Chemotherapy of advanced L1210 leukemia with platinum compounds in combination with other antitumor agents.

Six antitumor platinum compounds were used in combination with cyclophosphamide (CY) plus one of five other antitumor drugs in the treatment of advanced (Day 3) L1210 leukemia in (C57BL/6 X DBA/2)F1 mice. The combination of CY with a platinum compound yielded a collective cure rate of 24%; the addition of a third drug to the dual regimen increased the collective cure rate to 55%. The most effective drugs when used in combination with platinum compounds plus CY were, in increasing order of efficacy, 5-fluorouracil, hydroxyurea, and methotrexate. No toxic deaths occurred with any regimen at the dose levels used.


Regional blood flow, contractility and metabolism in early myocardial infarction.

The effects of occlusion of the left anterior descending coronary artery on a variety of metabolic parameters was examined in both infarcted and noninfarcted areas of the dog heart. These included mitochondrial performance, glycolysis, in vitro contractility, and regional myocardial blood flow. Measurements were made at 1 and 3 h after onset of ischemia. Regional coronary blood flow was measured in infarcted, noninfarcted and borderline regions using radioactive microspheres. Blood flow through the ischemic area was reduced by an average of 69% after 1 h of ischemia, and 75% after 3 h. After 3 h the subendocardium of the borderline region also revealed a significantly reduced blood flow. Mitochondria isolated from the ischemic region of the heart exhibited a substantial decrease in the rate of respiration (QO2), and minor reductions in the coupling between oxidative phosphorylation and electron transport (RCI), and in the amount of ADP phosphorylated per oxygen reduced (ADP:O ratio). Levels of hexose monophosphates were elevated 1 and 3 h after ischemia was initiated. At the same time, the concentration of fructose-1,6-diphosphate declined markedly, reflecting inhibition of glycolysis at the phosphofructokinase level. Concentrations of the adenosine phosphate moieties, as well as creatine phosphate, were reduced, while levels of free fatty acids were elevated in ischemic tissue. The in vitro contractility of glycerinated ischemic muscle fibers was also depressed. Significant changes were found in maximal tension development (P0), maximal rate of tension development (dp/dtmax), time to peak tension (t0), and shortening velocity at zero load (Vmax).


Effects of sympathetic blockade and splenectomy on cardiac output response to muscular work in dogs.

The effects of splenectomy and sympathetic blockade on cardiac output (Q) response to mild to moderate exercise were studied in chloralose-anesthetized vagotomized dogs during electrically-induced muscular work, which increased oxygen consumption (VO2) 4- to 5-fold. Splenectomy reduced the exercise factor (deltaQ/deltaVO2 ratio) from 5.86 +/- 0.43 (SE) to 3.30 +/- 0.34 (p less than 0.001), while left nephrectomy had no effect. The exercise factor was not affected by beta-adrenoceptor blockade produced by propranolol or practolol, but was reduced by mecamylamine. The spleen did not increase cardiac output by displacing blood into the general circulation because pulmonary artery wedge pressure did not change during exercise in normal dogs. Furthermore, cardiac output was increased 35 +/- 6% after intraportal infusion of splenic venous blood obtained during exercise, whereas arterial blood infusion increased cardiac output only 10%. We conclude that the cardiac output rise during exercise in part is caused by the inotropic action of a splenic noncatecholamine substance, which is released by sympathetic stimulation.


Bilateral bundle branch block. Right bundle branch block associated with left anterior fascicular block.

This report describes the clinical and electrocardiographic features in 30 cases of complete right bundle branch block associated with a block of the anterior fascicle of the left bundle branch, 7 of which also featured a block of the posterior fascicle of the left bundle branch (trifascicular block). The majority of the patients suffered from coronary atherosclerotic heart disease and/or hypertensive heart disease. Complete right bundle branch block associated with fascicular block of the left bundle branch constitutes a special electrocardiographic pattern. The prognosis of the patients presenting this pattern is poor, since it may develop into trifascicular block, i.e., complete atrioventricular block, often necessitating the implantation of artificial pacemakers.


Postexercise systolic time intervals in the midsystolic click syndrome.

Postexercise systolic time intervals (STI) were measured in ten patients (PMV group) with auscultatory evidence of the midsystolic click syndrome (i.e. one or more systolic nonejection clicks alone or in association with the late systolic murmur), and compared to eight age-matched volunteers (control group) with no evidence of heart disease. Following measurement of supine STIs, the subjects pedalled an upright bicycle ergometer at progressive work loads until a target heart rate (HR) representing 85% of the age-adjusted maximum was attained, or an abnormal end point was noted. Immediately postexercise, a repeat measurement of STIs, was obtained. A shortened or unchanged postexercise left ventricular ejection time corrected for HR (deltaLVETc) and a marked shortening of total electromechanical systole after exercise (deltaQS2c) constituted a normal STI response to stress testing and was noted in all control subjects. All of the PMV group exhibited evidence of left ventricular dysfunction characterized by a prolonged deltaLVETc. It is concluded that an abnormal STI response to exercise consistent with left ventricular dysfunction can be demonstrated in patients with prolapse of the mitral valve by the response of the STI.


Aspects of cardiac venous flow measured by the continuous infusion thermodilution technique.

The continuous infusion thermodilution method for the measurement of cardiac venous blood flow was investigated in 26 patients with angina pectoris. In 10 patients, the correlation coefficients for duplicate flow measurements within 1 min were 0.98 for the coronary sinus (CS) and 0.99 for the great cardiac vein (GCV), with a variation in relation to mean flow of 3.3 and 3.5%, respectively. The average CS drainage in 16 patients amounted to 126 ml/min with the GCV contributing 57% of the total and all other veins (OV) draining into the sinus 43%. Submaximal atrial pacing led to a significant increase in flow in all veins. The mean increase in flow per heart beat was 1.41 ml in the CS, 0.93 ml in the GCV, and 0.58 ml in the OV. The increase in flow per unit (1 X 10(-3) mm Hg - beats) heart rate times blood pressure product was 9.18, 6.97 and 4.71 ml, respectively. The method is suitable for the measurement of rapid changes in total and regional left ventricular blood flow under different conditions. For longer studies spontaneous changes in parameters governing myocardial oxygen demand must be taken into consideration.


Ventilatory effects on pulmonary vascular inflow and outflow patterns.

Ventilation of an isolated lung lobe modifies the rate of inflow into its pulmonary artery (Murao and Rodbard, 1971). The present studies show that ventilation also influences the rate of outflow from the pulmonary vein in a manner which differs significantly from the effects on the rate of inflow into the pulmonary artery. Since this difference between instantaneous inflow and outflow rates affects the calculation of vascular conductance (resistance) and its interpretation we have compared and analysed the effects of ventilation on simultaneous flow patterns in the pulmonary artery and vein.


The effect on atrial and ventricular intracellular potentials, and other pharmacological actions of L9146, a non-halogenated benzo(b)thiophene related to amiodarone.

L9146 was synthesised in the hope of eliminating the unwanted side-effects of amiodarone which has been shown to be effective in the control of atrial fibrillation, flutter, and in pre-excitation syndromes such as Wolff-Parkinson-White syndrome. L9146 has pharmacological and electrophysiological effects similar to those of amiodarone. It is an antagonist of both alpha and beta adrenoceptor-mediated cardiovascular effects of a noncompetitive type. It lowers vascular resistance briefly, and causes a longer lasting bradycardia. It moderately reduces the maximum rate of depolarisation (MRD), conduction velocity, and totally suppresses ventricular pacemakers activated by high doses of isoprenaline. In addition, L9146 greatly prolongs action potential duration (APD) in atrial and ventricular muscle. In normal ventricular conducting tissue the action potential duration (APD) is shorter in the bundle of His than in the false tendons, and shorter still in the ventricular muscle. L9146 lengthened APD throughout, but particularly in the proximal portion, and even more in the muscle, so that APD became uniform. The decrement of conduction of premature action potentials was increased to the point at which slowly conducting premature AP's were eliminated altogether.


Free fatty acids and arrhythmias following acute coronary artery occlusion in pigs.

The arrhythmogenic potential of elevated serum free fatty acids (FFA) was investigated in closed-chest pigs following acute coronary artery occlusion. Animals both with and without ventricular irritability before the FFA rise were studied. No significant increase in PVC frequency occurred and only 1 out of 17 animals developed ventricular fibrillation in the 60 min following acute FFA elevation. In this situation, FFA did not significantly influence the appearance of arrhythmias.


Postnatal maturation of noradrenaline uptake and release in cat papillary muscles.

Catecholamine uptake and release have been studied in isolated right ventricular papillary muscles from kittens aged less than 24 hours, 16 to 18 days and 28 to 32 days. Under the age of 24 h catecholamine uptake (uptake I) does not appear to be functioning and at this age there is a significantly lower response to tyramine. These results suggest that myocardial sympathetic innervation continues to mature, in the cat, after birth.


On the relationship between action potential duration and tension in cat papillary muscle.

Tension and action potentials have been measured simultaneously from isolated cat papillary muscles. Two groups of experiments are described. In the first group, the external conditions under which the muscle contracted were changed. Specifically, stimulation rate, extra-cellular [Ca++], extracellular [Na++] were altered, and adrenaline was added to the bathing fluid. A tendency for given levels of tension to be accompanied by action potentials of constant duration is demonstrated under some of these conditions. In the second group of experiments, tension and action potentials were recorded following some change in external conditions; specifically, after a long rest, after a change in muscle length, and after the muscle had been set up in the experimental apparatus (the 'running-in' period). In the period that followed each of these interventions, peak tension increased substantially over at least several minutes but all external conditions (for example, temperature, muscle length, stimulation rate, and composition of the bathing fluid) remained constant. In each of these three situations tension increased but in one case the action potential duration increased, in another it decreased, and in the third it was unchanged. It is concluded that change in action potential durations do not necessarily make an important contribution to the changes in tension of papillary muscles.


Failure of an antagonist of histamine--chlorpheniramine--to modify the pulmonary vascular response to hypoxia in chronic bronchitis.

Experimental evidence from animals suggests that the response of the pulmonary circulation to hypoxia is mediated by histamine. In 3 patients with chronic bronchitis the pulmonary vascular response to hypoxia was measured before and after administration of chlorpheniramine, a competitive antagonist of histamine. No convincing evidence was obtained of a reduction in the size of the response to hypoxia.


Influence of viability on canine allograft heart value structure and function.

A study was undertaken to determine whether, in antibiotic sterilised and stored valves, the state of preimplantation leaflet viability could be shown to influence valve structure and function following isotopic allotransplantation in dogs. Fourteen viable and 12 nonviable valves were assessed after periods of up to 8 weeks' implantation. Assessment of valve structure was made macroscopically with measurement of leaflet surface areas, and microscopically. Pressure measurements were made across the allografted valve both at insertion and at removal. The results of this study indicate that preimplantation viability results in gross valve leaflet distortion and shrinkage with consequent loss of function. Nonviable valves, in contrast, showed minimal alteration in valve dimensions with retention of normal function. These findings have considerable implications in the preparation and clinical use of allograft heart valves.


Platelets and the vascular responses to arachidonic acid in dogs.

Platelets are rich in components of the prostaglandin synthetase system which converts arachidonic acid into vasoactive and platelet-active prostanoate and nonprostanoate compounds. Repeated injections of arachidonic acid in dogs cause hypotension of reproducible magnitude and lower circulating platelet counts with each injection. However, the circulatory response to injected arachidonic acid was unchanged when platelet-poor blood was exchanged in dogs. Moreover, in the hind limb preparation and the isolated lung lobe, the vasoactive responses to arachidonic acid were indistinguishable whether perfused with whole blood or an artificial perfusate. the vascular responses to arachidonic acid do not appear dependent on the presence of platelets.


Direct effect of acebutolol on force generation in immature and adult myocardium.

The effect of acebutolol on active isometric force generation has been studied in isolated papillary muscle preparations from adult cats and kittens less than 24 h old. Statistically significant reduction in active force occurred at a concentration of 0.27 mmol-litre-1 in the adult preparations and at 1.34 mmol-litre-1 in the infant ones. At 2.86 mmol-litre-1 active force had fallen to 43.4%+/-2.2 (SEM) of the control value in the adults and to 52.4%+/-3.3(SEM) in the infants. These results suggest that the infant myocardium is no more sensitive to the negative inotropic effect of acebutolol than is the adult myocardium.


Changes of the kinetics of calcium washout from dog heart after ischaemia.

The kinetics of myocardial calcium washout using a calcium free perfusion were studied in controls and animals after a short period of ischaemia. A significantly higher rate for k3 was found after ischaemia. This may represent a greater lability of membrane-bound calcium.


Bedside measurement of systolic and diastolic time intervals using the stethometer.

Using a modified electronic stethoscope, a simple visual method has been developed for bedside estimation of systolic and diastolic intervals. This has been applied to the measurement of S1-S2, LVET, and 2-OS as well as the intervals produced by prosthetic valve sounds.


The effect of a single injection of hydroxyurea on cell population kinetics in the small bowel mucosa of the rat.

The effect of a single injection of hydroxyurea (HU) on cell population kinetics in the jejunal crypt of the rat was studied using autoradiography with tritiated thymidine and metaphase arrest with vincristine. HU appeared to act selectively on cells in the S phase producing inhibition of DNA synthesis and cell death. The deficit in proliferating cells was made good by a decrease in cell cycle time and an increase in growth fraction. Particular attention was paid to the basal, slowly cycling (and possibly clonogenic) crypt cells; early in the recovery sequence an increase in cell production rate was found in the base of the crypt. It is proposed that basal crypt cells, having survived cycle-specific insult because of long cell cycle times, proceed to repopulated the depleted proliferative compartment.


The effects of red blood cell extracts on the proliferation of erythrocyte precursor cells, in vivo.

Saline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio-iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 microgram per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cells proliferation completely but simply lengthens the cell cycle, mainly by increasing the GI phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non-toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.


Specific inhibition of cell proliferation in the mouse intestine by an aqueous extract of rabbit small intestine.

An aqueous extract was prepared from the mucosa of rabbit small intestine by homogenization and centrifugation at 105,000 g. After precipitation with ammonium sulfate, the 0-50 fraction (F1) and the supernatant (F2) were collected, dialysed against a phosphate buffer and tested on rats in vitro and mice in vivo. The F1 fraction was found to inhibit thymidine incorporation into rat intestinal DNA in vitro, but this effect was not found to be tissue specific (liver, kidney). Two hours after a single injection of F1 (10 mg protein content), the uptake of tritiated thymidine was decreased in jejunal and colonic DNA in mice. This effect was maximal between 2 and 4 hr and totally reversible after 7 hr; this effect was found in neither the kidney nor the testis. A slowing of cellular migration was also noticed in the jejunum and the colon. Conversely, the F2 fraction did not inhibit the synthesis of jejunal and colonic DNA either in vitro or in vivo. Our results suggest that the F1 fraction of the aqueous extract of rabbit small intestine contains one or more substances which may act either on intestinal DNA synthesis or on the GI--S transition of the cellular cycle in the mouse intestine. This reversible and specific intestinal action appears to inhibit cell proliferation and presents several of the characteristics defining a chalone.


Sexual dimorphism in the gills of the spawning river lamprey, Lampetra fluviatilis L.

Two types of mitochondria-rich cells were found in the interplatelet areas of the gills of sexually mature, male river lampreys. Type 1 cells (previolsy referred to as "male glandular cells") showed some ultrastructural characteristics in common with ion-transporting cells but were readily distinguished by large lipid structures with electron-lucent centres. Type 2 cells were found to be identical to the presumed ion-uptake cells during other stenohaline freshwater phases of the animal's life history. In the sexually mature female, only Type 2 cells were positively identified. This sexual dimorphism in gill structure is discussed in relation to the possible functions of the lamprey gill, with particular reference to ionic regulation.


Cytochemical duality of neurosecretory material in the hypothalamo-posthypophysial system of the rat as related to hormonal content.

Cytochemical methods using silver proteinate, silver methenamine an potassium ferrocyanide + OsO4 for ultrastructural detection of glycoproteins allow, in the posthypophysis and the magnocellular nuclei of the rat, differentiation of two types of fibres and neurons: one type containing negative granules with a homogenous content of low electron density, the second type containing granules which demonstrate a ring shaped deposit either of silver or of potassium ferrocyanide-osmium complex, likely to be related to a glycoprotein component. The difference between these two types is increased by prestaining "en bloc" with uranyl acetate before the silver proteinate reaction. A similar investigation was carried out on the vasopressin deficient Brattleboro rat; the neurosecretory material, present in some endings and neurons only, is of the nonreactive type, so that it appears justified to correlate the reactivity of granules with vasopressin, consequently to distinguish neurones and fibres containing vasopressin from those in which oxytocin is quantitatively the main hormonal peptide. This conclusion is strongly supported by the fact that percentages of reactive and negative endings, as determined on this basis in the posthypophysis of normal rats from two different strains, are in good agreement with biochemical data reported in the literature.


Myogenesis and contraction in the early embryonic heart of the rainbow trout. An electron microscopic study.

Myogenesis in the embryonic heart of the rainbow trout, Salmo gairdneri (Rich.), was investigated electron microscopically from the 29th to the 41st somite stage. Thick and thin myofilaments are formed simultaneously as well as precursors of Z-lines, to which the thin filaments are attached. The genesis of filaments takes place in the region around the intracellular yolk droplets. The first myofibrils appear by the 33rd somite stage, probably formed by a mechanism of self-assembly in which the binding sites of actin and myosin participate. A- and I-bands do not develop before the 38th osmite stage. The contraction already begins during the 33rd somite stage in the middle of the tubular heart. Gradually, the peristaltic waves spread increasingly to other parts of the heart. In the 41st somite stage the entire heart is contractile and all myocytes contain myofibrils.


Immunohistochemical demonstration of contractile proteins in astrocytes, marginal glial and ependymal cells in rat diencephalon.

Actin and myosin were located in astrocytes, marginal glial and ependymal cells in rat diencephalon by using antibodies against highly purified chicken gizzard actin and myosin. On the basis of these findings it is suggested that glial cell motility in vovo and in vitro is due to the presence of an intracellular actin/myosin system.


Amino acid transport in the rat exocrine pancreas. I. Transport of neutral amino acids and their utilization in protein synthesis.

The transport and utilization of three neutral amino acids in protein synthesis was studied using isolated pancreatic lobules in vitro. The significance of the extracellular and intracellular amino acid pool in this process was analyzed removing the extracellular pool (labeled by inulin) by a cold-wash procedure. This was especially useful in short-term experiments. Double-labeling experiments indicated a predominant utilization of the intracellular amino acid pool during protein synthesis. The advantage of isolated pancreatic lobule preparations compared to tissue fragments or slices was emphasized by fine structural studies. Using freeze-etching techniques on the same preparations, differences in the distribution of membrane particles between luminal and  lateral plasma membranes described earlier were confirmed, as well as the abundant occurrence of gap junctions on both membrane faces.


A cytoarchitectonic study of the hypothalamus of the lizard, Calotes versicolor.

The hypothalamic nuclei of the lizard, Calotes versicolor, can be broadly divided into "AF-positive" and "AF-negative". The AF-positive cell complexes include the nucleus supraopticus, nucleus paraventricularis, and a few interconnecting bridge cells. In addition, some AF-positive neurones are also observed in the median eminence. As many as 15 AF-negative nuclei-like accumulations of nerve cells can be identified in the hypothalamus. The nucleus periventricularis hypothalami of earlier authors is subdivided into eight circumscribed neuronal complexes. In addition, a few AF-negative nuclei, e.g. nucleus subfornicalis, nucleus ventralis tuberis, nucleus med. recessus infundibuli, nucleus lat. recessus infundibuli and nucleus praemamillaris, are regarded for the first time as anatomical entities. The distribution of the hypothalamic nuclei and their cytoarchitectonic features are described  at the light microscopical level. An attempt has been made to interprete the nuclei identified in the present study on a comparative and phylogenetic basis.


Mitochondria-rich (chloride) cells in the gill epithelia from four species of stenohaline fresh water  teleosts.

The mitochondria-rich (chloride) cells have been found to be present in the gill epithelia of four species of stenohaline fresh water teleosts. The cytoplasm of these chloride cells contains an extensive network of cytoplasmic tubules which communicate with intercellular spaces bordering the lateral and basal cell surfaces. Numerous vesicles with fairly electron-dense interiors are also present in the apical cytoplasm of chloride cells. The apical surface of a chloride cell forms an apical pit, but the lumen of the  pit does not appear to be in continuity with the interior of the apical vesicles and tubules inside the cell. When Carassius auratus were kept in 100, 200, 300, and 400 mOsm-diluted sea water for a month, no appreciable changes occurred in the number and fine structure of the chloride cells, except for a dilation of the apical vesicles and a slight decrease in diameter of the cytoplasmic tubules in these cells in the fishes kept in 300 and 400 mOsm. These results suggest that chloride cells may be a rather common occurrence in the gill epithelia of stenohaline fresh water teleosts, and may function in ion transport in these fishes in fresh water environments.


Effect of neonatal sympathectomy on the postnatal differentiation of the submandibular gland of the rat.

Right superior cervical sympathectomy was performed in one-day old rats. This operation had a small but definite effect on the postnatal development of the submandibular gland. The gland on the sympathectomized side weighed less and contained smaller amounts of DNA, RNA and protein than the contralateral intact gland. The postnatal development of acinar cells and granular convoluted ductal cells was retarded in the sympathectomized gland. The acinar cells which differentiated after the ganglionectomy were smaller than those in the contralateral intact gland and were filled with secretory granules but devoid of basal basophilia. The rate of cellular proliferation in the sympathectomized gland was, however, similar to that intact gland at various ages studied.


Changes in the secretory activity of the glandular lobe of the corpus cardiacum of Locusta migratoria induced by flight. A quantitative electron microscopic study.

The glandular lobe of the corpus cardiacum of Locusta migratoria is characterized by the presence of one type of secretory cells containing secretory granules with a diameter of 2000-3000 A, and of axons with small granules (diameter 950 A). The axons form synaptic contacts with the cells. The secretory products of the glandular cell are released by exocytosis in the gland proper. In the axon terminals, release is indicated by the presence of synaptic vesicles and omega-shaped indentations. In order to study possible changes in the secretory activity of the gland during flight, three groups of locusts were studied with quantitative electron microscopical methods, i.e., resting insects, having flown for 5 min (short flight, SF), and insects after prolonged flight (PF, 60 min). After flight, greater secretory activity of the glandular cells is indicated by a marked increase in the number of exocytotic pits in SF and PF insects, by an enlarged nuclear volume as well as an increased amount of secretory products in the Golgi cisterns of PF animals. Flight also causes greater release activity in the axon terminals. From these results it is concluded that an intrinsic hormone, apparently the adipokinetic hormone, is released from the glandular lobe and regulates the substrate supply from the fat body during flight. It is suggested that the secretory activity of the glandular cells is controlled by the axon terminals on these cells.


Spermatogenesis revisited. III. The course of spermatogenesis in a male-sterile pink-eyed mutant type in the mouse.

Male mice homozygous for the recessive p-locus allele ps are sterile. Spermatogenesis is normal through the completion of meiosis, but is abnormal from the Golgi phase of spermiogenesis on. During acrosome formation various abnormalities appear, ranging from atypical Golgiacrosome complexes to multiple acrosome "implantation" sites on the spermatid nuclei. In many developing acrosomal caps the distribution of acrosomal material is irregular. During the nuclear elongation phase, bundles of microtubules oriented parallel to the manchette have been seen lying in cylindrical invaginations of some spermatid nuclei. In later spermatids, chromatin condensation appears to proceed normally but may be unduly delayed in reaching completion. These various perturbations give rise to a wide spectrum of abnormal spermatozoa ranging from spermatozoa with heads of near-normal morphology to highly bizarre heads which have lost their chromatin. Sperm flagellar ultrastructure is normal and all sperm tails; even those devoid of recognizable heads, are highly motile. These findings support the view that the development of the sperm head is under the control of a group of genes distinct from those mediating events involved in flagella development.


Spermatogenesis revisited. IV. Abnormal spermiogenesis in mice homozygous for another male-sterility-inducing mutation, hpy (hydrocephalic-polydactyl).

Gametogenesis is normal through meiosis and the earliest phases of spermiogenesis in male-sterile mice homozygous for the recessive, pleiotropic, mutation hpy (hydrocephalic-polydactyl). However, structurally complete sperm flagella were not encountered. Instead partially assembled axonemal structures and/or poorly organized aggregates of other tail components (mitochondria, outer coarse fibers) were seen at the posterior poles of nuclei in older spermatids. The ultrastructure of centrioles in spermatids was normal, but that of axonemes associated with them was not. These findings suggest that the observed flagella dysgenesis results from defects in assembly rather than from defective intiation centers. Released "gameters" usually consisted of ditorted nuclei and associated acrosome enclosed in a relatively close fitting plasma membrane. Perturbations of sperm head development were also encountered; they included extreme nuclear elongation, and distortion of the acrosome and underlying nuclear material by impushings of finger-like processes of Sertoli cells. It is believed that sperm head anomalies are secondary consequences of the mutant condition. The findings support the view that the hpy locus represents one of a number of genes primarily involved in the mediation of flagella development.


The ultrastructure of the sinus gland of the crayfish Astacus leptodactylus (Nordmann).

An ultrastructural study of the sinus gland of the crayfish Astacus leptodactylus demonstrates that this gland is mainly composed of glial cells, axons and axon terminals. On the basis of the size, shape and electron density of the neurosecretory granules, we could distinguish five different types of axon terminals.


Some morphogenetic features of the adenohypophysical primordium of early Xenopus laevis tadpoles.

The adenohypophyses of Xenopus laevis tadpoles at developmental stages 20 to 46 (Nieuwkoop and Faber, 1956) were studied. From its first appearance at about stage 20 to 21, the adenohypophysial primordium passes through four morphogenetic phases, each characterized by internal events. The first phase (stages 20 to about 33/34) is characterized by extensive proliferation of the primordium. During the second phase (stages 33/34 to about 37/38), the growth of the primordium is arrested. This arrest coincides with the attainment of secretory function. The primordium is claviform in shape at these stages. The third phase, roughly stage 39, is characterized by a thorough reorganization of the adenohypophysial cells, leading to the formation of the pars distalis and pars intermedia. The shape of the primordium changes, and its volume tmeporarily increases. The last phase is characterized by the organization of the pars distalis cells into cell cords which possibly demonstrate a functional relation to a specialized region (the "hilus") of the adenohypophysis-brain interspace.


The membrane systems of the cardiac muscle cell of Euchaeta norvegica Boeck (crustacea, copepoda).

The membrane systems of the cardiac muscle cell of the copepod Euchaeta norvegica Boeck are described. The heart wall, which is between 0.12 and 1.36 micrometer thick, consists of an epicardium and a single layer of muscle cells. Invaginations of the sarcolemma forming transverse tubules have been found at all levels of the sarcomere with the exception of the H-band level. The longitudinal tubules of the same system are closely associated with the sarcoplasmic reticulum to form interior couplings at the A-I level of the sarcomere. Triadic couplings at the Z band level were not seen in E. norvegica, but peripheral couplings were demonstrated. Nex-uses were found in the intercalated discs.


Ultrastructure of the myocardial cell and its membrane systems in the adult fly Calliphora erythrocephala (insecta: diptera).

Calliphora erythrocephala has cross-striated cardiac muscle cells with A, I and Z-bands. The diameters of the myosin and actin filaments are 200-250 A and 85 A respectively and the length of the myosin filaments (A-band) is approximately 1.5 micron. Usually 8-10 actin filaments surround each myosin filament. The myocardial cells show a well-developed membrane system and interior couplings. A perforated sheet of SR envelopes the myofibrils at the A-band, dilates into flattened cisternae at both A-I band levels before it merges into a three-dimensional net-work between the actin filaments of the I-bands and between the dense bodies of the discontinuous Z-discs. The T-system consists of broad flattened tubules running between the myofibrils at the A-I band levels forming dyads with the SR-cisternae. Longitudinal connections between the transverse (T-) tubules often occur. It is suggested that this well-developed SR may be an adaptation to facilitate a rapid contraction/relaxation frequency by an effective Ca2+ uptake.


Effect of anabolic steroids on rat heart muscle cells. I. Intermediate filaments.

Long-term treatment of female rats with the anabolic steroid hormone Methandrostenolone results in a conspicuous increase of intermediate sized, nonmyofibrillar filaments in muscle cells of the left cardiac ventricle, as revealed by electron microscopy. These filaments, measuring 70 - 110 A in diameter, form a characteristic network at the Z-level of the sarcomere, either encircling or penetrating the Z-bands, and appear to insert into the nuclear membrane. The T-system is accompanied by the filaments adjacent to the site of the couplings. Here they are attached to subsarcolemmal electron-dense patches, which may be Z-line precursor material. The filaments may function as a cytoskeleton, to provide passive support in the mechanism of contraction and to mediate nucleo-sarcolemmal and nucleo-myofibrillar exchange.


An ultrastructural study of the musculature of the pond snail Lymnaea stagnalis (l.).

The ultrastructure of the musculature of Lymnaea stagnalis was studied. Each of the six muscle systems of the body wall, previously distinguished in an anatomical study, has its own type of smooth muscle, characterised by the size and number of the myofilaments, number of mitochondria and distribution of smooth endoplasmic reticulum. The visceral musculature comprises both smooth and striated muscle. Cross-striated muscle is found in the heart and proximal aorta, obliquely striated muscle in the buccal mass, gizzard and vas deferens. Myofibroblasts and myoendothelial cells were also distinguished. On the basis of the observations it is concluded that striated muscles in L. stagnalis contract and relax more rapidly and have a higher endurance than smooth muscles, but that the latter can contract over a wider range. Among smooth muscles the head retractor muscle contracts most rapidly, the shell muscle is most powerful and the diagonal muscle is slow to contract but has a relatively high endurance. The latter muscle, together with the horizontal foot muscle, plays a major role in maintenance of the hydrostatic skeleton. A model for the organisation of the smooth muscles is deduced from the ultrastructural observations. It implies that the myosin-paramyosin filaments change their actin filament partners during contraction. This agrees with a model deduced for other smooth muscles on the basis of physiological experiments and X-ray diffraction analysis.


Fine structure of rabbit ear chondrocytes in vitro and after autotransplantation.

Chondrocytes were isolated enzymatically from rabbit ear cartilage, grown in vitro or as autotransplants for 1, 2 or 5 weeks and then examined by transmission electron microscopy. A confluent monolayer formed rapidly in vitro and the cells later grew in multiple overlapping layers, producing thick sheets of cartilaginous tissue. The cells retained a normal structure throughout the period of observation and, like the chondrocytes in intact cartilage, showed numerous microfilaments, and extensive granular endoplasmic reticulum and a prominent Golgi complex. Large amounts of intercellular matrix were laid down in vitro consisting of thin collagen fibrils, small rounded or polygonal granules believed to represent proteoglycans and patches and fibres of elastin. Chondrocytes in intramuscular autotransplants reconstituted an elastic cartilage. The exogenous origin of the cells in the transplants was verified by labeling of the lysosomes by exposure of the cells to colloidal thorium dioxide particles prior to injection. Structurally, the cells and the matrix of the transplants conformed to the above description. Accumulations of elastin-like material were sometimes observed in the Golgi vacuoles of the cells. Extracellularly, such conglomerates aggregated in connection with bundles of microfibrils, building up mature elastic fibres with a dense amorphous structure. The culture and transplant systems characterized here provide suitable experimental models for studies on development, growth and aging of elastic cartilage, including various aspects of the formation and turnover of elastic fibres and other macromolecular matrix components.


Material transport within specialised ciliary shafts on Rhabdopleura zooids.

The surface of the Rhabdopleura zooid is ciliated. The cilia of the cephalic shield and tentacles have paddle-like swellings of the shaft. These swellings are usually about 0.6-1 micron in diameter and most frequently found in the distal 1-2 micron of the ciliary shaft. Others are found in other positions along the length of the cilium and it is suggested that at least some of these swellings represent material transport within the cilium. Paddle shaped cilia are probably more efficient than normal cilia in moving water and food particles. If these cilia are involved in the building of the tubular coenecium then their distribution suggests that the tentacles as well as the cephalic shield are actively involved in tube building.


Quantitative electron microscopic analysis of the epithelium of normal human alveolar mucosa.

The epithelium of normal human alveolar mucosa originating from the anterior vestibulum was subjected to stereologic analysis. Eight biopsies were collected half-way between the muco gingival junction and the vestibular fornix from 20 to 50 year-old females, and processed for light and electron microscopy. At two levels of magnification, electron micrographs were sampled from four artificially selected strata in regions of epithelial ridges. Stereologic point counting based on a computer-aided system for analyzing stratified epithelia served for examining a total of about 860 electron micrographs. The alveolar epithelium was 0.26 mm thick, occasionally interdigitated by short, slender connective tissue papillae, and consisted of (1) a narrow basal and suprabasal, and (2) a broad spinous and surface compartment. It displayed a differentiation pattern which, in most subjects studied, was similar to that of normal human buccal epithelium, however, on the average, produced less mature surface cells. This pattern was expressed mainly by a density increase of cytoplasmic filaments (98 A in diameter), a concomitant decrease of the cytoplasmic ground substance, the formation of dark-cored membrane coating granules, and invividually variable amounts of glycogen deposition. In some subjects, a mixed differentiation pattern was found. The structural organization of alveolar epithelium, in analogy to cheek epithelium, was compatible with the function of distensibility.


The effect of ecdysone on the fat body cells of the penultimate larvae of Mamestra brassicae.

The capability of beta-ecdysterone to induce autophagocytosis in the fat body cells of penultimate larvae of Mamestra brassicae was investigated both in vivo and in vitro. The hormone proved ineffective when applied for 3 h on the first 3 days of the instar, but it induced the formation of autophagic vacuoles on the 4th day (24 h before ecdysis). This effect became more pronounced when the hormone was administered 10 h before ecdysis. Cells incubated in vitro reacted to ecdysterone more sensitively than cells of similar age treated in vivo. It was concluded that the responsiveness of the fat body cells to ecdysterone as evaluated on the basis of autophagy depends on the age of the larvae. The increased sensitivity of the cells to ecdysterone at the end of the penultimate stage may be related to the decrease of juvenile hormone titre during this period.


Left ventricular endomycardial biopsy. I: description and evaluation of the technique.

The results of left ventricular endomyocardial biopsy by means of a long sheath technique in 154 patients are reported. The risks of left ventricular biopsy are those of left heart catheterisation. In 30 of these patients the results of left and right ventricular biopsy were compared, and in further 10 patients the right ventricle only was biopsied. Biopsy from the left ventricle carries less risk of cardiac perforation, gives a higher incidence of successful biopsy, and with the exception of hypertrophic obstructive cardiomyopathy yields more diagnostic information.


Left ventricular endomyocardial biopsy. II: the value of light microscopy.

Histological sections of left ventricular endomyocardial biopsies have been examined by light microscopy. The biopsies were taken from patients with congestive, hypertrophic, or restrictive cardiomyopathy and from patients with either aortic stenosis or regurgitation. In congestive cardiomyopathy no specific features were found and similar abnormalities were seen in aortic valve disease. In only one of six cases of asymmetric septal hypertrophy were the characteristic histological appearances noted. In four out of five patients with a restrictive type of cardiomyopathy, amyloid was demonstrated. The muscle fibres in aortic stenosis had a greater cross-sectional area than those in aortic regurgitation. A greater degree of fibrosis was present in aortic stenosis than in aortic regurgitation. In aortic stenosis the amount of fibrous tissue was inversely related to function.


A quantitative method for determining angiographic jet energy forces and their dissipation: theoretic and practical implications.

Jets emanating from the exit holes of cardiac catheters during angiographic injections are theoretically capable of producing severe localized cardiovascular trauma. We adopted a fluid mechanical model of an axially  symmetric jet to define these energy forces quantitatively, especially as they would occur in the clinical setting. During angiographic injection at all catheter flow rates used clinically, the jet emanating from the exit hole was always turbulent. The physical characteristics of the turbulent jet penetration into the  intravascular blood fell upon a universal curve independent of the jet Reynolds number. This curve, never previously described, allows ready calculation of hydraulic energy dissipation for any catheter of known length and lumen size. The diameter of the catheter exit orifice has a greater effect than injection flow rate on decreasing jet penetration. These results provide useful guidelines for reducing trauma during routine angiography.


Knotting of a flow-directed catheter about a cardiac structure.

An instance of knotting of a flow-directed catheter about an intracardiac structure, presumably part of the tricuspid valve apparatus, is described. Because of the patient's severe pulmonary disease, cardiac surgery to remove the catheter was contraindicated. The central portion of the catheter was allowed to remain in situ, without apparent ill effects over a 16 month period.


A simple, inexpensive technique to permit the half-axial projection in laboratories with single plane cineangiography.

A simple inexpensive modification to permit x-ray beam angulation of a cineradiographic system consisting of a ceiling-suspended image intensifier and an under-the-table x-ray tube is described. This has permitted the incorporation of the half-axial projection into the routine evaluation of the proximal left anterior descending artery (LAD) with a minimum of patient discomfort.


A heart model for understanding three-deminsional cardiac anatomy.

A simple procedure for making cardiac casts has been described. These casts aid in the understainging of the special relationships of the ventricles, valves and coronary arteries as they appear at the time of cardiac angiography.


Recurrent catheter-induced coronary artery spasm.

Catheter-induced spasm has generally been considered to represent an iatrogenic phenomenon without important clinical significance. This report describes two patients who developed catheter-induced spasm in the proximal segment of the right coronary artery in separate studies performed in different laboratories by means of different catheter techniques. One of these patients developed right coronary spasm on three occasions and, in addition, developed catheter-induced spasm of the left main trunk during two different studies. These observations would add support to the hypothesis that a predisposition to coronary artery spasm may exist in certain individiuals. Catheter-induced spasm deserves attention, since it may provide a means of identifying spasm-prone individuals.


The genome of Uukuniemi virus consists of three unique RNA segments.

The three RNA species isolated from virions of Uukuniemi virus, a proposed member of the newly defined Bunyaviridae family, have been characterized by analysis of 32P-labeled ribonuclease T1 oligonucleotides separated on two-dimensional polyacrylamide gels. Each species contains unique oligonucleotides not present in the two others, indicating that the genome of this virus is segmented. Each segment appears to contain a unique primary sequence with little or no overlapping among the segments. The complexities of the RNA segments as calculated from the radioactivity in unique oligonucleotides of defined lengths are about 8000 (L RNA), 3500 (M) and 1900 (S) nucleotides. Since these values are similar to the molecular weights determined by other methods, each size class of RNA corresponds to a single molecular species. The presence of a 5' terminal pppAp ... structure in each RNA segment confirms indications from electron microscopy that the apparently circular RNA segments are not covalently closed. The absence of either a 5' terminal "cap" or 3' terminal poly(A) supports the concept that Uukuniemi virus is a negative strand virus.


Cowpea mosaic virus RNAs have neither m7GpppN ... nor mono-, di- or triphosphates at their 5' ends.

32P-labeled cowpea mosaic virus (CPMV) RNAs were analyzed for their 5' termini by three different fingerprinting standard procedures. These analyses showed unequivocally that CPMV RNAs lack a structure like m7GpppN ... at their 5' termini. In addition, neither mono-, di- or triphosphorylated [(p)(p)pN ....] termini were found in the respective fingerprints. The inability to label the 5' termini treatment with gamma-32P-ATP and polynucleotide kinase, either per se or after pretreatment with alkaline phosphatase, strongly suggests the absence of a free 5'-OH and a free 5'-phosphate at the 5' terminal nucleotide in CPMV RNAs. The various analyses also showed that no 2' -O-methylated nucleotides, N6-methyladenosines or pseudo-uridines are present in CPMV RNAs.


A methionine-reversible folate deficiency in rats following the acute administration of diethylnitrosamine and alpha-naphthylisothiocyanate.

Acute doses of the hepatotoxic agents diethylnitrosamine (DEN) and alpha-naphthylisothiocyanate (ANIT) to young adult male rats led to the production of a folate deficiency as determined by an elevated urinary excretion of formiminoglutamic acid (FIGLU) 2 to 4 days following administration of the compounds. High dietary levels of methionine significantly reduced the elevated levels of FIGLU produced by the 2 chemicals. Dietary folate had no significant effect on the excretion of urinary FIGLU. Although the hepatic levels of S-adenosylmethionine (SAM) were significantly increased in rats fed the high dietary levels of methionine, an acute dose of DEN did not depress the hepatic levels of SAM. The results indicate that the methyl-reversible folate deficiency caused by hepatotoxic agents is not the direct consequence of altered hepatic levels of SAM.


Effects of acute CS2 intoxication on protein metabolism in rat brain.

The effect of acute CS2 exposure on the rat brain protein metabolism was studied with control and phenobarbitone pretreated adult male rats 1, 4 and 46 h after exposure. Increased activity of acid proteinase was detected in both test groups 1 and 4 h after exposure and it was accompanied by changes in 14C-labelled leucine turnover as well as in RNA content. The changes were more conspicuous in cerebellum than in brain in both test groups while phenobarbitone pretreatment modified the brain response towards intoxication. This modification probably represents inherent effects of barbiturate on brain protein metabolism as well as altered metabolism of CS2. The activities of creatine kinase and nonspecific cholinesterase displayed only subtle changes as assayed in cerebral homogenate and serum. Thus a single acute CS2 intoxication apparently causes definitive transient changes in brain protein metabolism; serum enzyme determinations may not reflect the magnitude of these changes.


Photodynamic action of chlorpromazine on adenovirus 5:repairable damage and single strand breaks.

Chlorpromazine, a substituted phenothiazine, commonly used as a sedative, has been found to photosensitize the inactivation of human adenovirus 5 to wavelengths of light between 330 and 390 nm. The slope of the inactivation curve is three fold greater when fibroblasts from people having xeroderma pigmentosum (XP) were used as viral hosts than when normal fibroblasts were used, showing that at least two-thirds of the damage produced in the virions is repairable by normal human fibroblasts. The phototreatment of chlorpromazine sensitized virions also results in the production of DNA strand breaks, which correlate fairly well with the production of lethal viral damage as measured in XP fibroblasts. These findings suggest that the photosensitization of the skin observed in patients treated with chlorpromazine might be due to DNA damage.


Aryl hydrocarbon hydroxylase in mouse mammary gland: in vitro study using mammary cell lines.

The effects of 3-methylcholanthrene (MCA), 5,6-benzoflavone (betaNF), 7,8-benzoflavone (alphaNF) and pregnenolone 16alpha-carbonitrile (PCN) upon aryl hydrocarbon hydroxylase (AHH) were determined in primary mammary gland epithelial cell cultures prepared from the C3Hf-/Ki mouse. MCA elevated AHH activity by 3--4 fold after 24 h of treatment; alphaNF produced a 50% inhibition. The specific activity of AHH in these cells was elevated by 6 h after exposure to MCA; enzyme activity was still maximally elevated after 48 h. The effects of MCA were also investigated in a group of mammary cell lines, one of which was derived from a control virgin mouse, the MCG V14; 3 of which arose from mammary tumors, MCG T10, MCG T14 and MCG T19; and 2 of which were sublines developed from hyperplastic alveolar nodules, HAN-1 and HAN-2. Induction was seen in all lines at 24 h, with the MCG T14 being the most responsive and the HAN-2, the least. Although the MCG T19 tumor cells did respond in culture, when implanted in the mouse, the AHH of the subsequent tumor was not elevated upon administration of MCA in vivo.


Vulnerability of the mildly ischemic ventricle to cathodal, anodal, and bipolar stimulation.

We studied the difference between myocardial vulnerability to arrhythmias caused by cathodal, anodal, and bipolar stimulation in 29 dogs with partial right coronary artery occlusion. We used 2-msec duration stimuli of up to 8 mA to determine the ventricular vulnerable periods, their relationship to the refractory periods, and the fibrillation or multiple response thresholds for unipolar anodal and cathodal stimulation after two premature ventricular contractions. The vulnerable period for arrhythmias began at the end of the respective refractory periods and terminated at a specific time within the cardiac cycle. Within this period the arrhythmia and excitation thresholds were equal. Because shorter refractory periods were obtained with anodal stimulation than cathodal, the vulnerable periods for anodal stimulation were longer. This indicated that the vulnerable periods for bipolar stimulation also would be longer than for unipolar cathodal stimulation since bipolar and anodal refractory periods are equal when the cathode and anode are of similar surface area. Results from seven of the experiments showed that a dual focus of excitation, which can only occur with bipolar stimulation, did not make the ventricle more vulnerable to arrhythmias than did unifocal stimulation. These results indicate that the difference between the arrhythmia vulnerability to unipolar cathodal, anodal, and bipolar stimulation is dependent on the relationship between their excitability characteristics, i.e., their strength-interval curves.


Influence of prostaglandin E2, indomethacin, and reserpine on renal vascular responses to nerve stimulation, pressor and depressor hormones.

The effects of prostaglandin E2 (PGE2) indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE2, 0.03 and 0.3 microgram/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. Responses to nerve stimulation were decreased to a greater extent than responses to norepinephrine. At lower concentrations the effects of PGE2 on pressor responses and on vascular resistance could be separated. Reserpine decreased the histochemical evidence of adrenergic innervation and reduced the response to renal nerve stimulation, enhanced the response to norepinephrine, and was without effect on the response to angiotensin. Indomethacin decreased depressor responses to arachidonic acid, produced a small increase in renal vascular resistance but did not enhance renal pressor responses. The increase in renal vascular resistance after indomethacin was not modified by reserpine pretreatment. Indomethacin enhanced the renal response to bradykinin. These data show that PGE2 possesses the ability to modulate pressor responses in the kidney. However, experiments with indomethacin suggest that endogenous prostaglandins neither modulate pressor responses nor mediate the response of the renal vascular bed to bradykinin. In addition, these data suggest that the increase in renal resistance after indomethacin is not dependent on the adrenergic nervous system.


Expanding the scope of educational psychology.

This paper describes the way in which a psychologist has workded in day nurseries in an Inner London Borough. The work has involved the development of an assessment form to be used with the children, and the planning of support groups for the day nursery staff. A brief outline is given of the research design necessary to evaluate the effectiveness of this intervention. It is to be hoped that the study indicates one way in which educational psychologists may extend their range of activities into the preschool area, and maximize the use of their skills in the field of childhood disadvantage.


The rabbit as an animal model for the activated factor X-antithrombin III-heparin reaction.

When activated factor X (Xa) inhibitory activity of serially diluted human and rabbit plasma is determined in a low salt assay, a lineare plot is obtained for human, but not for rabbit plasma. When a high salt assay is used, the dilution curves for both human and rabbit plasma are linear, and qualititive as well as quantitative differences are essentially eliminated. On Sephadex G-200 chromatography Xa inhibitory activity of human and rabbit plasma appears in two peaks. With the low salt assay the first and second peaks for human plasma contain respectively 30%, and 70% of the activity; whereas with rabbit plasma these values are greater than 95% and less than 5% of the activity. With the high salt assay the figures for human plasma are less than 5% and greater than 95%, and with rabbit plasma 65 +/- 3% and 35 +/- 3%, respectively. With the high salt system, rabbit plasma shows a continuous increase in Xa inhibitory activity with increasing heparin concentrations, similar to that obtained with human plasma. In the high salt system the relative contributions of antithrombin III  to Xa neutralization in human and rabbit plasma are different. However, in experiments in which Xa inhibitory activity of antithrombin III is altered by heparin, a simple formula, Total activity (%) = 65% + 0.35 x human plasma (%), permits translation of rabbit data on the Xa-antithrombin III-heparin reaction to man. On the basis of these findings, the rabbit model can effectively be used to study the Xa-antithrombin III reaction.


Detection of myocardial infarction in vitro based on altered attenuation of ultrasound.

This study was designed to determine whether attenuation of ultrasound by myocardium is potentially useful in detecting and quantifying infarction. Accordingly, we analyzed 44 regions of myocardium from 11 dogs 4-10 weeks after coronary occlusion. Attenuation of ultrasound in each region was assessed by transmitting a broadband pulse through the tissue in vitro and carefully gating the appropriate pulse into a spectrum analyzer for Fourier analysis (frequency range, 2-9.5 MHZ). An ultrasonic index of attenuation was derived from the slope of the best-fit line relating attenuation and frequency obtained from the Fourier transform. Acquistion of ultrasonic data was improved with the use of a specially designed small diameter receiving transducer. Myocardial creatine kinase content was assayed in each region to provide an independent index of regional injury. Results obtained from ultrasonic and biochemical analyses correlated with a correlation coefficient between the two of 0.80 in 24 regions of myocardium from the six dogs studied 4-5 weeks after infarction, and 0.72 in 20 regions from the five dogs studied 9-11 weeks after infarction. These findings indicate that regional infarction is associated with quantitative changes in ultrasonic attenuation.


Trophic influence of the sympathetic nervous system on the rat portal vein.

Adrenergic denervation of the rat portal vein was produced in vivo by the sympatholytic agent 6-hydroxydopamine (6-OHDA). Treatment of rats with 6-OHDA decreased the responses of the portal veins to nerve stimulation, reduced 3H-norepinephrine (NE) uptake, and decreased catecholamine fluorescence, indicating that partial adrenergic denervation was achieved. The main findings of this study indicate that the in vivo denervation produced: (1) a (time-dependent) increase in sensitivity of the veins to NE, which was not of prejunctional origin, (2) an increase in sensitivity to BaC12, and (3) a partial depolarization of the myovascular cells. The results suggest that the in vivo denervation of the portal veins by 6-OHDA produces a postjunctional alteration, which may be due to the removal of a trophic influence of the sympathetic nervous system. It is proposed that the partial depolarization and associated ionic changes may be components of the mechanism. These results provide the first direct evidence that membrane excitability changes are involved in trophic nerve-muscle interactions in blood vessels.


Collateral circulation after renal artery occlusion in the rat.

We used angiographic and microsphere methods to evaluate the anatomic and functional features of renal collateral circulation in the rat. By the microsphere method, renal parenchymal blood flow was less than 1% of control 1 hour after occlusion of the main renal artery; 2.8% of control 1-2 weeks after arterial occlusion; and 1% of control 4-9 weeks after occlusion. Radiographic observations during chronic occlusion revealed numerous collateral vessels to the kidney. These vessels readily filled with angiographic contrast medium but the intrarenal circulation did not visualize. We conclude that collateral circulation to renal parenchyma is negligible after acute or chronic occlusion of the main renal artery in the rat. The rich anatomic plexus of collateral vessels has no functional significance and is unable to preserve viability of the parenchyma.


Intrarenal hemodynamics in cross-circulated hypervolemic and isovolemic rats.

The microsphere technique was used to measure renal blood flow and intrarenal flow distribution in cross-circulated pairs of rats. One rat of each pair was made hypervolemic by infusion of blood (2.3% of body weight), followed by intravenous reinfusion to urine to maintain intravascular expansion. The other rat of each pair, which also was urine-reinfused, was kept isvolemic throughout the experiment. As shown previously, blood infusion resulted in a large diuretic and natriuretic response in the hypervolemic partner, while a smaller but statistically significant response occurred in the isovolemic partner. Total renal blood flow did not change in the expanded rats and fell slightly but not significantly in the nonexpanded ones. Blood volume expansion was associated with a significant shift in microsphere concentration from outer to inner cortex. This shift was not, however, correlated with the magnitude of the renal response. The transferred natriuresis in isovolemic partners was not associated with any change in microsphere distribution. We conclude therefore, that redistribution of blood flow to the inner cortex, although a feature of intravascular expansion, is not the primary determinant of volume natriuresis. In addition, the natriuretic activity which develops in the blood of hypervolemic rats can reduce sodium reabsorption in isovolemic rats without intrarenal hemodynamic changes.


Electrical activity of sinoatrial node cells of the rabbit surviving a long exposure to cold Tyrode's solution.

The right atrium including the sinoatrial node was excised from the rabbit heart, immersed in Tyrode's solution, and kept at 0-3 degrees C for several days. The tissue then was warmed to 36-37 degrees C in well oxygenated Tyrode's solution. Transmembrane potentials from cells in the sinoatrial node region and the right atrium were recorded with microelectrodes. After 3 days of storage, the maximum diastolic potential of cells in the sinoatrial node region  decreased, but the configuration of the action potential was identical to that of the pacemaker pacemaker potential in the fresh preparation. After 5-7 days of storage, the sinoatrial node tissues in some preparations showed well preserved membrane potentials and pacemaker activity, while in others, the cells were electrically quiescent, or showed subthreshold oscillatory potentials of low amplitude. Transmembrane potentials could not be recorded from the right atrial tissue after storage for this period. Sinoatrial node action potentials with normal configuration were recorded from preparations stored for longer than 10 days. The sinoatrial cells in these preparations responded well to norepinephrine and acetylcholine, indicating that the reactivity of receptors was well preserved. The results provide electrophysiological evidence that cells in the sinoatrial node region can withstand long exposure to cold and retain their sensitivity to neuromediator action, but atrial myocardial cells cannot.


Aortic endothelial cell replication. I. Effects of age and hypertension in the rat.

The daily rate of cell replication in the aortic endothelium of the normal rat falls from a maximum of 13% at birth to 0.1-0.3% at age 5-6 months. This residual rate of replication largely represents the turnover rate of the endothelium in normal animals. After renal hypertension of 2-3 weeks duration, however, the rate of replication rises 10-fold to an average value of 1.6%. This increase may represent an increase in turnover; however, it probably represent, at least in part, a proliferative response to cover the expanded luminal surface of the dilated vessel.


The effect of norepinephrine on aortic 42K turnover during deoxycorticosterone acetate hypertension and antihypertensive therapy in the rat.

We studied the effects of norepinephrine on 42K turnover in aorta isolated from rats. The rats were given saline to drink and were made hypertensive by injections of deoxycorticosterone acetate (DOC). Other groups of rats received in addition either 6-hydroxydopamine (6-OH-DA) or a regimen of antihypertensives (Anti-Hy) consisting of reserpine, hydrochlorothiazide, and hydralazine. The weight, length, wall thickness, and circumference of the aorta also were measured. DOC hypertension was associated with increased 42K turnover (rate constant for DOC = 0.0164 +/- 0.0009 vs. 0.0090 +/- 0.0002 min-1 in controls). The responses of 42K turnover to low doses of norepinephrine (NE) were increased in DOC with an ED50 of 3.5 +/- 0.8 X 10(-9) vs. 2.7 +/- 0.5 X 10(-8) M in controls. The aortic weight, weight/length, and wall thickness were also increased. Rats treated with DOC plus 6-OH-DA had lower blood pressure and smaller changes in aortic dimensions; however 42K turnover and response to NE were similar to those of the DOC group. The Anti-Hv group exhibited only small increase in 42K turnover and aortic dimensions when compared to controls. It is concluded that DOC hypertension is associated with increased response of 42K turnover to NE which in turn may contribute to increased responses reported for contraction. The Anti-Hy regimen was more effective than 6-OH-DA in reducing the increased 42K turnover and response to NE associated with DOC hypertension.


The C19-mineralocorticoids in hypertension.

The excretion rates of the C19-mineralcorticoids, 16beta-hydroxy-DHEA and 16-oxo-androstenediol, were measured in subjects with low-renin essential hypertension and toxemia of pregnancy. C19-mineralocorticoid excretion in low-renin essential hypertension ranged from 70-790 microgram per day. No significant difference in 16beta-hydroxy-DHEA and 16-oxo-androstenediol excretion was found between these subjects and normal controls. Subjects with toxemia of pregnancy excreted between 350 and 2500 microgram per day of these steroids. There was no significant difference between toxemic and normal pregnancy. Thus, 16beta-hydroxy - DHEA and 16-oxo-androstenediol probably do not play an important role in either low-renin essential hypertension or toxemia of pregnancy.


A critical review of the systolic time intervals.

The theoretical basis for the use of the systolic time intervals has been largely established. The method has been validated by direct measures from within the circulatory system. Standards for equipment and technique have been defined. Numerous clinical studies have demonstrated the value of this quantitative noninvasive technique for assessing left ventricular performance. At present there is need for further studies of the clinical usefulness of the systolic time intervals to improve both diagnosis and therapy of various cardiovascular disorders.


The application of radionuclide infarct scintigraphy to diagnose perioperative myocardial infarction following revascularization.

To evaluate the application of radionuclide infarct scintigraphy to diagnose myocardial infarction after revascularization, we obtained postoperative technetium 99m pyrophosphate myocardial scintigrams, serial electrocardiograms and CPK-MB isoenzymes in ten control and 51 revascularized patients. All control patients had negative electrocardiograms and scintigrams, but eight had positive isoenzymes. Eight revascularized patients had positive electrocardiograms, images and enzymes and two had positive scintigrams and enzymes with negative electrocardiograms. Thirty-four patients with negative electorcardiograms and scintigrams had positive isoenzymes; in only seven patients were all tests negative. Our data suggest radionuclide infarct scintigraphy is a useful adjunct to the electrocardiogram in diagnosing perioperative infarction. The frequent presence of CPK-MB in postoperative patients without other evidence of infarction suggests that further studies are required to identify all factors responsible for its release.


Follow-up technetium-99m stannous pyrophosphate myocardial scintigrams after acute myocardial infarction.

Technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigrams were obtained in 68 patients during acute myocardial infarction (AMI) and at follow-up 15.9 +/- 8.8 weeks later. All patients with AMI had a positive scintigram (2+ or greater); only one of 46 control patients (2%) had a positive (2+) scintigram. At follow-up scintigraphy 6 to 37 weeks following AMI, 57% of patients had a persistently positive scintigram even though recurrent AMI was suspected in only one of these patients. Patients with persistently positive scintigrams tended to have more severe disease as evidenced by compensated congested heart failure (41%) persistent angina (77%), and ECG evidence of ventricular dyssynergy (51%), We conclude that 1) in patients with prior AMI, a 2+ abnormality on 99mTc-PYP scintigram may not represent new AMI; 2) a persistently positive 99mTc- PYP scintigram may have prognostic implications since it occurs predominantly in patients with severe symptomatic coronary disease.


The extraction of thallium-201 by the myocardium.

The concentration of thallium-201 in the myocardium immediately following injection of tracer is the result of both blood flow delivering tracer to the heart and extraction by the myocardium. In these studies, the extraction of thallium-201 by the canine myocardium was determined as a function of heart rate, coronary blood flow, hypoxia, changes in pH, and following administration of propranolol, insulin, and strophanthin. Under basal conditions, extraction fraction measured 88 +/- 2.1%, following pacing to a rate of 195 beats/min extraction fraction remained unchanged at 88.5%. Similar results were found with changes in pH, propranolol, insulin, and strophanthin. Hypoxia caused a significant decrease in extraction fraction to 77.9%. When coronary blood flow was increased in excess of demands by drugs, extraction fraction fell logarithmically.


Technetium-99m stannous pyrophosphate myocardial scintigraphy. Reliability and limitations in assessment of acute myocardial infarction.

Two hundred-three patients had -echnetium 99m (stannous) pyrophosphate myocardial scintigrams for the evaluation of chest pain and suspected acute myocardial infarction. In addition to routine imaging at 60--90 minutes after injection of the radio-pharmaceutical, the blood pool was imaged immediately in each patient for comparison with routine anterior, left anterior oblique, and left lateral views. Further delayed studies were obtained when residual blood pool activity was identified. Seventy patients had acute myocardial infarction by clinical, electrocardiographic, and enzymatic (CK-MB) criteria. Sixty-five of these 70 patients with acute infarction had positive myocardial scintigrams, with one technically unsatisfactory study. Only four of the 70 patients had negative scintigrams when imaged 18--72 hours after infarction in this study. Technically satisfactory scintigrams were recorded in 125 patients without evidence of infarction. Ninety-six had negative scintigrams at 60--90 minutes, while 19 patients (15%) had precordial activity at 60--90 minutes which was identical in distribution to early blood pool images and cleared with further delay. With these included, the true negative incidence was 92%. Ten of 125 patients had false positive scintigrams; two had recent cardioversion with resultant chest wall damage. The other eight patients had previous infarction 1 1/2 to 72 months earlier and had akinetic segments shown angiographically in the areas of the persistently positive scintigrams. Myocardial scintigraphy correlates well with the presence of other evidence of acute infarction, as well as with the absence of acute infarction when residual blood pool activity is identified. False positive scintigrams can occur following cardioversion and in patients with previous myocardial infarction and resultant ventricular wall motion abnormalities.


Correlation of angiographic estimates of myocardial infarct size and accumulated release of creatine kinase MB isoenzyme in man.

Accumulated creatine kinase MB isoenzyme release (sigma CK-MB) during acute myocardial infarction was correlated with biplane left ventricular (LV) angiographic estimates of percent abnormally contracting segment (%ACS) and ejection fraction (EF) in 35 patients who underwent diagnostic angiography at a mean of 33 +/- 4 days post myocardial infarction (MI). Of the 35 patients, 18 had no evidence of prior MI and their sigma CK-MB showed good correlation with %ACS (r = 0.84) and with EF (r = - 0.78). An additional two patients with first (inferior) infarct secondary to stenosis of the right coronary artery proximal to the origin of the right ventricular arterial blood supply had disproportionately large sigma CK-MB, suggesting a combination of LV and RV necrosis. In the 15 patients with prior infarct, there was no significant correlation between sigma CK-MB and %ACS or EF. However, in the subgroup of patients with anterior MI, %ACS correlated with sigma CK-MB, both in patients with no prior MI (r = 0.88, N = 12) and in patients with prior MI (r = 0.69, N = 9). These independent angiographic and enzymatic data suggest that enzymatic infarct size estimates utilizing accumulated CK-MB release may be a valid and reliable clinical measure for assessing the extent of LV necrosis in the setting of acute anterior myocardial infarction. However, limitations may exists in certain cases of inferior MI, probably because of concomitant right and left ventricle necrosis.


Continued incorporation of circulating radiolabeled fibrinogen into preformed coronary artery thrombi.

This study measured the growth over time of experimental coronary artery (CA) thrombi by radiolabeled fibrinogen uptake. 125I-fibrinogen was injected into dogs and 24 hours later CA thrombi were induced by electrical current. Twenty-four hours after CA thrombus induction, 131I-albumin (group A) or 131I-fibrinogen (group B) was injected. At 48 hours after thrombi induction, the thrombi were removed, divided into segments, and their radioactivity measured. The 131I-fibrinogen in the group B thrombi was significantly greater than the 131I-albumin in group A thrombi (P less than 0.001). In further studies, the 131I-fibrinogen was given 48 and 72 hours post CA thrombus formation. Significant 131I was also found in these CA thrombi. 125I-fibrinogen and 131I-fibrinogen incorporation occurred in virtually all segments of the thrombi. The results suggest 1) CA thrombi growth continues for at least 72 hours after initial formation; 2) the presence of 131I in the thrombi was due to gradual fibrin deposition throughout the thrombus.


The effect of acute coronary artery occlusion on subepicardial transmembrane potentials in the intact porcine heart.

Subepicardial transmembrane potentials were recorded from intact pig hearts to observe the changes induced by acute ischemia. Ischemia shortened action potential duration, and decreased its amplitude, upstroke velocity, and resting potential. The cells were unresponsive after 12 to 15 minutes of coronary artery occlusion, yet near normal action potentials could be restored by flushing the occluded artery with saline as late as 40 minutes after occlusion. The unipolar extracellular electrogram reflected unresponsiveness by a monophasic potential. Local refractory periods initially shortened by up to 100 msec. Later, postrepolarization refractoriness occurred and refractory periods lengthened often in excess of basic cycle length, thus resulting in 2:1 responses. The onset of early ventricular arrhythmias often coincided with a period of alternation and 2:1 responses, especially when these got out of phase in different regions. Reperfusion frequently led to ventricular fibrillation, and was associated with marked inhomogeneity in cellular responses. Re-entry within ischemic myocardium was the most likely mechanism for arrhythmias.


Re-entrant ventricular arrhythmias in the late myocardial infarction period. 3. Manifest and concealed extrasystolic grouping.

Re-entrant beats with regular extrasystolic grouping were seen in 44- of dogs 3--7 days following ligation of the anterior descending coronary artery. Utilizing direct recording of the re-entrant pathway (RP) from the epicardial surface of the infarction zone, we found extrasystolic grouping to be based on the infarction tachycardia-dependent conduction disorders in a potentially RP. Trigeminy and quadrigeminy were related, respectively, to a 3:2 and 4:3 Wenckebach-like conduction cycle in a RP. However, quadrigeminy could also be due to an underlying bigeminal rhythm with concealment of alternate re-entrant beats, i.e., concealed bigeminy. A bigeminal rhythm was the result of a 2:1 conduction pattern in a re-entrant pathway with a sufficient degree of conduction delay during the conducted beat of the 2:1 cycle to result in re-entry. A trigeminal or quadrigeminal rhythm could change to a bigeminal rhythm on critical shortening of the cardiac cycle. Fixed and variable coupling were related, respectively, to stable and changing conduction pattern in a re-entrant pathway. On the other hand, extrasystolic grouping could be concealed due to either block in the re-entrant pathway or entrapment in a small area of the closely bordering normal zone.


Electrocardiographic recognition of sinus node dysfunction in children and young adults.

Twenty-four children and young adults with electrocardiographic evidence of sinus node dysfunction (SND) are described. The patients, whose ages ranged from three days to 25 years, were divided into three groups based on the type of SND. Ten patients had persistent and inappropriate sinus bradycardia (group I): twelve patients had episodes of prolonged sinus arrest (group II); and seven patients had repeated episodes of Mobitz type I or II sinoatrial exit block (group III). Eighteeen patients had significant heart disease and in 11 of these the SND followed corrective cardiac surgery. Seven were operations for atrial septal defect and transposition repair. Seven patients with SND were symptomatic, having either syncopal (3) or near syncopal episodes (4). All three with syncope have received permanent demand pacemakers. These data show that sinotrial exit block occurs in many young patients with SND (29% in this series). Its recognition, however, requires careful electrocardiographic analysis in order to differentiate sinus bradycardia and sinus arrhythmia. Although SND most commonly occurs in children with congenital or acquired heart disease, particularly following corrective cardiac surgery, it may occur in the absence of other cardiac abnormalities.


Prognostic value of infranodal conduction time in patients with chronic bundle branch block.

His bundle recordings were obtained in 121 patients with chronic bundle branch block and the patients were followed for a mean period of 18 months. Seventy-nine patients had an infranodal conduction time (H-Q) less than 70 msec while 42 had H-Q greater than or equal to 70 msec. There was no significant difference in mean age, smoking history, diabetes, syncope, dizziness, blood pressure, and serum cholesterol or triglyceride levels between the two groups. There was a significantly greater incidence of progresssion to second degree or third degree atrioventricular block (9/42, 21%), and of severe congestive heart failure (16/42, 38%) in patients with H-Q greater than or equal to 70 compared with those with H-Q less than 70 (1/79, 1.3%; and 13/79, 16%, respectively). The risk of sudden death was significantly greater only in the group with H-Q greater than or equal to 70 and severe congestive heart failure. There was no correlation between the presence of first degree atrioventricular block and/or any particular type of bundle branch block pattern with sudden death and/or progression to second degree or third degree atrioventricular block. Analysis of the surface electrocardiogram is only of limited value in predicting high risk patients with chronic bundle branch block. Electrophysiologic studies are of greatest value in patients with bundle branch block with transient neurologic symptoms in whom no cause for the symptoms is evident.


Left precordial isopotential mapping during supine exercise.

Junctional depression is often observed during physical exercise in overtly normal subjects. To explore its pathogenesis, 15 normal volunteers were studied during supine, bicycle ergometer, submaximal stress tests. Electrocardiograms were simultaneously recorded from 42 electrodes on the left anterior precordium at two minute intervals at rest and during exercise. Data were used to construct isopotential maps throughout the P-QRS-T intervals. At rest, maps throughout the ST segment were dominated by a single maximum along the upper left sternal border. During exercise, all subjects developed junctional depression that was maximal along the lower left sternal border. Exercise maps during the early to mid-ST segment showed an intense minimum along the lower left sternal border that was continuous with terminal QRS forces in both intensity and location. Later in ST, this minimum decreased in strength and was replaced by a maximum located in the same area as that observed at rest. These observations suggest that junctional depression is the result of competition between two effects, one being normal repolarization which is obscured in the early ST segment by the second, possibly representing delayed terminal depolarization forces.


The determinants of atrioventricular nodal re-entrance with premature atrial stimulation in patients with dual A-V nodal pathways.

In patients with dual atrioventricular (A-V) nodal pathways, atrial extrastimulus testing induces either no echoes, single atrial echoes (Ae), or repetitive re-entrance (repetitive atrial and ventricular beating). We examined the fast and slow pathways properties in 38 patients with dual pathways in order to delineate the determinants of re-entrance. Seventeen patients had no Ae. Of these, six had no V-A conduction and 11, intact V-A conduction. The mean paced ventricular cycle length producing retrograde V-A block (VABCL) in this group (a measure of retrograde fast pathway refractoriness) was 552 +/- 32 msec (mean +/- SEM; 10 pts). In contrast, all 21 patients with Ae had intact V-A conduction with mean VABCL of 382 +/- 21 msec (14 pts) (P less than 0.05). Repetitive re-entrance occurred only when Ae conducted to the ventricles. Seven patients had only single Ae. The mean paced atrial cycle length producing Wenckebach periodicity (CLAWP) in this group (a measure of antegrade slow pathway refractoriness) was 490 +/- 31 msec (5 pts). Fourteen patients had repetitive re-entrance. The mean CLAWP in this group was 399 +/- 18 msec (8 pts) (P less than 0.05). In conclusion, our results suggest that in patients with dual pathway, the occurrence of single or repetitive re-entry is dependent upon measurable slow and fast pathway properties.


Digitalis in the pre-excitation syndrome. Analysis during atrial fibrillation.

The effect of digitalis in 21 patients with Wolff-Parkinson-White syndrome was anlayzed with respect to the ventricular response during atrial fibrillation and antegrade and retrograde refractory periods of accessory pathways. Digitalis shortened the cycle length of the most rapid ventricular response (shortest R-R) (i.e., increased the ventricle response) in 6/21 patients, increased the cycle length in 7/21 patients, had no effect on the cycle length in 5/21, and could not be determined in 3/21. Digitalis could be directly related to the onset of ventricle fibrillation resulting from atrial fibrillation in 9/21 patients. Each of these patients had shortest R-R intervals (220 msec or less) during atrial fibrillation in the control data. The results of this study indicate that no a priori prediction about the effect of digitalis on the antegrade conduction of accessory pathways can be made. By elective induction of atrial fibrillation it is possible to separate WPW patients into groups at high and low risk for developing ventricular fibrillation with the administration of digitalis.


Cross-sectional echocardiography in the diagnosis of congenital heart disease. Identification of the relation of the ventricles and great arteries.

Using a mechanical sector-scanner, two-dimensional echocardiograms were obtained from 28 normal subjects, 15 patients with tetralogy of Fallot, 11 patients with complete transposition of the great arteries and six patients with double outlet right ventricle. The image obtained perpendicular to the long axis of the left ventricle at the base of the venticular septum was superimposed on the image obtained perpendicular to the long axis at the origin of the great arteries. In normal subjects, these superimposed images demonstrated that the aorta originated posterior and to the left of the ventricular septum. In patients with tetralogy of Fallot, the aorta was displaced anterior and to the right resulting in the aorta over-riding the ventricular septum. In patients with double outlet right ventricle both great arteries originated anterior to the ventricular septum (i.e., from the right ventricle). In patients with complete transposition, the aorta originated anterior and the pulmonary artery posterior to the ventricular septum. Thus, cross-sectional echocardiography permits noninvasive identification of the relation of the ventricles and great arteries and, therefore, provides important information for the diagnosis of patients with congenital heart disease.


Echocardiographic assessment of a normal adult aging population.

Echocardiograms were performed on 105 male participants in the National Institutes on Aging's volunteer Longitudinal Study Program. All subjects (25--84 years of age) were physically active and had no evidence of hypertension or cardiovascular disease. Measurements were made of the initial diastolic (E-F) slope of the anterior mitral valve leaflet, the aortic and left ventricular cavity dimensions, and the thickness of the posterior left ventricular wall. Fractional shortening of the minor semi-axis of the left ventricle and the velocity of circumferential fiber shortening were also determined. It was found that increasing age correlated with a decrease mitral valve E-F slope and increased aortic root diameter and left ventricular wall thickness. Aging did not affect left ventricular cavity dimension, fractional shortening of the minor semi-axis, and velocity of circumferential fiber shortening. These findings suggest that aging in the normal male is associated with altered left ventricular diastolic filling, increased aortic root diameter and left ventricle hypertrophy but little change in contractile ability in the resting state.


Echocardiographic measurement of right ventricular wall thickness. A new application of subxiphoid echocardiography.

The feasibility of subxiphoid echocardiography to measure the thickness of the right ventricular wall (RVWT) was investigated. In 87 (90.6%) of the 96 patients studied, adequate visualization of the echoes from the right ventricular wall was obtained using the subxiphoid technique. RVWT averaged 0.34 +/- 0.08 cm (mean +/- 1 SD), ranging from 0.2 to 0.5 cm in 25 normal individuals. This was not significantly different from the values in the left ventricular overload group (0.36 +/- 0.10 cm). However, the RVWT was increased significantly (P less than 0.001) in the combined group (0.62 0.18 cm), the right ventricular (RV) pressure overload group (0.60 +/- 0.13 cm) and the RV volume overload group (0.53 +/- 0.11 cm). Thirty-two patients underwent diagnosis right heart catheterization which revealed a good correlation between the RVWT measured echocardiographically and the right ventricular peak systolic pressure (r = 0.84). Subxiphoid echocardiography was considered to be useful in diagnosing right ventricular hypertrophy in adults.


The effect of propranolol on canine myocardial CPK distribution space and rate of disappearance.

Canine myocardial CPK was partially purified and injected into 11 conscious mongreal dogs. From serial serum CPK measurements in each dog, mean Kd was calculated as 0.0047 +/- 0.0009 (+/- SD) min-1. Correlation coefficients indicated that CPK disappearance rate was well described by a single exponential expression. Kd measured on consecutive days in four dogs varied minimally. CPK distribution space ranged from 74 to 134% of plasma volume. Propranolol loading with 0.3 mg/kg or 2 mg/kg, followed by hourly maintenance doses, resulted in increased Kd in eight of ten dogs, mean Kd rising from .0048 min-1 to .0059 min-1 (P less than 0.02). Propranolol appeared to increase plasma volume but had no significant effect on the relationship of CPK distribution space to plasma volume. If the serial CPK technique were used to measure infarct size, using an average Kd, propranolol might produce artifactual reduction of infarct size measuremnt by increasing Kd and possibly by increasing plasma volume. The obligation to assess the effect upon CPK Kd and distribution space of an agent designed to limit infarct size is apparent.


Effect on training on myocardial oxygen supply/demand balance.

In five well-trained and five sedentary control subjects potential subendocardial blood supply was estimated from the diastolic pressure time index (DPTI) and myocardial oxygen demands from the tension time index (TII) during a progressive near-maximal treadmill test. DPTI/TTi was used to assess the effects of training on myocardial oxygen supply/demand balance. DPTI/TTI was significantly higher in trained subjects at rest and comparable workloads. At 6.4 km/hr, 18% grade (maximum for the controls), TTI was significantly lower (4300 +/- 76 vs 4495 +/- 99 mm Hg-sec/min) and DPTI significantly higher (2534 +/- 86 vs 2295 +/- 91 mm Hg-sec/min) in the trained subjects; DPTI/TTI was significantly higher (0.59 +/- .02 vs 0.50 vs .03). At near-maximal heart rates both groups achieved the same supply/demand balance (0.50); however, the trained subjects were working at higher workloads. We conclude that endurance conditioning increases work capacity, reduces myocardial O2 demands, increases potential O2 supply and improves the supply/demand balance at any given submaximal workload which reduces the risk of ischemia.


Chronic congestive heart failure after repair of tetralogy of Fallot.

The etiology of chronic congestive heart failure (CHF) after repair of tetralogy of Fallot was determined in 102 patients consecutively catheterized 1 to 12 years postoperatively. Chronic CHF was observed in 36/102 patients. The most prevalent abnormality leading to congestive failure (31/36) was a large residual ventricular septal defect alone or in combination with other lesions. All postoperative patients with pulmonary to systemic flow ratios greater than 2:1 (25/102) had congestive failure and evidence of biventricular dysfunction. Significant tricuspid regurgitation (N = 11) and persistent systemic to pulmonary artery shunts (N = 6) contributed to volume overload and congestive failure in the patients with large residual ventricular septal defect. Isolated severe residual right ventricular outflow tract obstruction was a common cause of chronic CHF. Pulmonary artery hypertension was present in 20/36 patients with CHF. The increased pulmonary pressure was not wholly due to an increased pulmonary flow since 7/20 patients had pulmonary vascular resistance greater than 3 mm Hg/L/min/m2. Our findings indicate that persistent or chronic congestive heart failure in postoperative tetralogy of Fallot patients requires bilateral cardiac catherterization since an identifiable and surgically correctable lesion is nearly always present.


Abnormal left ventricular contraction pattern in the systolic click-late systolic murmur syndrome.

A contraction abnormality of the left ventricle has previously been described in patients with systolic click-late systolic murmur syndrome. To determine if the contraction abnormality is present in the preprolapse period, LV dimensions and the instantaneous velocity of circumferential fiber shortening (VCF) were studied in 18 patients with the mitral valve prolapse and 16 normal subjects using computer analysis of echocardiograms. VCF attained its maximum (max VCF) during the preprolapse period an average of 94 msec before the mid-systolic click. Max VCF was significantly reduced in patients with mitral valve prolapse (2.06 vs 2.55 circ/sec in normal subjects, P less than 0.001). Despite the reduction in max VCF, no difference in the extent and percentage of diameter shortening was found between patients and normal subjects. This discrepancy is explained by a sustained rate of mid-to-late systolic diameter shortening in the presence of mitral valve prolapse as manifested by a typical VCF profile (P less than 0.001) and a longer duration of diameter shortening (353 vs 306 msec in normal subjects, P less than 0.01). The decrease of max VCF in patients with mitral valve prolapse suggests a reduction in LV contractility. Since the abnormality is present in the preprolapse period, it is unrelated to a direct mechanical effect of the prolapse itself. Additional fiber shortening in mid-to-late systole indicates that the sudden displacement of the mitral leaflets may have an unloading effect on the left ventricle.


Effect of increased free fatty acids on myocardial oxygen extraction and angina threshold during atrial pacing.

To evaluate whether elevated arterial free fatty acids (FFA) increase myocardial oxygen demand and ischemia, 15 fasting patients with coronary artery disease underwent a standardized atrial pacing test before (PTI) and during (PT2) heparin infusion. The patients were monitored for clinical and electrocardiographic (ECG) manifestations of ischemia. Myocardial extraction of lactate, inorganic phosphate, oxygen and FFA was measured before and during each PT. The control arterial FFA was 0.65 +/- 0.03 micromole/ml and rose to 1.83 +/- 0.16 micromole/ml during heparin influsion. Myocardial oxygen extraction at rest and during PT was not affected by the increase in arterial FFA. Seven patients asymptomatic during PT1 did not develop ischaemic manifestations during PT2. In eight patients with angina during both PTs, increased arterial FFA concentration did not modify the severity of anginal pain, the amount of ST-segment depression and the myocardial balance of lactate or inorganic phosphate. Elevation of arterial FFA by heparin neither increased myocardial oxygen extraction at rest or during pacing nor accentuated ischemic manifestations during PT.


Clinicopathologic correlations. De subitaneis mortibus. XXV. Sarcoid heart disease.

Postmortem findings within the cardiac conduction system are described from the case of a black woman with sarcoid heart disease who died suddenly. Her clinical course had been characterized by recurring ventricular arrhythmias and bouts of syncope. Both the sinus node artery and the atrioventricular (A-V) node artery were sites of focal fibromuscular dysplasia, which thickened slightly the wall of the former but markedly narrowed the lumen of the latter. Small foci of sarcoid infiltration were present in the sinus node and the A-V node. Fatty replacement within the His bundle was attributable to the probable ischemia caused by narrowing of the A-V node artery. Sarcoid granulomata and infiltration with epithelioid cells were present throughout the ventricular myocardium, but were conspicuously less prevalent in the atria. All the large coronary arteries were normal. Many small coronary arteries in the ventricular myocardium were involved by the sarcoidosis and their lumen were narrowed. These findings and analogous ones reported by others are discussed relative to the pathogenesis of syncopal attacks and sudden death which seem to peculiarly prevalent in sarcoid heart disease.