experimental measurements of heat production and phosphocreatine (PCr) hydrolysis. The model relates the isometric energy rates to PCr hydrolysis in (1) cross-bridge interactions, and (2) calcium pumping into the sarcoplasmic reticulum.


Motion of a doublet of two cylinders in contact in a narrow channel flow.

The motion of two rigid circular cylinders in contact immersed in an incompressible Newtonian fluid in a channel is examined numerically in the zero Reynolds number limit, for various values of the cylinder radius/channel width ratio. Analyses of the time courses of the lateral position and the orientation of the doublet showed that, depending on the initial condition and the doublet/channel size ratio, the doublet exhibit one of the three types of motion: a continuous rotation in the same direction during a period, and a rotation changing its direction at every half period with a large or a small variation of the orientation.


A model for estimating corneal stiffness using an indenter.

A finite element model that simulates indentation of the cornea was generated to examine the feasibility of using indentation data to determine mechanical properties. A layered model which included geometric nonlinearities was necessary to characterize the indentation process. Results indicate that a secant modulus could be determined by measuring indenter force and contact area.


Effect of electrical stimulation superimposed with isokinetic contractions.

Previous studies have considered the effects of the superimposition of electrical stimulation (ES) upon maximal voluntary contraction (MVC) under isometric conditions. This investigation considered these effects using isokinetic muscle action. Eleven males, non athletes, volunteered for the experiment. Isokinetic torque for extension of the right knee was measured by means of a Cybex 340 using two speeds of movement, 12 degrees/s and 30 degrees/s. Torque was measured at 5 degrees increments (from 100 degrees flexion to full extension) under conditions of MVC alone and MVC+ES. Stimulation was provided by means of a bi-phasic, symmetrical, square wave with a pulse width of 600 mu. Frequency of stimulation was either 30 Hz or 80 Hz. It was found that the pattern of torque production was unaffected by the application of ES. Peak torque values at both speeds were significantly lower when ES was applied at both frequencies compared to MVC alone. This inhibitory effect was found to extend throughout the middle range of movement. This tended to be more pronounced with the 80 Hz frequency. In general these findings were in agreement with those reported previously for isometric conditions. Possible explanations for these results include the inability of ES to recruit more motor units than MVC alone; the limitations of the subjects to tolerate a current of a sufficiently high intensity to elicit a stronger contraction, possibly due to lack of familiarization with these forms of muscle action; and the characteristics, especially pulse width, of the stimulating current.


Neuromuscular responses in male and female athletes to two successive strength training sessions in one day.

Acute neuromuscular responses to two successive strength training sessions performed in the same day were investigated in nine male (MSA) and ten female (FSA) strength athletes. The loads for the leg extensor muscles varied between 70 and 80% of one repetition maximum (IRM) during the morning session (I) (from 10.00 to 11.00 hours) and between 70 and 100% of IRM during the afternoon session (II) (from 16.00 to 17.00 hours). Significant decreases occurred in maximal isometric strength both in MSA from 3855 +/- 791 to 3744 +/- 882 N (p < 0.05) and in FSA from 2493 +/- 553 to 2371 +/- 523 N (p < 0.05) during session I, while only slight (ns) changes took place in the maximal neural activation (IEMG) of the exercised muscles. During session II a great decrease of 8.5 +/- 6.3% (p < 0.01) took place in maximal strength (from 3911 +/- 786 to 3556 +/- 590 N) accompanied by a shift (worsening) in the average force-time curve in MSA, while only a slight change of 2.7 +/- 6.5% (ns) occurred in maximal strength (from 2462 +/- 529 to 2398 +/- 453 N) in FSA. The individual changes in the maximum averaged IEMG of the exercised muscle during session II were correlated (p < 0.05) to the individual changes in maximal strength. The present results suggest that high but submaximal loading of the neuromuscular system may result in an acute decrease in maximal strength of the exercised muscles taking place rather similarly both in males and females.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of treadmill running on the isometric fatigue of the handgrip muscles.

Twelve male subjects, ages 18-32, performed low, moderate, and high intensity systemic treadmill exercise to examine its effect on isometric strength and fatigue of the handgrip muscles. Baseline handgrip values were recorded, as well as maximal oxygen uptake and ventilatory threshold (VT), to determine the intensity for each of the three exercise conditions. Task A involved a 10-min treadmill run at 20% below VT, task B was given at VT, and task C was 20% above VT. Immediately following the endurance treadmill run the subjects were given a 2-min isometric contraction at maximum intensity. Heart rate and blood pressure were also measured. No significant differences were found between control measures and the strength and endurance variables. Rates of fatigue were similar for all conditions, and heart rate and blood pressure remained elevated during the handgrip fatigue task. It is concluded that isometric strength and endurance of non-involved muscles are not affected by prior endurance exercise.


Fitness characteristics of competitors in a six day sailboard marathon.

The purpose of this study was to profile the fitness characteristics of competitors in a 6 day sailboard marathon and assess the aerobic demands encountered. Twenty one male sailboarders were assessed for body composition, horizontal shoulder adduction and abduction strength as well as grip strength. Body composition was assessed by skinfold measurement and strength measured by dynamometer. A subgroup of 5 subjects were assessed for VO2 max by indirect calorimetry using a treadmill protocol. Functional capacity was determined as the quotient of VO2 max and the VO2 at rest and the aerobic conditioning threshold estimated. The corresponding threshold heart rate was determined. During each days racing, heart rate was continuously monitored from 2 different members of the subgroup. In the total group body fat was 19.1 +/- 5.1%, grip strength was 502.3 +/- 61.8 N and horizontal shoulder adduction and abduction strength was 449.3 +/- 121.6 N and 437 +/- 94.2 N respectively. In the subgroup, VO2 max was 49.6 +/- 3.7 ml/kg/min, functional capacity was 8.8 +/- 0.9 METS and threshold heart rate occurred between 155 +/- 5.2 and 161 +/- 4.6 beats/min. Heart rate response during sailing was typically in the 120-150 beats/min range. The results indicated that sailboarding does not promote high levels of aerobic fitness.


Physiological response to water aerobics.

Heart rate (HR) and oxygen uptake (VO2) measured during water aerobics (WA) were compared to maximal values obtained during an incremental treadmill test to assess the energy demand and potential cardiorespiratory (CR) training effects of WA. Sixteen college-age females served as subjects (mean +/- SD = 20.4 +/- 1.6 years). WA elicited a mean HR of 162 b.min-1 and a mean VO2 of 18.4 ml.kg-1.min-1 which represented 74% of HR reserve, 82% of maximal HR, and 48% of VO2 max. Average caloric expenditure was 5.7 kcal.min-1. HR values for WA were consistent with guidelines established by the American College of Sports Medicine for developing and maintaining CR fitness in healthy adults. However, the VO2 fell just below the recommended minimum threshold level. It was concluded that WA may provide an attractive alternative to traditional modes of exercise for improving CR fitness, however, HR measures may overestimate the metabolic intensity of the exercise.


Evaluation of anaerobic performance capacity by the isokinetic Ariel computerized exercise system-reliability and validity.

The present study examines the reproducibility and validity of computerized muscle strength and endurance evaluation protocols using the Ariel Computerized Exercise System (ACE). Since the ACE has only recently become commercially available, there are no published normative data for various exercises, nor are the measurements' accuracy and validity for the various exercise protocols documented. Twenty males (17 to 30 years old) performed a set of isokinetic maximal leg and arm exercises on the ACE Multi Function Unit twice on 2 separate days. Test-retest correlation coefficient ranged from 0.44 (bench press) to 0.91 (bench pull and leg extension flexion). Thirty additional male subjects (16 to 31 years old) performed, on 2 separate days, the Wingate Anaerobic Test (WAnT) (leg), and various force and endurance leg exercises (squat) on the ACE. Correlation coefficients of the various performance indices between the 2 test systems ranged from -0.02 to 0.23. The results obtained on the ACE indicate moderate to high reproducibility and low concurrent validity with WAnT.


A comparison of the perceived and the ECG measured heart rate during cycle ergometer, treadmill and stairmill exercise before and after perceived heart rate training.

The ability to perceive exercise heart rate before and after training was tested in six young male university students, perceptions of heart rate being compared with ECG monitored heart rates during cycle ergometry, treadmill running and stairmill climbing. Between initial and final tests, subjects undertook 13 weeks of running training (2 h/day, 3-4 days/week), and during this period they compared their perceptions of heart rate with values observed on watch-type wrist-mounted pulse monitors. Individual initial perceptions showed only a moderate correlation with ECG values. This correspondence was improved as perceptions were compared with measured heart rates over the course of training, significantly so for the mode of exercise most similar to that adopted in the training sessions (treadmill running at a heart rate of 140 beats/min). The final accuracy of perceptions at a heart rate of 140 beats/min (error 8-9 beats/min during treadmill running) compared favourably with the accuracy of either pulse counting or the traditional rating of perceived exertion as commonly observed in the exercising public. This suggests that there may be an application for perceived heart rates in regulating the intensity of prescribed exercise.


A height-adjusted step test for predicting maximal oxygen consumption in males.

A suitable testing device that is generally favored for estimating maximal oxygen consumption (VO2max) under field conditions or in environments where testing equipment is limited is the step test. Recently a mathematical model was reported to standardize the height of stepping for individuals of various heights. The purpose of this study was to validate this model in males. Thirty-three men aged 18 to 47 (x = 28) performed each of three rate-specific step tests and a Bruce treadmill test. Direct measurements of VO2max obtained from the treadmill test were correlated with a 15 second recovery heart rates after three different step tests were performed at stepping frequencies of 22, 26 and 30 ascents/minute. The correlation coefficients for prediction of VO2max from the recovery heart rate and directly measured oxygen consumption were 0.77 at 22 and 0.81 at 26 and 30 ascents/minute. Each relationship was statistically significant at the p < 0.01 level. It can be concluded that the single-stage height adjusted step test provides an effective predictor of VO2max in males and can be used when more complex methods of clinical testing are unavailable or not feasible.


Physiologic comparison and validation of Stairobic stepping with bench stepping.

To compare the oxygen cost of submaximal exercise on the Stairobic stepping (SS) machine with bench stepping (BS), 12 healthy men and women (mean age 23 years) underwent six different five minute exercise bouts that were randomly assigned. Tests were conducted using standard open circuit calorimetry. SS at 40 and 60 st/min was equal to BS at 20 st/min and SS at 80 st/min was equal to BS at 30 st/min for VE and RER. VO2 was equal at 20 st/min (BS) and 60 st/min (SS), and 30 st/min (BS) and 80 st/min (SS). Stairobic MET (SM) displayed values over-estimated actual MET (AM) values at the two lowest SS rates and under-estimated the AM value at the highest SS rate. Forty-eight observations of the MET response of SS were conducted and analyzed (BMDP2R) in a forward stepping solution. The multiple regression equation calculated for AM was: AM = -0.567 + -0.012 (WT) + 0.063 (rate) + 0.612 (SM) with an adjusted R2 of 0.82 and a SEE of 0.90. The physiologic cost of BS was approximately equal to SS at two to three times the BS rate of stepping.


Cardiovascular responses to Valsalva maneuver in physically trained and untrained normal subjects.

To elucidate whether the Valsalva maneuver (VM) can distinguish different degrees of normal ventricular function and parasympathetic tone, we studied 10 physically untrained and 18 trained normal individuals who regularly performed isotonic exercises. Both groups were submitted to an exercise stress test. An electrocardiogram and an M-mode echocardiogram were recorded before and during VM. The arterial pressure, heart rate and ventricular function responses to the maneuver were evaluated. The end diastolic volume, ejection fraction, circumferential fiber shortening and left ventricular posterior wall thickness were greater at rest in the trained group than in the untrained one. In both groups, during the straining phase of the VM the volumes and end systolic stress decreased and the systolic function indexes increased, but the changes were more pronounced in the trained subjects. In spite of these differences, the arterial pressure and heart rate responses were similar in both groups. It can thus be concluded that only changes in ventricular function distinguish physically trained vs untrained subjects during VM.


The effects of a six-week, low-intensity Nautilus circuit training program on resting blood pressure in females.

Twenty-six healthy, untrained females were studied to determine the effects of a low-intensity Nautilus circuit training program on resting systolic and diastolic blood pressure. Thirteen subjects who were in good health with no personal history or family history of cardiovascular disease participated in a six-week training program on the Nautilus circuit (14 exercises) and trained at 30% of maximum. Measurements in blood pressure were made before, during (three times per week) and after the study. Another group of 13 females served as controls. An attempt was made to determine if strength increase (due to circuit training) would have an affect on reducing resting systolic and diastolic blood pressure. The following changes occurred in the treatment group: (1) resting systolic blood pressure dropped significantly (from 113 to 99 mmHg) after training and (2) diastolic blood pressure dropped significantly from (70.9 to 62.0 mmHg) after training. However, there were no differences in these decreases between the exercise and control groups. The investigators concluded that low-intensity, resistive training should not increase blood pressure in white, healthy females, ages 18 to 28 years.


Skinfolds and body composition of sports participants.

Body composition of 1815 North-Italian young sports participants in relation to sex, age, sport and level of performance was investigated. About thickness and anatomical distribution of subcutaneous fat females showed skinfolds thicker than males. Significant differences were observed in skinfold thicknesses means of different sport-groups. Subscapular and forearm skinfolds were the best discriminant variables for males and females respectively. Body density was estimated according to Katch and McArdle (1973) and Durnin and Womersley (1974) equations. Males showed higher body density and lower fat percentage values than females. The lowest value of body density and the highest fat percentage were in male martial art competitors and in females practising skating and athletics. The highest values of body density and the lowest of fat percentage were in males practising athletics and rowing and in female martial art competitors. Highest and lowest values of fat-free mass were in games players and in soccer players and gymnasts respectively. "High aptitude" subjects showed higher fat-free mass values than "middle aptitude" group, besides a tendency towards higher body density values and lower fat percentage than "middle aptitude" group. With aging body density decreased whereas fat percentage and fat-free mass increased.


Erythrocyte metabolism in exercise. A comparative study in anaemized rats.

The influence of young red cells induced by anaemization on physical performance had been studied in rats. The anemic rats with immature red cells, higher levels of ATP, glutamate-oxalacetate transaminase (GOT) and lactate dehydrogenase (LDH) showed an elevated lactate and ammonia concentration at the first week of training. The blood analysis also showed that the rise in 2,3-DPG concentration can be related with the increase of glycolytic activity during exercise in both groups, anemic and non anemics rats.


Vehicle injuries to joggers. Case report and review.

A medico-legal case is presented where a jogger was struck by a car while crossing an intersection and later sought major damages in a civil court. This incident is reviewed in the context of overall information on injury to joggers by vehicles, and the possibility (raised by the defendant's counsel) that the euphoria generated by prolonged exercise may have created a sense of "invincibility" that predisposed the jogger to reckless actions. The defendants argued that the young man concerned was taking an amount of exercise that could have led to a jogging addiction and alteration of consciousness in a susceptible individual, and a history of alcohol, drug and video addiction was advanced as evidence that he may indeed have been a susceptible person. During the actual incident, the jogger recognised that the driver of the vehicle had not seen him, but nevertheless he proceeded to enter a crosswalk that had already been 75% traversed by the car, leaving himself only 0.6 metres of space, a half of the lane width normally required by a runner. A calculation of the relative velocities of the car and the jogger suggests that the latter must have veered 1-2 metres onto the main highway in order to pass in front of the care and be hit from the side. The behaviour of the jogger was plainly reckless, but more information is needed on the relative incidence of traffic injuries in joggers and walkers, on the prevalence of jogging addiction, and on diagnostic criteria for this condition before the accident could be categorically attributed to a jogging-related euphoria.


Sixty-three years of competitive sport activity. Case study.

A very rare case of a 79-year-old long-distance runner with competitive sport experience of more than sixty-three years is being evaluated. His health status is excellent and no indication of chronic disease is evident. Data from his evaluation have shown that, morphologically and functionally, he is closer to elite runners almost 50 years younger, than other master runners of about the same age. His body fatness, VO2max, his best reaction time and his highest recent speed of movement are: 10%, 40.6 ml/kg/min-1, 196 ms, and 15.73 km/h-1, respectively. Although his muscular strength and joint flexibility are satisfactory for his age, they are much lower in comparison to elite runners. The conclusion drawn is that his almost lifelong competitive athletic activity is at the root of his superb morphological and neuromotor responsiveness, his excellent cardiovascular and respiratory systems and his ideal biochemical profile.


Biocompatibility and ingrowth of Trevira prostheses following replacement of the cruciate ligaments.

Five of 97 cruciate ligament prostheses (5.15 per cent) implanted for an average of 3 years (8-53 months) in 70 patients with acute chronic cruciate ligament instability were removed due to failure after a mean of 9 (3-15) months. Investigation of the explanted polyethylene terephthalate (PET)-grafts by scanning electron and light microscopy showed not bony but fibrous tissue ingrowth in all parts of the prostheses. The extent of local host response in the interface region differed with the intensity of mechanical strain at the three parts of the prostheses (intra-articular, bone tunnel, cortical). Inflammatory cells and foreign body giant cells were abundant close to the rupture sites at the intra-articular entries of the bone tunnels and scarce at the intra-articular part of the prostheses and at the cortical anchoring. Evaluation of the reasons for early prostheses failure indicates that (1) non-ideal placement of bone tunnels and (2) inadequate strain were responsible for reoccurring instability and rupture after prosthetic cruciate ligament replacement.


Selective laser-induced inactivation of proteins (SLIP) by labelling with chromophores.

Coupling a fluorochrome (e.g. fluorescein-isothiocyanate, FITC) to a molecule can enhance specific laser light absorption, thus leading to alteration or even destruction of the molecule itself. Therefore antibodies were labelled with FITC (absorption maximum 480 nm) and irradiated with laser light (488 nm) under various conditions. Inactivation of antibodies could only be achieved at the absorption maximum of FITC (as measured by direct and indirect immunofluorescence). Positive linear correlation exists between the amount of destruction and both exposure time and energy. Similar destructive effects were obtained when FITC-labelled peroxidase was irradiated. In these cases, enzyme activities measured by absorption photometry also showed a positive correlation to the total amount of energy transferred. Non-labelled proteins were not affected by irradiation. So we conclude that labelling of proteins with fluorochromes provides a highly specific means of selection of target molecules to be destroyed or inactivated. The method is based upon the laws of linear optics and is different from photodynamic or photochemical actions. The destructions observed are most likely caused by thermally induced changes of the molecules' tertiary structure.


Opportunities for the cellular approach in biomedical engineering.

This review is a commentary on recent, altered perspectives about biomedical engineering and its role in medicine. It is argued that, rather than being a peripheral specialty, medical engineering and engineering principles in general have a direct application to biochemical medicine and cell biology. A brief description is given of the cell as a compartmentalised reactor system, and the ways in which it is possible to replace lost or aberrant cell function. Specific topics are then covered to illustrate the general thesis. These are: polymers for cell mimicry, cell-surface interactions, biomolecule transport, cell transport phenomena, cell signalling, harnessing of cells for therapy and microbial interactions. These disparate subject areas have a common thread of interest for the biomedical engineer, and are presented here in a way which highlights key points of relevance for engineering. Though necessarily brief, the various descriptions in this review provide a film indication that a rigorous approach to the assessment, modelling and use of cells along sound engineering lines is vital for the future. It is concluded that, without this approach, our understanding of cell biology will remain semiquantitative and semiempirical.


Cellular interactions with NIR EM energy.

The electrical and electrochemical nature of cellular components, structure and function makes it important for the possible influences by externally applied electromagnetic fields to be studied thoroughly. This is an important aspect of cellular engineering. Thermal and non-thermal influences of EM, electric and magnetic fields on biological tissues are under investigation by several groups, to improve both diagnostic and therapeutic techniques. Within the EM spectrum there is an interesting band in the infra-red, from about 700 nm to 1000 nm, where absorption by enzymes within the intracellular respiratory chain can take place. This absorption phenomenon is now used as the basis for quantitative analysis of enzyme dynamics, both in vitro and in vivo, but implications for both therapeutic and potentially damaging influences on cellular behaviour and viability also need to be considered.


Modified cell proliferation due to electrical currents.

In view of the evidence that electrical currents may enhance healing of chronic wounds and retard tumour growth it is suggested that these currents normalise cell proliferation. Additional support to this contention is given by two reports: one on healing of pressure sores in man and one on tumour growth retardation in mice. The effect of an ionic environment on the cell cycle is analysed. Finally a hypothesis attempting to explain the normalising effect of electrical currents on cell proliferation is proposed. It is known that non-dividing cells, e.g. mature neurons, have high transmembrane potential (TMP) whereas fast-dividing cells, e.g. cancerous cells, have low TMP. When a cell is exposed to an electrical field, one side of the cell becomes hyperpolarised while the opposite side is depolarised. Assuming a nonlinear relationship between TMP and the transmembrane ionic currents, it can be shown that in non-dividing cells their high TMP is lowered; whereas in cells with a high division rate, their low TMP is raised due to cell exposure to the external electrical field. These alterations in transmembrane potential could contribute to the normalisation of abnormal cell proliferation.


Making real neural nets: design criteria.

Neural nets may be assembled with living nerve cells in vitro to test theories about neural processing and the ways in which patterns develop in the nervous system, and to test ideas about plasticity and learning in processing systems. This may benefit the design of computer systems and prosthetic devices. Extracting information from such nets can be achieved by means of intracellular and extracellular electrodes and fluorescent dyes. Patterning of cells may be achieved using microfabrication techniques, and extracellular electrodes can be combined within the patterned substrate.


Dendritic processing: using microstructures to solve a hitherto intractable neurobiological problem.

In vivo, intracellular recordings of mammalian brain stem motoneurones, followed by peroxidase staining and tridimensional reconstruction, suggest that the shape of the dendritic tree plays an important role in the processing of neural information. To test this hypothesis attempts were made to guide, in culture, the growth of neuritic branches of neurones dissociated from the hypoglossal nucleus of rat brain stem. This was performed using topographical and adhesive microstructures which were designed to control the shape of the neuritic tree. Guidance of the neuritic processes can be observed with small grooves engraved on quartz and plastic substrates, and simple shapes with few processes and bifurcations on each neurite could be obtained using adhesive microstructures. These procedures, which allow the shape of a neurone to be controlled, are very promising in the study, by means of classical electrophysiological methods as well as optical recordings, of the involvement of dendritic architecture in the processing of neural information.


Migration of the true pacemaker within the sinoatrial cell aggregate in man.

The functional anatomy of the sinoatrial node (SAN) in man is first reviewed, together with its possible anatomical substructure. The true group pacemaker (PM) shift under autonomic drive is then related to a continuous competition between the intrinsic auto-firing period hierarchy and the autonomic topological susceptibility hierarchy. Accordingly, the PM 'skip' to both lower and higher periods following an abrupt and consistent acetylcholine (ACh) release at the SAN periphery, and the PM 'slip' towards a relocation of the next period, as a possible response to a slower and smaller ACh release, are considered. The PM 'skip' and 'slip' as boundaries of the true PM excursion within the SAN during the respiratory cycle, and their statistical properties, are then examined. Under current heart rate control menus in normals, the PM skip appears to follow central influence, whereas the conservative or slipping PMs suggest peripheral control. Finally, interpretation of the PM skip as a salutary sign of functional reserve is proposed, and a method of alleviating the PM skip which confounds electrophysiological testing of the SAN function in patients is devised.


Tissue engineering in the USA.

Tissue engineering is the application of the principles and methods of engineering and the life sciences towards the development of biological substitutes to restore, maintain or improve functions. It is an area which is emerging in importance worldwide. In the USA it has been actively fostered by the National Science Foundation, both through research grants and the sponsorship of a series of workshops starting in 1988. This brief review of activities in the USA focuses on cell culture technology as a foundation for tissue engineering and then discusses examples of applications. These include artificial skin and the use of encapsulated cells in the development of bioartificial organs. Also discussed is the reconstitution of a blood vessel in culture, both for use in basic research and for implantation as an artificial blood vessel in bypass surgery. In conclusion, other potential applications are mentioned as well as generic areas of technology for future development.


Cardiac stimulator for the study of refractory period control using current pulses of programmable duration and shape.

A programmable current stimulator has been developed that allows unipolar current pulses of complex shape, long duration and high current to be generated. The stimulator conforms to the safety requirements for devices connected directly to the heart. It incorporates additional safety features to prevent unintended current being delivered, even under fault conditions. The stimulator has been used to investigate the effects of long duration current pulses on the refractory period of cardiac tissue. The flexibility of the device suggests that it may well have uses in other fields of electrophysiology.


Heart rate variability as an index of autonomic imbalance in patients with recent myocardial infarction.

Autonomic nervous activities are estimated in three groups of patients: Group A consists of patients who had experienced myocardial infarction (MI) within 2-6 weeks before the tests; Group B consists of patients who had MI more than one year previously; Group C consists of matched controls, free of cardiac disease. Autonomic activity is estimated using postural effects on heart rate variability (HRV): a sympathetic activity index is defined as HRV power within a low frequency band (0.04-0.12 Hz) in the tilt position and a parasympathetic activity index is defined as HRV power in a high frequency band (0.18-0.28 Hz) in the supine position. Results show that, relative to controls, Group A patients have reduced parasympathetic activity index (5 + 3 against 13 + 8, normalised units; p < 0.05) and an increased ratio of sympathetic to parasympathetic activity (17 + 17 against 4 + 2; p < 0.05). Group B is not significantly different from Group A or C. The period of 2-6 weeks post-MI thus appears to be characterised by depressed parasympathetic nervous activity which can be measured using HRV analysis.


Active response of a one-dimensional cardiac model with gap junctions to extracellular stimulation.

To study the response of cardiac tissue to electrical stimulation, a one-dimensional model of cardiac tissue has been developed using linear core-conductor theory and the DiFrancesco-Noble model of Purkinje tissue. The cable lies in a restricted extracellular medium and includes a representation of the junctional resistances known to interconnect cardiac cells. Two electrode geometries are considered: (a) a semi-infinite cable with a monopolar electrode at the end of the cable and (b) a terminated cable with one electrode at each end of the cable. In a series of simulations, stimuli of varying magnitude and polarity are applied at three different times during the plateau of the action potential. The results at the stimulus site show that the action potential duration may either decrease or increase in response to the stimulus, depending on the polarity and application time of the stimulus. The spatial behaviour of the cable in response to the stimulus indicates that sites greater than 200 cells from the stimulating electrode are not affected by the stimulus.


Use of surface potential spectral characteristics for solving the inverse problem in electroneurography.

The changes in the power spectra of single-fibre extracellular action potentials (SFEAPs) generated in an infinite anisotropic frequency-dependent volume conductor, which occurred as a result of alterations in the propagation velocity v and duration T(in) of the intracellular action potential (IAP) were analytically determined. Effects of the temporal and spatial dispersions of almost synchronously activated fibres on the power spectrum of compound extracellular potentials (CEPs) were analysed for different shapes and sizes of the activated fibres' territory. It was found that, as a result of desynchronisation in the fibres' activation, dips existed in the CEP power spectra and that the frequencies of the dips depended on the degree of desynchronisation but did not depend on the velocity. It was shown that the hypothetical power spectrum of compound IAP was sensitive to the variations in the desynchronisation in the fibres' activation and in the risetime and duration of IAP even at a great fibre electrode distance typical for surface recordings.


Improved procedure of complex demodulation and an application to frequency analysis of sleep spindles in EEG.

Complex demodulation is a local version of harmonic analysis that enables the amplitude and phase of particular frequency components of a time series to be described as functions of time. The paper presents a computational procedure involving complex demodulation with interpolation of data in the frequency domain. A computational procedure comprising repeated use of complex demodulation is also presented. This is used to estimate the optimum choice of the demodulating frequency which considerably influences the measurement of the instantaneous amplitude and phase of the underlying process. The usefulness of this procedure is verified by computer simulation. An example of applying this procedure to the estimation of the centre and the instantaneous frequencies of sleep spindles in the EEG (electroencephalogram) is presented. By using the procedure developed here, several partially overlapping sleep spindles are detected and correctly separated. The paper also presents an approach to separating and analysing transient time series (such as overlapping sleep spindles) by using an accurate frequency processing technique.


Finite-element analysis of arterial anastomoses with vein, Dacron and PTFE grafts.

A finite-element simulation of an end-to-end artery/graft anastomosis has been presented in this study to evaluate the distribution of compliance and stresses in the vicinity of the anastomosis due to any mismatch in compliance characteristics. The arterial wall was assumed to be made of linear isotropic elastic material in this simplified model and a static analysis was performed with a mean arterial pressure loading of the artery-graft model. Anastomoses to vein grafts and both Dacron and polytetrafluoroethylene (PTFE) grafts were studied. The results suggested the presence of a hypercompliant zone on the arterial side and a region of high tensile stresses in the wall on the graft side of the anastomosis. The presence of a hypercompliant zone has been reported from previous in vivo studies. The hypercompliance was larger with Dacron and PTFE grafts compared with that with the vein graft. However, larger tensile stresses were present in the wall of the vein graft compared with the synthetic grafts. The analysis further showed that increasing the diameter of the graft compared with the host artery to increase flow through the implant will result in a significant increase in the hypercompliance on the arterial side. Such simulation studies may prove valuable in studying the effects of compliance mismatch and suggest ways to improve the design of small diameter vascular grafts.


Interface load analysis for computer-aided design of below-knee prosthetic sockets.

A finite-element analysis is made for the compression of soft tissues of the residual lower limb contained in a prosthetic socket. The analysis is relevant to static loading during stance in a patellar-tendon-bearing, below-knee design of socket. Values of Young's modulus are obtained experimentally for use in the model. One of the main objectives is to study the sensitivity of the loading to these values and also to other assumed conditions. Using direct pressure at the limb/socket interface and vertical stiffness as indicators, changes in material properties, socket alignment and socket rectification are investigated; assumptions about the frictional characteristic at the interface are seen to be critical in determination of load distribution. This type of analysis may provide the next stage of refinement for computer-aided socket design systems.


Spatial localisation of NMR signals and electrical scanning of sensitive regions by the magnetic focusing method.

The spatial localisation of NMR signals by the magnetic focusing method is examined and a method for electrical scanning of a spatially localised region is proposed. The small amount of signal from points of the star taper in static field focusing can almost be neglected, and the spatial localisation of the signal corresponds to the shape of a prolate spheroid in the centre region of the star-shaped focusing field. Electrical scanning of the focused region can be achieved at any position in the magnet system by superimposing linear field gradients on the focused field in the scanning direction. These are the inherent limitations of the static magnetic field focusing method. The embodiment of the scanning movement of the focused field is also confirmed.


Electric field induced in a spherical volume conductor from arbitrary coils: application to magnetic stimulation and MEG.

A mathematical method is presented that allows fast and simple computation of the electric field and current density induced inside a homogeneous spherical volume conductor by current flowing in a coil. The total electric field inside the sphere is computed entirely from a set of line integrals performed along the coil current path. Coils of any closed shape are easily accommodated by the method. The technique can be applied to magnetic brain stimulation and to magnetoencephalography. For magnetic brain stimulation, the total electric field anywhere inside the head can be easily computed for any coil shape and placement. The reciprocity theorem may be applied so that the electric field represents the lead field of a magnetometer. The finite coil area and gradiometer loop spacing can be precisely accounted for without any surface integration by using this method. The theory shows that the steady-state, radially oriented induced electric field is zero everywhere inside the sphere for ramping coil current and highly attenuated for sinusoidal coil current. This allows the model to be extended to concentric spheres which have different electrical properties.


Prolonged retention of doubly labeled phosphatidylcholine in human plasma and erythrocytes after oral administration.

The plasma kinetics of a preparation of dilinoleoyl phosphatidylcholine (DLPC) specifically labeled with 3H in the choline moiety and with 14C in the 2-fatty acid (FA) were evaluated in six healthy volunteers after oral administration. Retention of both isotopes in plasma exceeded expectations, with a half-life in the elimination phase of 172.2 h for 3H and 69.7 h for 14C. Up to 60 d after administration, there were still significant levels of radioactivity present in plasma. The relative stability of the [14C]FA label was demonstrated by the retention for more than 12 h of an isotope ratio close to that of the compound administered. The 14C label of DLPC remained in position-2, as assessed by cleavage of plasma phospholipids with phospholipase A2. The [3H]choline label showed an early incorporation into high density lipoproteins and subsequently into low density lipoproteins (LDL); conversely, the 14C radioactivity was rapidly incorporated into triacylglycerols that were mainly associated with very low density lipoproteins. Radioactivity measurements revealed that both isotopes remained the longest time in LDL. In red blood cell (RBC) lipids, [3H]choline radioactivity accumulated over time, with a plateau after 48 h, whereas FA radioactivity accumulated more rapidly and was followed by a progressive decay. Analysis of the isotope ratio in these cells suggested an early incorporation of lyso products followed by rapid transfer of FA from plasma. The RBC maintained considerable radioactivity for a prolonged time, thus acting as a possible reservoir for the DLPC administered.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduction in triacylglycerol levels by fish oil correlates with free fatty acid levels in ad libitum fed rats.

Rats were fed (for 2 or 6 wk) purified diets containing lard (LD) or menhaden oil (MO) at two levels of dietary fat, i.e., at 11.5 and 20.8% of energy in the low fat (LF) and the medium fat (MF) diets, respectively. Following the diet period, rats were sacrificed after either an overnight fast or after uninterrupted ad libitum feeding. The studies were designed to investigate the dependence of our previously reported effects of MO, i.e. the reduction of plasma free fatty acid (FFA) levels and accumulation of hepatic triacylglycerols, on the dietary fat concentration and the nutritional state of the animal at the time of sacrifice. Reductions in plasma triacylglycerol and cholesterol levels in MO-fed relative to LD-fed rats were observed under all conditions. FFA levels were consistently reduced by MO-feeding at both dietary fat concentrations, but only when blood was sampled from ad libitum fed rats. Under these conditions there was a significant positive relationship between plasma FFA and triacylglycerol concentrations. Reduction in plasma FFA levels may be an additional mechanism associated with the triacylglycerol-lowering effect of fish oil (FO). The LF and MF MO diets caused a rise in plasma glucose levels with no significant change in insulin concentration, indicating that the reduction of FFA by MO was not related to changes in insulin concentration or insulin sensitivity. The MO diets had no effect on skeletal muscle or epididymal adipose tissue lipoprotein lipase activity, demonstrating that catabolism of triacylglycerol-rich lipoproteins contributes little, if any, to the MO-dependent reductions of plasma triacylglycerol and FFA.(ABSTRACT TRUNCATED AT 250 WORDS)


Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets.

The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0-16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0 + 14:0) or medium chain triglycerides (MCT, 8:0 + 10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oil vs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)


Headspace gas chromatography to determine human low density lipoprotein oxidation.

We previously described a rapid headspace gas chromatographic method for the determination of hexanal, an important decomposition product of n-6 polyunsaturated fatty acid (PUFA) peroxidation in rat liver samples and human red blood cell membranes. This method was applied to the measurement of Cu2+ catalyzed-oxidation of freshly prepared human low density lipoproteins (LDL) from 10 healthy adult volunteers. A twofold variation in oxidative susceptibility was found by this assay for hexanal and other volatiles. Hexanal values correlated significantly (P < 0.05) with total polyunsaturated fatty acid (PUFA), 18:2 and n-6 PUFA contents of LDL; but poorly with 20:4 and with vitamin E. Therefore, in addition to alpha-tocopherol, other endogenous antioxidants and factors may contribute to LDL's resistance to oxidation. This simple, rapid and sensitive method for oxidative susceptibility provides a useful component in the analysis of the prooxidant/antioxidant status of biological samples. The method is used routinely in our laboratories to determine specific peroxidation products of n-6 and n-3 PUFA.


Fluorescence assay of glucosylceramide glucosidase using NBD-cerebroside.

A sensitive fluorometric assay for glucocerebroside beta-glucosidase [Dinur, T., Grabowski, G.A., Desnick, R.J., and Gatt, S. (1984) Anal. Biochem. 136, 223-234] has been reexamined. It was found that the lipids containing the NBD moiety (12-[N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)] used for standardization of the assay are light-sensitive and that the yield of fluorescent light is very sensitive to the composition of the solvent used in the fluorometric measurement. Some protection against fading could be obtained by adding a free-radical trapping agent, SlowFade. The fading of the free NBD-acid, when used for standardization, could be prevented by adding ethanol to the solvent, but this reduced the fluorescence yield. It is recommended that some of the fluorescent substrate be enzymatically hydrolyzed completely to NBD-ceramide, which can be utilized as the standard without the need to add ethanol. A warning about enzyme reaction rate stability with time is given, with a suggestion for ensuring constancy of activity.


Heterogeneity of molecular weight and apolipoproteins in low density lipoproteins of healthy human males.

The molecular weights of five low density lipoprotein (LDL) subfractions from four normal healthy males were determined by analytic ultracentrifuge sedimentation equilibria. Protein content of each subfraction was determined by elemental CHN analysis, and weights of apoprotein peptides were calculated. Molecular weights in subfractions of increasing density were 2.92 +/- 0.26, 2.94 +/- 0.12, 2.68 +/- 0.09, 2.68 +/- 0.28 and 2.23 +/- 0.22 million Da, and protein weight percentages were 21.05, 21.04, 22.05, 23.10 and 29.10, in subfractions 1, 2, 3, 4 and 5, respectively. Total mean apoprotein weights for respective subfractions were 614 +/- 53, 621 +/- 45, 588 +/- 9, 637 +/- 83 and 645 +/- 62 KDa. In addition to a single apoprotein B-100 (apo B-100) peptide with a mean carbohydrate content of 7.1% and a molecular weight of 550 KDa per LDL particle, there may be one or more apoprotein E peptides of 34 KDa and/or apoprotein C-III of 9 KDa. In addition, subfractions 4 and 5 may contain 3-7% apolipoprotein (a). There is considerable heterogeneity among LDL subfractions as well as within the same fraction from different individuals. This heterogeneity may relate to differences in origin, metabolism and/or atherogenicity as a result of their content of apoproteins other than apo B-100.


Effects of a platelet-activating factor antagonist, CV-6209, on gastric mucosal lesions induced by ischemia-reperfusion.

Recent research was shown that oxygen-derived free radicals are involved in the pathogenesis of various diseases, including ischemia-reperfusion injury. We have also reported that oxygen-derived free radicals and lipid peroxidation may play an important role in gastric mucosal injury induced by ischemia-reperfusion. The hypoxanthine-xanthine oxidase system and neutrophils are considered important sources of oxygen-derived free radicals in this process. In recent years, it also has been shown that serum platelet-activating factor (PAF) levels increased during ischemia-reperfusion, and that induction of superoxide generation by neutrophils is one of the important biological effects of PAF. In the present study, we examined the effect of CV-6209, a specific PAF receptor antagonist, on gastric mucosal injury induced by ischemia-reperfusion, to shed some light on the possible involvement of PAF in such lesions. CV-6209 significantly attenuated the gastric mucosal injury induced by ischemia-reperfusion, and inhibited both an increase of thiobarbituric acid reactive substances and a decrease of alpha-tocopherol in gastric mucosa after ischemia-reperfusion. However, CV-6209 had no effect on gastric mucosal blood flow during ischemia-reperfusion. These results suggest that endogenous PAF may play an important role in gastric mucosal injury induced by ischemia-reperfusion, and that CV-6209 exerts its beneficial effect mainly by inhibiting neutrophil superoxide production induced by PAF.


The existence of a soluble plasmalogenase in guinea pig tissues.

The distribution of plasmalogenase for the hydrolysis of 1-alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmenylethanolamine) in the subcellular fractions of guinea pig tissues was examined. Plasmalogenase activity was found in high abundance in the cytosolic fractions of the brain and the heart. Assessment of microsomal marker enzyme activities in the cytosolic fraction revealed that plasmalogenase activity in the cytosol was not due to microsomal contaminations. The characteristics of the cytosolic plasmalogenase were very similar to the microsomal enzyme with respect to the pH profile of the reaction, the presence of divalent cations and Km values for plasmenylethanolamine. However, the cytosolic enzyme was slightly less stable at 55 degrees C than the microsomal enzyme. Cytosolic enzyme activity was eluted as a broad peak in Sepharose 6B chromatography with an average molecular weight of 250,000. Our results demonstrate that most of brain plasmalogenase activity is soluble which makes the brain cytosol an excellent source to initiate the purification of this enzyme.


Production of the Criegee ozonide during the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes.

It is likely that Criegee ozonides are formed in small amounts in the lungs of animals breathing ozone-containing air. This makes these compounds potential candidates to act as secondary toxins which relay the toxic effects of ozone deeper into lung tissue than ozone itself could penetrate. Therefore, we have determined the yields of Criegee ozonides from unsaturated lipids in liposomal systems as a model of the types of yields of Criegee ozonides that might be expected both in the lung lining fluid layer and in biological membranes. Ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes produced both cis- and trans-Criegee ozonides. These ozonides have been isolated by solid phase extraction and high-performance liquid chromatography of the ozonized lipid, and the products have been identified by two-dimensional 1H nuclear magnetic resonance. The combined yield of the cis- and trans-Criegee ozonides is 10.7 +/- 2.8% (avg. +/- SD, n = 7) with small unilamellar liposomes and 10.6 +/- 2.7% (n = 3) with large multilamellar liposomes. We had previously reported (Chem. Res. Toxicol. 5, 505-511, 1992) that ozonation of methyl oleate in sodium dodecylsulfate micelles also produces an 11% yield of the Criegee ozonides. Thus, ozonation in a variety of models gives about 11% of the Criegee ozonide, suggesting that these products also would be formed in small but significant amounts in the lungs of animals breathing polluted air. Further research on the pharmacokinetics and possible toxicity of the Criegee ozonides of fatty acids is suggested.


Kinetics of photoperoxidation of arachidonic acid: molecular mechanisms and effects of antioxidants.

The kinetics of photoperoxidation of [1-14C]arachidonic acid (20:4n-6) at 1.32 mM was studied either with the unsaturated fatty acid alone or in the presence of 10 microM of antioxidants and/or inhibitors of eicosanoid metabolism. The photosensitizer used was meso-tetraphenylporphine. The time-course of the reactions was followed by ultraviolet spectral analysis, thiobarbituric acid reactivity and high-performance liquid chromatographic analysis of aliquots sampled every 15 min during the 4 h of irradiation. The kinetics of photoperoxidation of 20:4n-6 can be divided into three main successive steps: (i) monohydroperoxidation, characterized by the appearance of conjugated diene patterns and monohydroperoxidized 20:4n-6; (ii) secondary oxidation characterized by polyoxygenated products such as dihydroperoxidized 20:4n-6 possessing conjugated triene patterns; and (iii) the disappearance of conjugated patterns and the oxidative cleavage of the products of the two first steps into aldehydic molecules reacting with thiobarbituric acid. During the first 90 min of irradiation, the mechanism of monohydroperoxidation (step one) is purely or predominantly type II photoperoxidation involving only singlet oxygen. This step was inhibited by beta-carotene and by BW755C (3-amino-1-[3-trifluoromethylphenyl]2-pyrazoline). In contrast, the reactions involved in the second and third steps were predominantly type I photoperoxidation involving radical mechanisms. These latter steps were inhibited by beta-carotene, BW755C, vitamin E and probucol. Indomethacin and 5,8,11,14-eicosatetraynoic acid did not alter 20:4n-6 photoperoxidation. This in vitro model of lipid photoperoxidation allows the screening of antioxidants in accordance with their singlet oxygen quenching and/or free radical scavenging properties.


Eicosapentaenoic acid at hypotriglyceridemic dose enhances the hepatic antioxidant defense in mice.

The effect of oral administration of purified (95%) eicosapentaenoic acid on serum lipids, hepatic peroxisomal enzymes, antioxidant enzymes and lipid peroxidation was compared with that of palmitic acid fed mice and corresponding controls. After 10 d, a dose of 1000 mg eicosapentaenoic acid per day/kg body weight lowered serum triglycerides by 45%, while no significant change in serum cholesterol level was noted in comparison to palmitic acid fed mice and controls. Hepatic acyl-CoA oxidase and catalase activities increased by 50% and 30%, respectively, in the eicosapentaenoic acid fed group. In addition, the hepatic reduced glutathione content and the activities of glutathione transferase, glutathione peroxidase and glutathione reductase, increased significantly during eicosapentaenoic acid treatment. The levels of hepatic lipid peroxides were lower after eicosapentaenoic acid feeding, while no significant change was noted in the palmitic acid fed mice when compared to the controls. Taken together, the present data demonstrate for the first time that at hypolipidemic doses eicosapentaenoic acid feeding i) enhances the hepatic antioxidant defense, and ii) does not cause a significant differential induction of the two peroxisomal enzymes, acyl-CoA oxidase and catalase, as was noted after administration of hypolipidemic peroxisome proliferating compounds, such as clofibrate in rodents.


Zinc deficiency in the rat alters the lipid composition of the erythrocyte membrane Triton shell.

The effect of dietary zinc deficiency on the lipid composition of the erythrocyte membrane Triton shell was determined. Weanling male Wistar rats were fed an egg white-based diet containing < 1.0 mg Zn/kg diet ad libitum. Control rats were either pair-fed or ad libitum-fed the basal diet supplemented with 100 mg Zn/kg diet. A Zn refed group was fed the -Zn diet until day 18 and then pair-fed the +Zn diet until day 21. Dietary Zn deficiency caused an increased cholesterol/phospholipid ratio in Triton shells compared to those from pair-fed controls. Zn deficiency caused a decreased double bond index of fatty acids in phosphatidylinositol (PI) and phosphatidylcholine (PC); there was a decreased proportion of 18:2n-6 and 22:4n-6 in PC and 20:4n-6 in PI as compared to that found in pair-fed controls. All glycerophospholipids that were retained in the shell had a lower double bond index and increased content of 16:0 and/or 18:0 relative to the phospholipid in the intact membrane.


Lipid composition of subcellular membranes from larvae and prepupae of Drosophila melanogaster.

Subcellular membranes were analyzed for their lipid composition and protein content at two developmental points representing the third instar wandering larvae and prepupal stages of Drosophila. At both stages, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were the major constituents with phosphatidylinositol (PI), phosphatidylserine (PS), diphosphatidylglycerol (DPG) and phosphatidic acid (PA) being relatively minor components. In total homogenates and in the nuclear-enriched fraction there was no significant difference in the phospholipid composition of the wandering larvae and prepupae. In mitochondria only a significant increase in the minor component PS was observed in the prepupae. In lysosomal membranes on the other hand, the relative abundance of the major components PE and PC increased in the prepupae although the molar ratios of the two lipids remained almost constant. The fatty acid composition of the phospholipids remained virtually unchanged in all of the fractions examined, including the lysosomes, and there was no evidence of lipid peroxidation. With regard to cellular degeneration and the involvement of lysosomes, we conclude that mechanisms other than gross modification of the lipid and/or lipid/protein ratio of their membranes are involved in the liberation of the acid phosphatase contents.


Free fatty acids inducing mouse lethal toxicity in lipid extracts of Engraulis japonica, the Japanese anchovy.

Mouse lethal toxicity was detected in the ether extract of Engraulis japonica (anchovy). The mouse toxicity of extracts was more potent from viscera than from other organs. Okadaic acid (C44H68O13) and dinophysistoxin (C45H70O13), lipophilic toxins derived from phytoplankton, which are usually considered to be the diarrhetic shellfish toxins, were not detected in the ether extract of ancovy. There occurred, however, two prominent peaks in high-performance liquid chromatography, which were identified as free eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The mouse toxicity observed correlated with the intensity of these two peaks. Toxicity was reduced considerably by pretreatment with Na2CO3. By quantitating EPA toxicity, it was concluded that the toxicity was not due to EPA only but also to DHA. The results indicate that substances in Japanese anchovy associated with mouse lethal toxicity include free polyunsaturated fatty acids, mainly EPA and DHA.


Palmitic acid enhances cholesterol gallstone incidence in Sasco hamsters fed cholesterol enriched diets.

In an established hamster model of cholesterol cholelithiasis, a semipurified lithogenic diet containing 4% butterfat and 0.3% cholesterol leads to the production of cholesterol gallstones in only 50-60% of animals after a 6-wk feeding period. The purpose of this study was to investigate whether gallstone incidence could be increased while feeding a nutritionally adequate diet of moderate cholesterol content. The semipurified lithogenic diet was modified as follows: (i) substitution of 1.2% palmitic acid for 4% butterfat, and (ii) varying the amount of dietary cholesterol from 0.0 to 0.3% with either butterfat or palmitic acid as the lipid component of the diet. Substitution of palmitic acid for butterfat produced a significantly higher incidence of cholesterol gallstones (94% vs. 53%). Palmitic acid also raised the incidence of gallstones when added to the 0.1% and 0.2% cholesterol diets as compared to butterfat: 0% vs. 44% and 50% vs. 81%, respectively. Gallstone incidence increased from 0% to nearly 100% when the cholesterol content of the palmitic acid diets was raised from 0.0% to 0.3%, indicating a dose response effect with respect to dietary cholesterol. Hamsters fed cholesterol-free diets did not form gallstones. Increased dietary cholesterol led to increased liver weight associated with a significant increase in liver cholesterol concentration. However, the palmitic acid groups had significantly lower liver cholesterol values than the corresponding butterfat groups. Serum and biliary cholesterol concentrations increased with increasing dietary cholesterol intake, but there were no differences between the butterfat and palmitic acid groups.(ABSTRACT TRUNCATED AT 250 WORDS)