The measurement of expressed emotion in the families of psychiatric patients. In a series of studies of the influence of family life on the course of an established schizophrenic illness, it has been shown that the level of emotion expressed by relatives shortly after a schizophrenic patient is admitted to hospital is strongly associated with symptomatic relapse during the nine months following discharge (Brown et al., 1962, 1972). This paper states the case for an abbreviated version of the primary research instrument used in these studies, the Camberwell Family Interview Schedule. In the 1972 study the single most important measure contributing to the overall expressed emotion index proved to be the number of critical remarks made about the patient by the relative when interviewed alone. An analysis of 15 tape-recorded interviews from this study showed that the majority of critical comments were produced within the first hour and there was virtually no relationship between total number of critical comments and length of interview (r = 0.08). This analysis supported the use of a shortened interview in which the areas most likely to produce any criticism were given priority in the sequence of questioning. This abbreviated version has been used successfully in a replication and extension of the 1972 study. A group of 37 schizophrenic patients is being compared with a group of 31 depressed neurotic patients. Patterns of emotional response of these patients' relatives are discussed.


A further attempt to cross-validate the grid test of schizophrenic thought disorder. A retrospective investigation to assess the validity of the Grid Test of Schizophrenic Thought Disorder (Bannister & Fransella, 1966, 1967) is reported. Analysis of the data revealed that, while there is some evidence to support the validity of the test, it failed to discriminate between clinically assessed thought-disordered and non-thought-disordered patients at an acceptable level of significance, and that the rate of misclassification was too high to justify the use of the test in the assessment of an individual case. The results are compared with the findings of other published studies, and weaknesses in methodology, due to the retrospective nature of the study, are also discussed.


Attention and information processing in schizophrenia. The performance of 20 acute schizophrenics and 10 depressives, matched for age, verbal intelligence, and pre-morbid functioning, was assessed on a choice reaction-time card-sorting task. Stimulus and response uncertainty were varied independently, and there were two main conditions, distraction and no distraction. The schizophrenics were slower than the depressives over all the functions examined in the study. Schizophrenics were significantly more affected by increases in response uncertainty than the depressives. Although there was a tendency for the schizophrenic group to be more affected by distraction and by increasing stimulus uncertainty, these differences were not significant. There was no significant interaction between the effects of stimulus and response uncertainty, nor between the effects of distraction and stimulus uncertainty. The effects of distraction increased with increasing response uncertainty. The results are discussed in relation to two models of information processing, suggested by Broadbent (1971) and by Sternberg (1969). Such models allow a more detailed examination of the cognitive abnormalities found in schizophrenia.


Bone disease in long-term haemodialysis: the association of radiological with histological abnormalities. The radiological findings in the skeletal surveys of 70 patients receiving long-term haemodialysis for chronic renal failure have been correlated with histological findings in a specimen obtained by biopsy of the iliac crest. Many significant associations were found, and the ones presented are those thought to be most useful in the interpretation of the radiological abnormalities. The main conclusions are that fractures and severe medullary rarefaction appear to be most commonly the result of osteomalacia; subperiosteal erosions are associated with the more severe grades of osteitis fibrosa; cortical striations and sclerosis are associated with an increased amount of osteoid, and sclerosis is diagnosed more frequently by radiological means than by iliac-crest biopsy.


Loss of renal tissue in the elderly.

Loss of renal tissue in the elderly. Eighty-eight kidneys obtained at necropsy from normotensive subjects aged over 50 years were examined histologically and by post-mortem pyelography and angiography. Moderate or severe scarring was present in 50%. Its distribution and the absence of calyceal deformity make pyelonephritic scarrig unlikely. Its extent was related to the severity of change in the renal vessels, but not to age. On pyelograms, scarring was difficult to distinguish from fetal lobation. Kidneys with the most severe histological changes in the vessels tended to show the most marked angiographic distortion, though in general the two techniques examine different parts of the renal vascular bed. Total renal area and "cortical" area, measured from the angiograms, were not significantly correlated with age, thouth both tended to be smaller in older subjects. These dimensions, particularly cortical area, were significantly correlated with vascular changes, being smallest when vessels were most markedly affected. Results suggest that the loss of renal tissue which occurs in the elderly, particularly selective loss of cortex, is more closely related to events in the renal vasculature than to age itself.


Septal lines in pure right heart failure. Two adult patients are described with pure right heart failure and chronically elevated systemic venous pressure. Neither patient had evidence of pulmonary venous hypertension, but both had septal lines. This unusual finding may be the result of impaired centripetal lymph flow in the lungs due to obstruction of the drainage of the thoracic duct by raised systemic venous pressure.


The absorbed dose to bone marrow in the treatment of polycythaemia by 32P. This paper reports the determination of absorbed dose to bone marrow in the treatment of polycythaemia by 32P, based on the measurement of activities in bone and marrow biopsies taken at various times from 1 to 27 days after injection of the radionuclide. Activities were measured in the cortex, trabeculation and marrow of biopsies taken from the iliac crest, and slso in sternal marrow. The biological  half-life of 32P in marrow from the iliac crest was found to be  nine days; that derived for sternal marrow was lower, but the difference was not statistically significant; the value for trabecular bone was 27 days. The biological half life for 32P in the body, as measured by whole-body counting, was 39 days. Calculations of the dose-rate to trabecular marrow have been made by a method based on that of Whitwell and Spiers (1971), but modified to allow for the presence of32P in the marrow as well as in trabecular bone. The dose-rates follow a single exponetial decay with a half-life of 6.7 days. The intergrated dose including that during the first day is 24 rad per mCi injected.


Bowel gas--a cause of elevated dose in radiotherapy. The presence of gas in bowel could lead to higher than expected doses being given in the radiotherapy of abdominal and pelvic tumors. Radiation detectors were placed in the uterus and vagina of ten patients with caricnoma of cervix, and the actual dose compared with that expected when anterior fields of treatment were employed. Elvations greater than 10% were obtained in six, and severe postradiation morbidity subsequently occured in two of the three showing the highest readings.


Prediction of human spleen size by computer analysis of splenic scintigrams. A method of assessing spleen size from splenic scintigraphs obtained using autologous heat damaged 99Tcm labelled red cells is described. The method depends on a "computed volume" estimate. The method has a correlation coefficient of 989 with the exsanguinated weight ofthe spleen after splenectomy and has been shown to have an accuracysuperior to methods previously described.


Gallium-67 imaging to localize urinary-tract infections. To differeniate upper from lower-tract urinary infections, 73 patients were imaged with 67Ga citrate. Renal uptake of the radioisotope occurred in pyelonephritis (documented in 47 patients by ureteral cathieterization, bladder washout, or  histology) with an accuracy of 86%. There were 15% false-positives and 13% false-negatives. 67Ga may prove to be a clinically valuable test in the diagnosis of pyelonephritis. Results are promptly available 24 hours after injection, and it is non-invasive test that can safely be repeated to follow recurrent infections.


Some in vivo effects of pi mesons in mice. The effect of 70 MeV pi mesons was studied to determine the effectivness of such beams aginst normal tissues in vivo. The end points included thymic weight loss, oocyte and bone marrow CFU-S survival and the induction of macroscopid lens opacities. The results indicate that pi mesons are not signifacantly more effective for these end-points than more conventional radiation sources such as 60Co gama rays, 220 kVp X rays, and 14 MeV X rays and electrons. Nor was there any detectable difference in RBE between the peak and plateau regions of the pi meson beam. The significance of these findings is discussed in relation of the the published pi meson RBE values of between 1 therefore 4 and 5 therefore 0.


Response of HeLa cells to irradiation with pi- mesons. HeLa cell suspensions were irradiated at various depths of Perspex in a beam of 70 MeV pi- mesons. The dose-rate in the Bragg peak varied between 40 rad hour-1 and 150 rad hour-1. The cells were assayed in vitro for loss of reproductive integrity. The results for irradiation in the peak indicated an RBE of about 2-1 when compared to the response obtained using 60Co gamma-rays at comparable dose-rates. At dose-rates of 100-150 rad hour-1, the RBE peak-to-plateau was about 1-4, while at lower dose-rates, the RBE peak-to-plateau was about 1.


A radiological study of morphology and growth in the human fetal colon. A radiological study has been made of the colon in 64 human fetuses between 11 and 20 weeks gestation (64-160 mm crown rump (CR) length). A dynamic picture of colon development was obtained from analysis of the radiographs. The findings challenge textbook descriptions, but can be interpreted in terms of the ultimate morphology of the colon. According to the morphology of the proximal (pre-splenic) part of the colon, there are three types of colon. In Type 1 it lies transversely, in Type 2 it is oblique in direction, and Type 3 has a postnatal form with ascending and transverse elements. Although the Type 1 predominates in smaller fetuses and the type 3 is most common in larger fetuses, there is some overlap in their distribution. The ileocaecal junction does not descend, but actually slightly ascends as the fetus grows. The splenic flexure grows in a distinctly cranial direction, and at almost three times the rate of the ileocaecal junction. Thus, as the fetus develops, the ileocaecal junction and splenic flexure grow further apart, and this determines the change from a Type 1 to a Type 2 colon. The divergence of the ileocaecal junction and splenic flexure appears to be related to different rates of growth in the colon, the distal (post-splenic) part growing almost half as fast again as the proximal (pre-splenic) part. The more mature (Type 3) form of colon appears to result from conversion of the Type 2 following early adhesion between the proximal colon and the second part of the duodenum.


Nephrographic density and renal diatrizoate content in experimental acute renal failure. Reversible acute renal failure (ARF) was induced in rats by intramuscular injection of glycerol. In these animals and controls, renal concentrations of 125I-labelled sodium diatrizoate, injected intravenously in doses similar to those used clinically, were compared with the density of the nephrogram, subjectively assessed under carefully controlled conditions. Though a good statistical correlation existed between renal diatrizoate concentration and nephrographic density, individual variation was wide. At any given level of renal iodine concentration, nephrograms were judged to be denser in ARF than in controls. This was not due to differences in whole-body opacification or renal size, but was partly explained by the greater visibility of renal outlines on plain films in ARF. However, though at all doses of diatrizoate renal iodine concentrations were higher in controls, differences in nephrographic density were in general difficult to detect.


The diagnostic value of sialography and scintigraphy in salivary gland diseases. The diagnostic value of sialographic and scintigraphic investigations was compared in 169 patients. In this group were 75 inflammatory diseases and 49 benign and malignant tumours. Sialograms and scintigrams were examined by different physicians who had no knowledge of the clinical data of the patients. The scintigraphic diagnosis was considered correct if any abnormal finding was noted. The sialographic diagnosis was considered correct if the actual disease was diagnosed. In spite of the less stringent requirements for a correct scintigraphic diagnosis the sialographic technique was found to be superior. Radioactivity uptake curves over the salivary glands did not improve the scintigraphic diagnostic accuracy.


Regional blood flow in human tumours with special reference to the effect of radiotherapy. Blood flow in 41 superficial tumour nodules, of which nine were lymphomas, nine anaplastic carcinomas and 23 differentiated malignomas was measured using the 133Xe-clearance method. The lymphomas showed statistically higher blood flow (38-4 ml./min/100 g) than anaplastic (11-4 ml./min/100 g) and differentiated tumours (13-7 ml./min/100 g). After one week of radiation treatment the mean blood flow in anaplastic carcinomas was higher than the initial value. After an interval following the end of the radiation treatment the circulation diminished significantly compared with that observed immediately at the end of radiotherapy. The size of the tumours did not correlate with the blood flow.


Method of constructing a dose-response curve for normal cells in situ. A method is presented for planning experiments and analysing data with a view to determining in detail the shape of a single-dose survival curve for normal cells exposed in situ to relatively low doses of radiation. Applying this method to data published on the responses of gastric mucosal and colonic stem cells showed that the single-dose survival curves for these cells were linear up to about 250 rads, after which they bent downwards. Some applications of this method are discussed.


Recovery in mammalian cells irradiated with a beam of pi--mesons. HeLa cells have been irradiated in a beam of pi--mesons using fractionated exposures. The response-time curve for cells irradiated in the peak and in the plateau regions showed evidence of recovery. For cells irradiated in the post-peak position recovery was either absent or delayed.


A comparison for use in radiotherapy of neutron beams generated with 16 and 42 MeV deuterons on beryllium. The physical and radiobiological properties of two neutron beams have been compared. The beams were generated by deuterons of 16 MeV at Hammersmith Hospital and 42 MeV at Harwell, in both cases falling on a Be/Cu target. The dose-rate and depth-dose characteristics at the higher energy were found to be superior to those at the lower energy. Collimation and shielding at the higher energy are facilitated by the greater degree of forward-peaking and by the fact that a higher dose-rate allows longer collimators to be used. Attenuation in iron was found to be similar at the two energies. The radiobiological properties of the two neutron beams are very similar. There is a difference of about 20 per cent in RBE for effects on mammalian tissues for doses between 300 and 2,000 rad of neutrons. The OER and the sparing effect of two large fractions are the same for the two beams.


Some observations on the medulla of the kidney. Terminology of the cortex of the kidney is discussed and some new terms are suggested. Observations are described on 50 kidneys which have been injected and variously dissected. These include descriptions of the medulla, papillae and calyces. Some developmental, radiological and surgical aspects are mentioned and suggestions for further study are made.


Crossed renal ectopia with colic. A clinical clue to embryogenesis. A clinicopathologic correlation of 2 patients with crossed renal ectopia presenting with ureteric colic and 4 cases collected from the literature is presented. The correlation serves to reaffirm the theory of ureteral and not renal, migration as the primary aberration resulting in this defect.


Hydronephrosis and polycythaemia.

Hydronephrosis and polycythaemia. 2 cases of secondary polycythaemia apparently caused by hydronephrosis are described. The polycythaemia resolved following nephrectomy in each case.


A simple method for studying the formation of calcium oxalate. The nucleation and crystal growth of calcium oxalate were studied under different conditions using a nephelometer to measure the turbidities of suspensions produced when dilute solutions of calcium chloride dihydrate and sodium oxalate were mixed. The amount of material produced was less when calcium was in excess of oxalate than vice versa. For equimolar amounts of the precipitating reagents the rate of formation of calcium oxalate was rapid when calcium and oxalate concentrations were 1-25 mmol/l. but slow when they were 0-5mmol/l. Sodium citrate and heparin inhibited nucleation and crystal growth and at certain concentrations prevented nucleation for the duration of the experiment. The method is simple and quick and requires only a small amount of material.


Abnormalities of detrusor and sphincter function in multiple sclerosis. Bladder and urethral function was studied in 52 patients with multiple sclerosis using gas-cystometry combined with sphincter electromyography. 96% of the patients showed abnormalities of either detrusor or sphincter function. The abnormal patterns discovered indicated demyelinating lesions in the corticospinal as well as in the reticulospinal tract. Urgency and urge-incontinence were the predominant symptoms, whereas no signs of involvement of the upper urinary tract found. The use of gas-cystometry provides a fast and differentiated method for assessment of the detrusor function.


A case of Behçet's disease involving the bladder. A case of Behçet's disease involving the bladder has been described. It resembled a bladder carcinoma. The pathology, aetiology and treatment have been briefly outlined.


Cryosurgery for prostatic obstruction using liquid nitrous oxide. The history of the use of liquid N2O for prostatic cryosurgery is briefly reviewed and an account given of a new simple instrument. Details are given of the first 3 operations and of the results of another 82 performed at a number of different centres. Relief of acute or chronic obstruction was obtained in about two-thirds of the patients, all of whom were elderly and unfit for conventional operations. There were no serious complications attributable to the operation and it was suggested that it would be justifiable to offer it as an alternative, to patients who are fit for conventional surgery.


Latent carcinoma of the prostate: the probability of identifying small lesions in routine histology. In 3,072 open prostatectomy specimens covering a 25-year period 117 (4%) showed frank carcinoma. A further 74 cases showed areas of occult carcinoma or atypical hyperplasia. These focal lesions had an average diameter of 1 mm and 96% were situated in the peripheral regions of the specimen. In view of the situation of these lesions and their small size, an improved method of taking blocks for histological sections from prostatectomy specimens is proposed, resulting in an increased probability of demonstrating the areas of occult malignancy.


Introital bacterial flora - effect of increased frequency of micturition. Introital swabbing was performed on each of 20 premenopausal female volunteers over a 5-day period, 2 swabs being collected each day. During the last 3 days of the 5-day period the volunteers were requested to void every 2 hours. Analysis of our data shows: 1. Perineal bacterial flora varies in number and type of organisms from hour to hour and day to day. 2. Quantitative culturing is of little help in distinguishing colonisation of the introitus with urinary pathogens from mere intermittent contamination of the introitus with the same pathogens. 3. Our results suggest that 4 or more consecutive isolates of the potential urinary pathogens from the introitus over a 48-hour period signify colonisation. 4. Frequency of micturition increases the risk of colonisation of the introitus with potential urinary pathogens. The significance of these findings is discussed, in relation to the previous work of other investigators.


Adrenal aldosterone-producing adenoma: use of colonic potential in diagnosis and subtraction scanning technique for localisation. Primary hyperaldosteronism is a potentially curable cause of hypertension, and much interest has been shown in methods of diagnosing the associated hypokalaemic hypertension and localising the adrenal adenoma. In two patients the diagnosis of primary aldosteronism was confirmed by colonic potential measurement and the adenoma localised by a new subtraction technique for early adrenal imaging applied to the use of 131I-19-iodocholesterol. Both patients underwent adrenalectomy and in each case an adenoma was removed. Blood pressure and electrolyte levels returned to normal after operation. In one patient bilateral adrenal phlebography had failed to show the tumour, and sampling of aldosterone concentrations in the adrenal veins had been unsatisfactory.


Doppler ultrasound method for detecting human fetal breathing in utero. An audible Doppler ultrasound method for detecting human fetal breathing movements in utero has been developed. The frequencies synchronous with fetal breathing movements probably originate from the lung rather than the chest wall. This method is much cheaper and simpler than the ultrasound A-scan method and is suitable for screening large numbers of people.


Ten-year follow-up report on Birmingham Diabetes Survey of 1961. Report by the Birmingham Diabetes Survey Working Party. In a diabetes survey in 1960-1, 808 patients from a whole-practice population who either had glycosuria or were used as age- and sex-matched controls were given a 50-g oral glucose tolerance test (GTT). Ten years later the test was repeated in 382 cases. Of the original group, 126 had died and a similar number refused the second test. The original GTT results were classed as normal or as showing GTT diabetes, lag storage, renal glycosuria, or miscellaneous abnormalities. Most of those who converted to florid diabetes came from the GTT diabetes group, all the remainder having shown another minor degree of abnormality in the test; 23% with GTT diabetes, however, remained unchanged, while 32% returned to normal or had only minor anomalies. Of the original lag-storage group 57% remained unchanged or became normal, though 24% had converted to a diabetic abnormality. Renal glycosuria was an innocent peculiarity. The various miscellaneous abnormalities tended to change and showed an excessive conversion to diabetes. There was no accelerating trend towards diabetes in the second five years of follow-up. Those who developed florid diabetes showed an excess mortality comparable to that of clinical diabetics in general. Those who remained normal had the lowest mortality, while those with minor abnormalities occupied an intermediate position.


Differentiation of Bergmann glia cells in the cerebellum: a golgi study. The migration of Bergmann glia cells from the external granular layer to the Purkinje cell layer and the differentiation of their processes were analyzed in Golgi-Cox preparations of the cerebellum of the rat. During their migration they showed numerous cytoplasmic excrescences and long thick processes, which suggested that they may follow ameboid form of movement for their migration. The differentiation of their processes was observed to involve a series of complex events related to retraction of the thick apical processes from the tips of which sheaves of filiform processes emerged, growth in the number and the thickness of the filiform processes, resorption of some of these filiform processes, cyclic changes in the appearance, resorption and reappearance of excrescences on the filiform processes, and changes in size and shape of the growth cones. These findings are discussed in the context of the role played by the Bergmann glia cells in the postnatal developmental events in the cerebellum, and the dynamic nature of differentiation of their processes.


Morphological characteristics of dendrite bundles in the lumbar spinal cord of the rat. The finding of motoneuron dendrites organized into small compact bundles in cats, monkeys and pigs suggested that a study of this phenomenon in rats should be undertaken. An analysis was performed with electron microscopy, light microscopy and Golgi methods. An extensive dendrite bundle organization was found in the sixth lumbar segment of the spinal cord. Two discrete bundles were localized bilaterally: a lateral bundle in the ventrolateral gray substance, and a medial bundle in the ventral funiculus. The lateral bundle was found to consist of longitudinally oriented dendrites, neurocytons, glial cells and capillaries. As many as 1678 closely packed dendrites were observed in the lateral bundle. The medial bundle contained dendrites directed across the midline and also longitudinally oriented dendrites. Neurocytons in the medial dendrite bundle were found singly or in clusters, and many radiating bundles of dendrites were observed projecting toward the lateral bundle. Golgi analysis confirmed that neurons in the lateral bundle had most of their dendrites oriented longitudinally. It was possible to trace several dendrites into the lateral bundle from dorsally and medially lying neurons. Electron microscopy substantiated the fact that the bundles were composed of dendrites. It also revealed numerous dendrodendritic and dendrosomatic contacts which were desmosomal in type as well as an abundance of small unidentified processes. Various functions which have been attributed to the dendrite bundles are discussed.


Localization of cholinergic muscarinic receptors in rat brain by light microscopic radioautography. Injection of a potent, cholinergic muscarinic antagonist, [3H]3-quinuclidinyl benzilate ([3H]QNB), results in a localization of the drug to muscarinic receptors in rat brain. The distribution of these drug receptors was examined in various brain regions previously thought to contain cholinergic neurons. They were localized to dendritic regions in the hippocampus, corpus striatum, nucleus accumbens and cerebral cortex. Particularly in the hippocampus, the receptor distribution may correspond to that for cholinergic nerve terminals.


Simulation of phase-dependent pattern changes to perturbations of regular firing in crayfish stretch receptor. A comparison was made of responses of a repetitively firing neuron to perturbations imposed in an ongoing steady firing pattern with those predicted by a model termed the 'active pacemaker model' and by a simpler 'integrate-and-fire' model. The active pacemaker model simulates the kinetics of processes such as active response generation and electrogenic sodium pumping which govern the membrane potential trajectory between a reset-point following an impulse and threshold for the next impulse. Responses of the crayfish stretch receptor neuron (MRO) and of both models were studied for both abrupt steps and square pulses of current, both hyperpolarizing and depolarizing, as a function of phase of the start of the stimulus in the normal interspike interval. Physiological results are consistent with a substantially weaker effect of a perturbation delivered earlier in the interspike interval as compared to the same one given later. The active pacemaker model successfully simulates several of the prominent results of the physiology (though by no means all), while the linear integrate-and-fire model is less successful.


Simulation of network activity in stomatogastric ganglion of the spiny lobster, Panulirus. We have compared experimental and model studies on the rhythmic activity of the lobster stomatogastric ganglion. Both the pyloric and gastric mill systems were simulated using a physiologically based network model. In the pyloric simulation the known synaptic connectivity of the 3 principal cell types in the pyloric rhythm was found to be sufficient to produce the correct sequence of cyclic bursting activity over a substantial range of parameter values, even though we did not simulate the known endogenous oscillatory driver potential of one of the cell types. It is not yet known whether the synaptic inhibition in the real system is in the right range to cause cyclic bursting in the absence of the driver potential, but the synaptic connectivity does appear to reinforce the cyclic pattern. Simulations were also done with alternative connectivity schemes to determine which synapses appear essential to generate the correct bursting sequence (in the absence of endogenous bursting activity). Other, more complex, systems simulated were: (1) all 5 cell groups of the pyloric system, and (2) the cells responsible for movement of the lateral teeth in the gastric mill. In both cases good qualitative agreement was achieved between model and real systems.


Morphine and pain: effects on aspartate, GABA and glutamate in four discrete areas of mouse brain. Experiments were performed to evaluate the effects on the levels of aspartate, GABA and glutamate in the periaqueductal central gray matter, hypothalamus, midbrain reticular formation and cortex of mouse brain following various treatments. The results indicate that only glutamate among the 3 neurohumors is systematically altered relative to the experimental manipulations. Moreover, among the 4 brain areas examined, the data implicate only the periaqueductal central gray matter as a locus of morphine's antinociceptive action. Morphine also appears to produce a drug-specific effect in hypothalamus which, however, is not analgesia-related. There were no significant pain, stress or drug-related effects on the levels of glutamate in either the midbrain reticular formation or the cortex.


Gustatory neural coding in the pons.

Gustatory neural coding in the pons. Third-order neurons from the pontine taste area (PTA) were analyzed in accordance with the across-fiber pattern theory of gustatory neural coding. Single neuron responses, evoked by chemical stimulation of the tongue, were recorded from the PTA of acute Nembutalized rats. They reveal that PTA neurons are broadly sensitive to stimuli representing the 4 putative basic taste qualities. Of 35 neurons, 33 responded to at least 3 of the 4 quality classes. Time course analyses indicate that stimuli which are shown to be alike in behavioral studies exhibit similar temporal response sequences. Correlations between all possible pairs of response patterns indicate that like-tasting chemicals elicit similar profiles of activity across the neural population. A multidimensional analysis indicates that three underlying physico-chemical dimensions (as yet undefined) bear upon the neural responses. In certain of their response properties, PTA neurons are like those of the (second-order) solitary nucleus; in other respects they auger the characteristics seen in the (fourth-order) thalamic neurons. It is concluded that the PTA is functionally as well as anatomically intermediate between the solitary nucleus and thalamus in the taste processing chain.


Varying changes in heart rate produced by nociceptive stimulation of the skin in rats at different temperatures. The effect of nociceptive stimulation of various skin areas of the neck, chest and abdomen on the heart rate was examined in anesthetized rats with the cord intact and in acute spinal rats, at different body temperatures. In the anesthetized rats with the cord intact, the stimulation on the neck, chest and abdominal skin areas caused reflex changes in heart rate. At a rectal temperature of 38.0-38.9 degrees C the response was usually an increase in heart rate, whereas the response at 36.0-36.9 degrees C was a decrease. The heart rate reflex response at 37.0-37.9 degrees C was a monophasic increase or decrease, or a biphasic initial decrease followed by an increase. The reflex increase or decrease in heart rate produced by cutaneous stimulation was mediated by a reflex increase or decrease in the efferent discharges of the cardiac sympathetic nerve. In acute spinal rats, only stimulation on the chest skin area, at a rectal temperature of 36.0-38.9 degrees C, would always produce a reflex increase in heart rate. This reflex increase in heart rate was also produced by an increase in efferent discharges of the cardiac sympathetic nerve.


Regional study of cerebral ventricle sensitive sites to angiotensin II. Angiotensin II injected in small doses into the cerebral ventricles produces an increase in blood pressure and drinking behavior. The site of action for both of these effects was studied in 3 main experiments. (1) The response to several doses of angiotensin delivered to each ventricle was investigated with multiple ventricular cannulation. This revealed that the rostral ventricular system was involved in angiotensin II mediated responses. (2) CSF flow was limited by plugging specific anterior and posterior ventricular regions and then testing for angiotensin II induced drinking and pressor responses. This technique showed that the ventral anterior third ventricle must be reached by the peptide in order to produce either blood pressure or drinking effects. (3) In order to separate pressor components due to vasopressin release and sympathetic activation, hypophysectomized rats were also tested. The experiment showed that the pressor response to intraventricular angiotensin II is due to both sympathetic and pituitary hormonal components and both are dependent on sites sensitive to angiotensin in the anterior third ventricule. The ventral anterior third ventricle or periventricular tissue surrounding it seems to be essential for both blood pressure and drinking responses to intraventricular angiotensin II.


Uptake and release of calcium by rat brain synaptosomes. Rat brain synaptosomes, prepared by discontinuous Ficoll density gradient centrifugation, accumulated 45Ca during brief incubations in modified Krebs-Ringer media. Uptake of 45Ca was increased by 5 mM glutamate and 50 mM KCl, conditions that depolarize nerve cells; uptake of 22Na was also increased by these agents. With 0.2 mM diphenylhydantoin, the increased 45Ca uptake due to KCl was diminished, whereas that due to glutamate was less affected; conversely, with 0.15 muM tetrodotoxin the increased 45Ca uptake due to glutamate was diminished, whereas that due to KCl was less affected. Both diphenylhydantoin and tetrodotoxin diminished the augmented uptake of 22Na due to KCl and glutamate; thus the increased uptake of 45Ca under depolarizing conditions may be dissociated from the increased influx of sodium. Ruthenium red decreased the uptake of 45Ca under all conditions, as did procaine and the lanthanide Pr3+. Neither 5 mM glutamate nor 50 mM KCl increased 45Ca uptake by brain mitochondria under comparable experimental conditions, whereas ATP increased the uptake by mitochondria but not that by these synaptosomes. Altering the sodium gradient by equimolar substitution of lithium or choline for sodium in the medium increased 45Ca uptake, whereas 22Na uptake was decreased. Inhibiting the sodium pump by ouabain or strophanthidin also increased 45Ca uptake, and increased 22Na uptake as well. The increased uptake of 45Ca induced by ouabain was inhibited by diphenylhydantoin and tetrodotoxin. Measurements of the total calcium content showed that conditions producing an increased uptake of 45Ca also produced a net uptake of calcium, rather than merely accelerating a 45Ca-40Ca exchange. Experiments measuring the loss of previously accumulated 45Ca showed that directly decreasing the sodium gradient or inhibiting the sodium pump slowed the loss of 45Ca. These data are considered in terms of calcium influx through 'leak' pathways and gated channels (sensitive to membrane depolarization) and of net efflux dependent on a coupled sodium-calcium exchange mechanism.


Denervation in the primary olfactory pathway of mice. III. Effect on enzymes of carnosine metabolism. Carnosine (beta-Ala-L-His) is localized within the receptor neurons of the primary olfactory system. Carnosine synthetase, the enzyme responsible for its synthesis, is found in the primary olfactory pathway of the mouse at activities higher than that found in other body tissues and brain regions. Carnosinase, the degradative enzyme, is present at high activities, only in the olfactory epithelial portion of this pathway. Peripheral deafferentation or central denervation cause a selective decrease in the activity of carnosine synthetase in the reciprocal portion of the primary olfactory system implying specific localization within the receptor neurons. These data are consistent with a role for the dipeptide carnosine in olfactory neural transmission.


A comparison of the osmotic pressures along the digestive tract of the domestic fowl and the rabbit. 1. The osmotic pressures of the contents of the alimentary tract from the adult hen and cockerel and rabbit were measured. 2. In the rabbit osmolality of the fluids from the different segments of the digestive tract was similar (331 &/- 12 mOm) and slightly hypertonic to blood plasma (297 &/- 3-12 mOsm). 3. In the hen osmotic pressures were: crop 537, gizzard 312, duodenum 571, proximal jejunum 650, distal jejunum 573, proximal ileum 514 and distal ileum 451 mOsm. Only osmolality of the crop contents was influenced by egg formation. 4. In the cockerel osmotic pressure in the alimentary tract followed the same pattern as the hen and was modified by the time of day. 5. Plasma osmolality in the fowl was about 320 mOsm. Absorption of water across the proximal jejunum is achieved therefore against a gradient of about 330 mOsm in the female and 420 mOsm in the male fowl.


Ionic constituents and osmolality of the small intestinal fluids of the laying hen. 1. The osmotic pressure of the liquid phase of the contents of the small intestine is always hypertonic to plasma and not affected by egg formation. 2. Chloride concentration is higher during shell calcification, sodium and calcium concentrations increase at the end of shell deposition while calcium concentration shows a cyclic variation with a maximum 18 h after ovulation. 3. The relationships between the ions and water of the duodenum and upper jejunum are modified by egg formation: the apparent reduction of Na+ and W+ is compensated by an increase in Ca2+. 4. It is concluded that egg formation acts on the intestinal composition via the proventriculus and gizzard rather than through a direct effect on the intestine.


Responses of laying hens to a low-protein diet supplemented with essential amino acids, L-glutamic acid and/or intact protein. 1. Three sequential experiments, each lasting 8 weeks, were carried out on 576 singly-caged light hybrids. 2. In experiment 1 egg production was 84% using a conventional control diet, 61% with a basal low-protein diet, and 79% with the basal diet supplemented with 10 essential amino acids+L-glutamic acid (GA). 3. In experiment 2 supplementation with lysine and methionine (L+M) alone increased egg production significantly from 54 to 72%, compared with 83% with the conventional diet. 4. In experiment 3 egg production was 55% with the basal diet, 71% with the basal diet+L+M, 75% with a diet containing 141 g protein/kg+L+M, and 73% with the conventional diet. 5. In all three experiments supplementation with GA alone either gave no significant response or a depression in production. 6. Daily intakes of 1-24 g nitrogen as non-essential amino acids and 13 to 14 g total crude protein per bird resulted in good egg production. Supplementation of the basal diet with L+M resulted in a daily intake of 413 mg methionine/bird day which was considered adequate, and a daily intake of 710 mg lysine which was considered slightly inadequate.


Papaveretum for anaesthesia and its comparison with morphine. Anaesthetic time/dose curves VIII. Intravenous papaveretum was used for the induction and supplementation of nitrous oxide-relaxant anaesthesia in 32 subjects undergoing major surgical operations. An anaesthetic time/dose curve was constructed from the size and timing of successive narcotic increments received by each patient and from these the loading and maintenance requirements of the group were determined. Compared with a similar series in which plain morphine was employed in the same fashion, the morphine content of papaveretum accounted for only 82 per cent of the observed anaesthetic activity. Since the remaining 18 per cent was provided by more readily inactivated alkaloids, papaveretum's therapeutic half-life was only 58 per cent (3.61 hr) of morphine (6.18 hr). All the statements outlined above proved to be statistically significant to various degrees. The advantages of a shorter acting morphine-like compound in anaesthesia are discussed.


A technique for measuring regional myocardial blood flow and its application in determining the effects of hyperventilation and halothane. A method for measuring regional myocardial blood flow with a polarographic hydrogen-clearance technique, and its experimental application in dogs, are described. Under pentobarbitone anaesthesia, flow to the superficial (3 mm) and deep (8 mm) layers of the left ventricle was not significantly different. Neither hypocapnia (PaCO2 = 24 mm Hg) nor halothane significantly altered differential distribution of blood flow to the superficial and deep layers of the myocardium. Hypocapnia was followed by a fall in myocardial blood flow (MBF) associated with increased myocardial vascular resistance (MVR). Administration of halothane 0.5 per cent at normal levels of PaCO2 led to a fall in MBF of approximately 20 per cent with no significant changes in MVR.


The effects of althesin and thiopentone on sympathetic and baroreflex activity. In decerebrate rabbits which were mechanically ventilated, both Althesin and thiopentone depressed preganglionic sympathetic activity and arterial pressure. Conduction through central baroreceptor pathways, tested by depressor nerve stimulation, showed a selective inhibition of the heart rate response by both agents. Effects were similar with Althesin injection in animals which were lightly anaesthetized with pentobarbitone. Depression of the arterial pressure and sympathetic components of the baroreceptor reflex was apparent only with high doses.


Screening of malignant hyperthermia susceptible families by creatine phosphokinase measurement and other clinical investigations. We investigated 56 families afflicted with malignant hyperpyrexia. One hundred and twenty-four individuals within these families had had an episode of malignant hyperthermia, of whom we saw seventy-two. Serum creatine phosphokinase (CPK) was statistically higher in affected individuals and in close relatives than in normal volunteers. The magnitude of the serum CPK elevations varied significantly between families. While in some families the serum CPK was clearly elevated in affected individuals, in other families the serum CPK was normal or only moderately or inconsistently raised. In these latter families serum CPK measurement was therfore of little or no value in identifying afflicted members. The incidence of musculoskeletal abnormalities was greater in affected individuals and in close relatives than in the general population. Thus, the concomitant individual belonging to a family known to be susceptible to malignant hyperthermia was a better indicator of the MH trait than was the presence of only one of these parameters. For reasons which we do not fully understand, MHS individuals were found to require fewer anaesthetics than normal persons. The incidence of MH crises within each family fell significantly following investigation, counselling, and issuance of Medic-Alert bracelets.


Acute febrile reaction complicating spinal anaesthesia in a survivor of malignant hyperthermia. A case report is presented of a survivor of malignant hyperthermia who suffered an acute febrile episode during the course of a spinal anaesthetic. It is suggested that the extreme degree of intra-operative anxiety may have triggered this event.


Radioimmunoassay of antidiuretic hormone during morphine anaesthesia. The effect of morphine anaesthesia on plasma antidiuretic hormone levels was studied in seven adult patients. Measurements of ADH showed no significant change with morphine and 50 per cent nitrous oxide. Significant elevation occurred with surgical stimulation as previously reported. Changes in urine flow with high doses of morphine are then not ADH related.


The effects of large doses of fentanyl and fentanyl with nitrous oxide on renal function in the dog. Renal effects of large doses of fentanyl (1 mg/kg) were determined in 14 mongrel dogs before and after addition of 50 per cent nitrous oxide. Fentanyl significantly increased urine osmolarity and decreased urine output and free water clearance but did not change inulin or PAH clearances. The arterial blood pressure and cardiac output were significantly decreased after 0.1 mg/kg fentanyl and these changes were then maintained during the remainder of the study period. Addition of nitrous oxide produced no further changes in cardiac output and arterial blood pressure but did increase urine output, PAH, inulin and free water clearances and decreased urine osmolarity. These data demonstrate that high doses of fentanyl have significant antidiuretic properties in the dog and these probably are related to the release of antidiuretic hormone. Our results also indicate that addition of nitrous oxide reverses fentanyl induced antidiuresis.


Inhibition of the cardiovascular effects of acupuncture (moxibustion) by propranolol in dogs during halothane anaesthesia. Acupuncture by electrocautery, moxibustion, at Jen Chung (Go-26) acupoint produces a sympathomimetic effect on the cardiovascular system of dogs under halothane anaesthesia (MAC I). This effect is manifest by significant increase in cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure while total peripheral resistance is significantly decreased during a two-hour period of observation. Pretreatment with the beta blocker, propranolol, caused a significant decrease in cardiac output, heart rate, mean arterial pressure and pulse pressure while total peripheral resistance is significantly increased. Similar responses were observed when propranolol was administered without moxibustion at Jen Chung (Go-26).


Anaphylaxis to thiopentone: a case report. A case of anaphylaxis to thiopentone is reported and its immediate treatment with epinephrine is emphasized. Other reported cases of allergic reaction to thiopentone and to muscle relaxants are reviewed. There are no reliable diagnostic tests for allergy to these agents.


Doppler determined blood pressure recordings: the effect of varying cuff sizes in children. Ten children ages 12 months to 14 years were studied to determine the effect of cuff size on blood pressure determined by the Doppler ultrasonic technique compared to blood pressure recordings by the auscultatory method. It was found that Doppler determined blood pressure varied with cuff size as it does with the auscultatory method. Too small a cuff will give an artificially high recording while too large a cuff causes too low a recording. The effect of the large cuff is less marked than the effect of too small a cuff.


Airway obstruction with cuffed flexometallic tracheal tubes. The occurrence of an airway obstruction with a cuffed flexometallic tracheal tube is reported. The cause of the obstruction is attributed to internal herniation of the distal extremity of the tube secondary to diffusion of anaesthetic gases into the tracheal tube cuff and subsequently between the two layers of the distal extremity of the tube. Methods to avoid overdistension of the cuff volume are described.


Identification of the mouse chromosomes by microdensitometry. Densitometric analysis has been performed on mouse chromosomes from "in vivo" preparations stained with Giemsa after trypsinisation. The characteristic curves obtained by analysing the same chromosome after different durations of trypsinisation suggest that a trypsinisation step is not always necessary to get an analysable banding pattern. The best results are obtained when the chromatids are long and closely appressed and by analysing the positive photomicrographs.


Geographic variation of the chromosomal polymorphism in Drosophila flavopilosa. Natural populations of the Chilean species Drosophila flavopilosa Frey are polymorphic for the banding sequences in the fifth chromosome due to the existence of four paracentric inversions. Qualitative analysis of the polymorphism demonstrated that there are seasonal fluctuation and geographic variations of two kinds: altitudinal gradients and a north-south gradient. In addition, the northernmost and southernmost samples examined are polymorphic only for one inversion (inversion "B"). In the light of previous experimental evidence, it was concluded that the seasonal fluctuations and elevational differences are probably controlled by weather conditions, especially temperature. However, the observed differences between the central and marginal populations require another type of interpretation, similar to that postulated for other species that exhibit the same pattern of chromosomal variation. A photomicrographic map of the Standard banding pattern of the salivary gland polytene chromosomes of D. flavopilosa is presented.


Sex chromatin and chromosome numbers in Lepidoptera. Three classes of sex chromatin (SC) distribution have been encountered in a sample of Canadian Lepidoptera. In 78 of the 103 species examined, females were SC positive and males were SC negative. In another 24 species, females and males were SC negative. Females and males of a single species, Eucordylea resinosae, had two equal-sized SC bodies in interphase nuclei. In no species were females found to be SC negative and males SC positive. Usually presence of SC indicates an XX male and XY female sex determining mechanism, and its absence, XX male; XO female, but the exceptional occurrence of SC in females and males of a species suggests the need for caution in too universal an application of this interpretation. Chromosome numbers have also been determined for 53 of the 103 species. Male haploid numbers ranged from 11 to 61, but 30 was most frequently encountered.


The synthesis of compound autosomes in the Australian sheep blowfly Lucilia cuprina. The synthesis of the first compound chromosome strain in Lucilla cuprina (Diptera: Calliphoridae) (Weidemann) is described. Crosses between the compound chromosome strain and a chromosomally normal strain produce no offspring, whereas crosses between compound chromosome-bearing individuals are fertile. Cytological evidence is presented that compound chromosome arms assort art random with respect to one another during spermatogenesis.


Amylase isozymes in the mosquito, Culex tritaeniorhynchus. A survey of laboratory stocks of Culex tritaeniorhynchus Giles has uncovered the presence of four electrophoretic variants and one apparent null allele of amylase. Linkage experiments with heterozygous males indicate that amylase is sex-linked. The gene sequence is w (white eye) - Amy (amylase) - M (sex), and the recombination frequencies are: w - Amy = 6.02%, Amy - M = 1.35% and w - M = 7.37%.


Evidence for nuclear restriction of supersuppressor gene products in Neurospora heterokaryons. It was demonstrated that the gene products of the three ssu loci cannot enter the transcription/translation system coded by the other component nucleus in a heterokaryon. In such a situation, dominance or recessiveness cannot be established, and simple dominance tests are meaningless.


The genetics of black larva, an autosomal recessive lethal mutation located on chromosome 3 in the mosquito Anopheles albimanus. A spontaneous autosomal recessive lethal mutation, black larva (bl), producing black pigmented larvae that die during the 4th larval instar has been discovered in the mosquito Anopheles albimanus Wiedemann. Genetic investigations using two Y-autosome translocations and a 3rd chromosome dominant marker, St indicate that bl is located on chromosome 3 at a distance of 15 map units from St.


Chromosome structure in Chilocorus (Coleoptera: Coccinellidae). II. The asynchronous replication of constitutive heterochromatin. Chromosome replication has been analysed in four species of Chilocorus. In C. ORBUS Csy., C. tricyclus Smith, and C. hexacyclus Smith, centric regions of all chromosomes are last to replicate, preceded in order by heterochromatic arms and euchromatic arms. In C. stigma Say, very late replication of centric regions can be detected only in otherwise wholly euchromatic chromosomes (= monophasics); in chromosomes with one arm heterochromatic ( = disphasics), these arms are last to replicate. Based on pachytene bivalent morphology and chromosome banding patterns, and supported by autoradiographic data, models are presented for the general organisation of Chilocorus chromosomes. All chromosomes in the first three species are subdivided into euchromatic arm, centric heterochromatin, and either a second euchromatic are (monophasics) or a heterochromatic arm (diphasics). Chilocorus stigma diphasics apparently lack distinct centric organisation, and are therefore divided into euchromatic and heterochromatic arms only.


Studies of the herbicide paraquat. I. Effects on the cell cycle and DNA synthesis in Vicia faba. Vicia faba root tips were exposed to concentrations of paraquat ranging from 10-3M to 10-6M. There was a statistically significant inhibition in 3H-thymidine incorporation, and, therefore, presumably of DNA synthesis by all concentrations of paraquat studied. All concentrations of paraquat also had a statistically significant effect on the percentage of cells in division at various hours following paraquat treatment. At 10-3M and 10-4M paraquat there was an almost total inhibition in the number of cells moving from the S period and through the G2 period and into division. Cells treated with 10-6M paraquat, however, did move through the G2 period and into division. A concentration of 10-4M paraquat did not result in an increase in chromosome aberrations.


Effects of furosemide and chlorothiazide on blood pressure and plasma renin activity. Short (2 weeks) and long (12 weeks) term effects of furosemide and chlorothiazide on blood pressure, plasma renin activity, and uric  acid concentration were studied in 69 hypertensive patients. Both treatments caused significant reductions in blood pressure and increases in plasma renin activity and uric acid at 2 and 12 weeks in 6) normal renin patients; there was no difference between the effects of furosemide and that of chlorothiazide. Reduction in blood pressure in eight low renin patients who showed smaller changes in plasma renin activity and uric acid was not significant at 2 weeks but significant after 12 weeks of treatment.


Increase of intravascular blood volume in Ischaemic heart disease. Circulating blood volume, cardiac index, heart rate, and ejection rate were measured in patients with angina pectoris. The controls and the patients were divided in sub-groups of those under 45 and over 45 years of age. The investigation was carried out using the isotope method. A significant difference was observed in the value of intravascular blood volume at rest between the controls and patients with ischaemic heart disease unrelated to anginal attack. The blood volume was 5.6 litre in the control group and 6.4 litre in patients with ischaemic heart disease. Exercise tests produced further increases during attack in the blood volume of angina patients. A significant increase of blood volume after moderate exercise was also observed in patients under 45 with ischaemic heart disease but without angina. It is suggested that the increase of intravascular blood volume plays a part in the pathogenesis of angina pectoris.


Right atrial monophasic action potential and effective refractory periods in relation to physical training and maximal heart rate. The monophasic action potential (MAP) and the effective refractory period (ERP) of the right atrium were determined in eight healthy volunteers before and after hard physical training. The duration and amplitude of the MAP increased in seven individuals after training. ERP showed no consistent changes. One possible explanation of the findings is an accumulation of intracellular potassium. The duration of the MAP was well correlated to maximal heart rate.


Dopamine beta-hydroxylase release during hypertension from sympathetic nervous overactivity in man. In subjects with cervical spinal cord transections, hypertension due to sympathetic nervous overactivity resulted in a rise in plasma dopamine  beta-hydroxylase (DbetaH), the peak occurring 3 to 5 min after the peak blood pressure response. This indicates that DbetaH may be released from sympathetic nerve terminals during sympathetic activity in man, and emphasizes the importance of sample timing in acute studies on DbetaH.


Cardiovascular reflex responses to apnoeic face immersion and mental stress in diabetic subjects. The cardiovascular reflex responses to apnoea accompanied by immersion of the face in water and to mental stress, have been investigated in 21 diabetic subjects. Apnoeic face immersion caused bradycardia and forearm vasoconstriction (in seven subjects), bradycardia and forearm vasodilation (three subjects), tachycardia and forearm vasoconstriction (three subjects), or tachycardia and forearm vasodilatation (eight subjects). Mental stress evoked a tachycardia and forearm vasodilatation in all subjects. The abnormalities in the responses to apnoeic face immersion are most readily accounted for by loss of vagal and/or vasoconstrictor function.


Venous pressure-volume relation and calf blood flow determined by changes in posture. The volume capacity of the venous system in the calves of 70 normal subjects was determined by passive and active changes in posture, using mercury-in-rubber strain gauges. The mean volume capacity was 1.26% (SD 0.39%) at a venous pressure of 0 kPa (o mm Hg) and 2.05% (SD 0.70%) at 1.60 kPa (12 mm Hg). With this method the blood flow in the calves at rest was measured without venous occlusion: 2.84 ml-100 ml-1/min (SD 1.20). During interpolated venous occlusion the mean blood flow was 2.67 ml-100 ml-1/min (SD 1.21). The pressure-volume relation over the pressure range 0 to 9.31 kPa (0 to 70 mm Hg) was determined in seven normal subjects.


Effect of heart rate on regional coronary blood flow. The effect of tachycardia on the distribution of coronary blood flow was studied in the dog using the radioactive microsphere technique. Increasing heart rate from 1.7 to 3.0 Hz produced an increment of flow to the inner and outer layer of both ventricular walls. However, the flow ratio, inner layer to outer layer, increased in the right ventricular wall and decreased in the left wall. Measurements performed in ventricular regions with previous vasodilatation and during right ventricular hypertension revealed that the comparatively larger vasodilatation reserve of the right ventricular subendocardium is due to the lower pressure this ventricle develops normally.


The renin-angiotensin system, dietary salt, and increased sensitivity to noradrenaline in mesenteric vasculature preparations from renal/salt hypertensive rats. Exogenous angiotensin II causes noradrenaline supersensitivity in rat mesenteric vasculature preparations. The noradrenaline supersensitivity of tissues from renal/salt hypertensive rats, with low plasma renin activity, is not caused by endogenous angiotensin II since it was unaffected by Sar1 Ileu8 angiotensin II. Dietary salt-loading caused a small increase in noradrenaline sensitivity.


Intracellular electrophysiological alterations in canine cardiac conducting tissue induced by aprindine and lignocaine. The effects of aprindine and lignocaine (lidocaine USP) were compared on intracellularly recorded potentials from normal canine conducting tisues. Only aprindine produced marked depression of the maximum rate of rise (Vmax) of action potentials elicited at normal cycle lengths (1000 ms). Both compounds, however, produced enhanced depression of Vmax at short cycle lengths or at short S1-S2 coupling intervals at normal membrane resting potential. Both lignocaine and aprindine shorten the action potential duration (APD) and effective refractory period (ERP) but increase the EPR/APD ratio. These effects are easily reversible upon perfusion with drug-free solution only in the case of lignocaine.


Effect of reperfusion on myocardial infarct, and the accuracy of estimating infarct size from serum creatine phosphokinase in the dog. This study was designed to determine the effect of coronary reperfusion on (1) myocardial infarct size and (2) the accuracy of previously reported methods for estimation of infarct size serum creatine phosphokinase (CPK) values. Thirty mongrel dogs, chronically prepared, were studied in the awake state, and were divided into four groups according to the period or left circumflex coronary artery (LCCA) occlusion. Group 1: permanent occlusion (24 h) in nine dogs; group 2: 45 min occlusion (eight dogs); group 3: 1 h occlusion (five dogs); and group 4: 3 h occlusion (eight dogs). Serial blood samples were drawn for 24 h following the beginning of occlusion and were used to determine total and isoenzyme levels of CPK, and lactic dehydrogenase isoenzymes. All dogs were sacrified 24 h after the beginning of occlusion and were anatomically examined. The extent of anatomical myocardial infarction was determined  and compared with the extent of myocardial infarction as estimated from serial serum CPK values. Total serum CPK increased significantly in all groups and was associated with the appearance of CPK-MB isoenzyme and an increase in LDH1,2 (LDH1 greater than LDH2) in most dogs. Total serum CPK increased within an hour after reperfusion and the mean values in groups 2, 3, and 4 were significantly high (P less than 0.05) than serum CPK values in group 1 in the period from 110 min to 4 after occlusion. These data demonstrate that reperfusion after 45 min to 3 h of coronary occlusion results in an earlier appearance of total serum CPK. The anatomical infarction in group 1 averaged 28% +/- 3% (SEM) of the total heart and was significantly larger than infarct size in all groups with reperfusion. In contrast, estimated infarction calculated from total CPK in group 1 was not significantly different from the reperfused groups. Although there was correlation between estimated and anatomical infarction, the data in each group showed that anatomical infarct size could not be accurately estimated from total serum CPK.


Effects of hypertensive plasma on the responses of an isolated artery preparation to noradrenaline. The effect of hypertensive plasma on the responses of an isolated artery preparation to noradrenaline were studied. In addition, because of the association between hypercholesterolaemia and hypertension, the effect of pure cholesterol and low density lipoprotein on the arterial responses to noradrenaline was also investigated. Both hypertensive plasma and low density lipoprotein potentiated the responses of the arterial preparation to noradrenaline.


Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the occurrence of unidirectional block, as studied with multiple microelectrodes. Periods of tachycardia were induced in isolated segments (15 X 15 mm) of rabbit left atrium by local application of a properly timed premature stimulus. We used a special device for multiple synchronous microelectrode recordings of responses of more than 100 fibers during the initiation of tachycardia. We clearly demonstrated circus movement of the impulse through a small area of atrial muscle as the underlying mechanism. The premature impulse was conducted antegrade in only one direction, whereas in the other directions antegrade conduction failed. The local responses of the fibers in the blocked area served as a temporary obstacle for return of the premature impulse. When these fibers recovered their excitability before extinction of the premature impulse, they were reentered in a retrograde direction, and the impulse traveled in a circular route. During the propagation of a premature beat, local block, which set the stage for circus movement, was caused by nonuniform recovery of excitability of the atrium. We related the spread of activation of a premature impulse to the naturally occurring spatial dispersion in refractory periods and found that local conduction block invariably was associated with an area of delayed restoration of excitability. Artificial induction of differences in refractory periods by regional application of carbamylcholine made it clear that a disparity in refractory periods of only 11-6 msec between adjacent areas may be sufficient to cause local conduction block of a properly timed premature impulse.


Mechanism for the postive inotropic effect of angiotensin II on isolated cardiac muscle. Angiotensin II (A II) and analogues were tested for their ability to restore electrical and mechanical activity to cardiac muscle preparations in which the fast Na+ channels had been inactivated by partial depolarization (22-27 mM K+) or by tetrodotoxin (TTX). The partially depolarized or TTX-blocked preparations were chosen because under these conditions electrical and mechanical responses are primarily Ca2+ -dependent. In depolarized rabbit right atria, A II restored spontaneous mechanical and electrical activity (measured by both intracellular and extracellular recording techniques). The frequency of action potential discharge was concentration-dependent; the threshold concentration of A II was 10(-10) M, the ED50 was 8 X 10(-9) M, and the maximum effect was observed at 5 X 10(-8) M. In contrast, depolarized guinea pig atria were insensitive to A II, Sar1-angiotensin II, and des-Asp1-angiotensin II, even at concentrations as high as 10(-5) M. Rabbit papillary muscle (TTX-blocked), embryonic (18-day) chick heart (partially depolarized) and chick heart reaggregates (TTX-blocked) responded similarly to rabbit atria in that A II (9.6 X 10(-7) M) restored both electrical and mechanical activity. We found that in these preparations the action of A II was unaffected by propranolol (5.0 X 10(-6) M to 5.0 X 10(-5) M) but was blocked by Mn2+ (10(-3) M), D-600 (1 X 10(-7) g/ml) and the specific A II antagonists Sar1-Ala8-angiotensin II (P-113) (5.0 X 10(-5) M) and Sar1-Ile8-angiotensin II (5.28 X 10(-5) M). We conclude that the positive inotropic effect of A II on the myocardium is due to its ability to increase transmembrane ion movements in or through the cell membrane. The ability of Mn2+ and D-600 to block this effect suggests that this ion movement is via the so-called "slow channels."


Response of aldosterone and blood pressure to angiotensin II infusion in anephric man. Effect of sodium deprivation. Angiotensin II, infused intravenously, increased plasma aldosterone concentration in two of six anephric subjects taking their usual dietary quantities of sodium. After 3 days of dietary sodium restriction and weight-reducing hemodialysis, the aldosterone response to infused angiotensin II in the two previously reactive subjects was enhanced, while the four previously unreactive subjects also showed a rise in plasma aldosterone. Before and after sodium depletion the anephric subjects were less responsive than normal subjects. Even when sodium-depleted, the anephrics showed no further rise in plasma aldosterone when arterial plasma angiotensin II was increased by infusion to concentrations greater than 50-199pg/ml, in contrast to sodium-depleted normals who show progressive aldosterone responses with plasma angiotensin II concentrations up to at least 370pg/ml. Before the infusion of angiotensin II, arterial plasma renin, angiotensin II, and aldosterone were detectable in the anephrics, but were unchanged by dietary sodium restriction or weight-reducting hemodialysis. Sodium depletion caused significant falls in weight, plasma sodium, and blood pressure, but no changes in plasma potassium or cortisol. Increases in blood pressure in relation to increments of arterial plasma angiotensin II were unaffected by sodium depletion, as might be expected in the absence of a rise in endogenous angiotensin II.


Renin release by rat kidney slices incubated in vitro. Role of sodium and of alpha- and beta-adrenergic receptors, and effect of vincristine. The role of sodium concentration, of alpha- and beta-adrenergic receptors, and of a microtubular inhibtor (vincristine) on renin release was studied in rat kidney slices in vitro. Renin release was an active, linear, and temperature-dependent process. Kidneys from young rats released much more renin than those from adults. Lowering sodium concentration inhibited renin release by one-half, even when osmolality was kept constant. Isoproterenol (10(-8) to 10(-5) M) stimulated renin release significantly in a partially dose-related manner. dl-propranolol inhibited this stimulation. Significant (P less than 0.05) inhibition of renin release was induced by l-epinephrine or l-norepinephrine (10(-5) M). In the presence of an alpha-receptor blocking drug, phenoxybenzamine (10(-5) M), inhibition no longer occurred with epinephrine and stimulation was observed with l-norepinephrine. Vincristine (10(-5) M) did not affect renin release when slices from the kidneys of normal rats or adrenalectomized, sodium-depleted rats were incubated, but significantly inhibited (P less than 0.01) release that had been stimulated in vitro by isoproterenol. These results suggest to us that there may be (1) a direct or indirect (mediated through the macula densa) effect of sodium on juxtaglomerular cells, (2) an inhibitory role for alpha-adrenergic receptors on renin release, in addition to the stimulatory role of beta-receptors, (3) possible participation of microtubules in isoproterenol-stimulated renin release, and (4) an alternative mode of secretion of renin under stimulation by adrenalectomy and salt depletion.


Plasma catecholamines during paroxysmal neurogenic hypertension in quadriplegic man. Blood pressure, heart rate, and plasma catecholamine levels were measured in 16 quadriplegic subjects with physiologically complete cervical spinal cord transections above the level of the sympathetic outflow, and in 15 normal subjects (controls). In the quadriplegics the average resting blood pressure was 107/59 (mean, 75) mmHg, heart rate was 65 beats/min, and plasma norepinephrine (NE) and epinephrine (E) levels were 0.05 and 0.005 ng/ml, respectively. In the controls average resting blood pressure was 117/79 (mean, 92) mmHg, heart rate was 61 beats/min, and resting plasma NE and E levels were 0.20 and 0.06 ng/ml, respectively. Resting blood pressure and plasma NE and E levels were significantly lower in the quadriplegics (P less than 0.01, less than 0.001, less than 0.001, and less than 0.001, less than 0.001, respectively)  than in the controls. In the quadriplegics, neurogenic hypertension was induced by bladder and muscle stimulation. This resulted in a marked elevation of both systolic and diastolic blood pressure (from an average of 109/60 (mean, 75) to 168/87 (mean, 114) mmHg) as a result of uninhibited sympathetic nervous activity through the isolated spinal cord. Plasma NE consistently rose, from an average of 0.05 to 0.16 ng/ml (P less than 0.001). There was significant linear relationship between plasma NE and mean blood pressure (P less than 0.001). In the quadriplegics infusion of l-norepinephrine to raise the blood pressure to comparable levels (from 105/58 (mean, 74) to 183/93 (mean, 123) mmHg) resulted in plasma NE levels approximately 21 times higher than during muscle and bladder stimulation. It is possible that the lower resting arterial blood pressure and plasma NE and E levels in the quadriplegics in comparison to normal subjects may reflect diminished resting sympathetic nervous activity. The rise in blood pressure following increased sympathetic nervous activity was accompanied by an elevation in plasma NE. The hypertension was not secondary to the rise in plasma NE. Plasma NE in these subjects appears to be a reliable index of prevailing sympathetic nervous activity.


The low frequency dynamic viscoelastic properties of human aortic valve tissue. Membranous samples of human aortic valve cusps were subjected to sinusoidal fluid pressure variations (frequency range, 0.5-5 Hz) to assess their dynamic viscoelastic properties. The storage (elastic) and loss (viscous) moduli and phase lag between the stressing function and response were found to be independent of the frequencies applied. The respective average values were 1.35 (SE = 0.06) X 10(8) dynes cm-2, 4.14 (SE = 0.28) X 10(6) dynes cm-2, and 0.033 (SE = 0.002) rad. The small phase lag indicates that the tissue would recover almost completely to its original state on removal of any applied stress, and this and the relatively low extensibility should be considered in the design of leaflet-type valve prostheses. The storage modulus of the aortic valve cusps when compared to that of the mitral leaflet shows the mitral leaflet to be almost twice as stiff as the aortic valve cusps. This finding led us to conclude that the vibrations of these two cardiac valves alone cannot contribute in any significant way to the production of the observed lower frequency of the first and the higher frequency of the second heart sounds and that other factors must be considered to explain this finding.


Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog. Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.


The 1,2,3,4 phenomenon. Atrioventricular nodal gap in the dog. This study confirms the facility with which the so-called 1,2,3,4 phenomenon can be reproduced in intact dog hearts. When a series of three atrial premature beats (A2, A3, A4) were delivered following a constant A1-A1 drive, we demonstrated a narrow zone of A1-A3 and A1-A4 intervals in which A4 conducted to the ventricles in the presence of A3 but not in its absence. We used His bundle and multiple atrial electrograms to produce the phenomenon in nine of 16 dogs. Facilitation of conduction of A4 (1) occurred above the His bundle, (2) occurred within narrow ranges of A1-A3 and A1-A4 intervals, (3) required penetration of A3 into the atrioventricular (AV) node, (4) required critically long A2-H2 intervals, (5) always was associated with prolonged A4-H4 intervals, and (6) was limited by atrial refractoriness. An apparent or pseudo-1,2,3,4 phenomenon demostrated in five of 16 dogs occurred with (1) latency between S4 and A4, (2) a sinus nodal or atrial reentry beat, or (3) an atrial escape beat. In the absence of A3, A4 could be made to conduct by preexciting the ventricle in advance of V2. We found no evidence for dual AV nodal pathways. Our results suggest that the underlying mechanism for the 1,2,3,4 phenomenon is analogous to the phenomenon of the gap in AV conduction.


The stimulation of cardiac prostaglandin production by blood plasma and its relationship to the regulation of coronary flow in isolated isovolumic rabbit hearts. Infusion of small amounts of blood plasma into isolated, isovolumic rabbit hearts perfused with Tyrode's solution resulted in coronary vasoconstriction followed by a decrease in left ventricular developed pressure and dP/dt. Maximal effects were obtained with a perfusate plasma concentration of 1%. Increasing the plasma concentration beyond 1% did not appreciably increase the coronary vasoconstriction. During perfusion with 2% plasma, the coronary flow-oxygen uptake ratio was unchanged over a range of perfusion pressures (40-100 mm Hg) and vascular resistance increased with pressure. In the absence of plasma, the coronary flow-oxygen uptake ratio increased with pressure and vascular resistance decreased. Thus, cardiac regulation of coronary flow in response to changes in perfusion pressure occurred in the presence of plasma but not in its absence. The effects of plasma were reduced with two different inhibitors of prostaglandin synthesis (5,9,11,14-eicosatetraynoic acid and indomethacin). At a perfusate concentration of 50 mug/ml, indomethacin abolished the effects of 2% plasma. Rat stomach strip bioassay for prostaglandin activity indicated that the vasoconstrictor effect of plasma was accompanied by a 4-fold increase in the release of prostaglandin activity by the isolated hearts. The vasoconstrictor effect of plasma also was accompanied by an increase in the conversion of 3H-arachidonate to radiolabeled prostaglandins E2 and F2alpha. These results indicate that a relationship exists between a coronary vasoconstrictor in plasma, cardiac prostaglandin synthesis, and the regulation of coronary flow in response to changes in perfusion pressure in isolated rabbit hearts.


Interaction of capillary, interstitial, and lymphatic forces in the canine hindpaw. We used plethysmograph techniques to measure or calculate the tissue and capillary forces and flows (capillary pressure, tissue and plasma oncotic pressure, transcapillary pressure drop, lymph flow, and interstitial pressure) in a dog hindpaw preparation in situ at three different venous pressures (PV). Since lymph was flowing from the preparation, an isovolumetric state represented an isofiltration state rather than the conventional isovolumetric or isogravimetric state. At an isofiltration capillary pressure of 12.8 mm Hg, lymph oncotic pressure averaged 3.8 mm Hg, plasma oncotic pressure averaged 20.9 mm Hg, and tissue pressure averaged -4.7 mm Hg (PV normal). The imbalance in transcapillary forces averaged 0.5 mm Hg and represented the lymph flow contribution (lymph flow/filtration coefficient) to maintainance of the normal isofiltration state. As isofiltration capillary pressure increased to 24.9 mm Hg, interstitial fluid volume increased by 1.7 ml/100g of tissue, tissue pressure rose by 4.6 mm Hg, lymph oncotic pressure fell by 2.2 mm Hg, and the transcapillary pressure drop increased to 5.6 mm Hg (PV = 20 mm Hg). At an isofiltration capillary pressure of 38.0 mm Hg, interstitial fluid volume increased by 17.5 ml/100g, interstitial pressure rose to +10 mm Hg, lymph oncotic pressure fell to 0.5 mm Hg, and the transcapillary pressure drop increased to 6.3 mm Hg (PV = 30 mm Hg). At moderate levels of PV elevation, the transcapillary pressure drop and increased tissue pressure provided 80% of the counterbalancing tissue force, each contributing approximately 40%. At higher venous pressures, the only tissue force that opposed filtration was an increase in tissue pressure.


Regional refractoriness within the ventricular conduction system. An evaluation of the "gate" hypothesis. We studied the refractoriness of Purkinje fibers with the intent of localizing critical sites of block of premature impulses. To preserve the ventricular conducting system (VCS) nearly intact in vitro, we used a modification of the Elizari preparation. This was superfused with a physiologic salt solution. Action potential durations increased progressively from the His bundle to the distal Purkinje fibers along three pathways: (1) the main right bundle branch and moderator band; (2) the anterior border fibers of the left bundle and anterior false tendons; (3) the posterior border fibers of the left bundle and posterior false tendons. The action potential durations near the terminations of the false tendons were the longest ones found. The interior fibers of the left bundle branch had action potentials of shorter duration and greater variability than those of simultaneously activated fibers in the right bundle branch or the border fibers of the left bundle branch. Similarly, on the right side, the septal branches of the right bundle had action potentials of shorter duration than those of the moderator band. We also found that the fibers with short action potential durations provided the quickest pathways to septal myocardium. When extrastimuli were applied to the His bundle, block in a bundle branch always occurred in the proximal 1 or 2 cm of the main bundle branch. Experiments performed in vivo in which extrastimuli were delivered to the atrium or His bundle and recordings made from the terminations of false tendons and the distal ends of the main right bundle branch confirmed the finding that the critical sites of block were located in the proximal main bundle branches.


Inhibition by acetylcholine of the norepinephrine release evoked by potassium in canine saphenous veins. In the dog's saphenous vein acetylcholine inhibits the norepinephrine release caused by nerve stimulation, but not that caused by tyramine. Experiments were performed to determine whether acetylcholine affects the release of norepinephrine evoked by high K+ concentrations. We recorded changes in isometric tension of dog saphenous vein strips. Acetylcholine (5 X 10(-9) to 10(-6) g/ml) caused dose-dependent relaxations during contractions caused by K+ = 40 mEq/liter. These relaxations were not depressed by tetrodotoxin (10(-7) g/ml), which abolished the response to nerve stimulation, but were inhibited by atropine (10(-7) g/ml). Strips of saphenous veins were incubated with [3H]norepinephrine and mounted for superfusion (3 ml/min) and isometric tension recording; the total radioactivity and the amount of intact [3H]norepinephrine present in the superfusate were determined. K+ at 50 mEq/liter increased tension, total radioactivity of the superfusate, and the [3H]norepinephrine afflux; acetylocholine (10(-7) g/ml) depressed the contractions and diminished the efflux of [3H]norepinephrine. Increasing the K+ concentration from 50 to 70 mEq/liter augmented both tension and the evoked release of [3H]norepinephrine. Acetylcholine did not significantly alter the release of [3H]norepinephrine evoked by K+ = 120mEq/liter. These experiments show that acetylcholine inhibits the norepinephrine release evoked by potassium ions, as it does during nerve stimulation. The inhibition of adrenergic neurotransmission is not due to interference with action potential electrogenesis, but probably is caused by hyperpolarization of the adrenergic nerve endings.


Progressive perfusion impairment during prolonged low flow myocardial ischemia in dogs. Recent studies have shown that after total coronary artery occlusion, there is impaired "reflow" of blood accompanied by myocardial and capillary endothelial cell swelling. To investigate the effect of prolonged low flow myocardial ischemia on coronary vascular resistance, regional hypoperfusion of the distal left anterior descending coronary artery was studied in 31 autonomically blocked dogs on right heart bypass. Heart rate, aortic pressure, and, during ischemia, left ventricular end-diastolic pressure were held constant. The distal left anterior descending coronary artery was perfused at a substantially reduced perfusion pressure which resulted in an antegrade coronary blood flow that usually was between 3% and 7% (0.5-1 ml/min) of control. When relative hypothermia (33-34 degrees C) was induced in nine dogs, left anterior descending coronary artery vascular resistance did not change during 2.5-3 hours of low flow ischemia. Under euthermic conditions (37-40 degrees C) in 17 dogs there was a consistent progressive increase in distal left anterior descending coronary artery vascular resistance starting at 90 minutes (median) after onset of ischemia. By 110-140 minutes ischemic antegrade flow decreased by 35 +/- 4% (SEM) (P less than 0.01). Directionally similar flow changes were observed in six euthermic experiments using the krypton-85 washout technique. Light microscopy did not reveal hemorrhage as a cause of the increased vascular resistance. The perfusion impairment did not occur in two euthermic, nonischemic hearts. In five dogs elevation of serum osmolality by 23 +/- 11 mOsmol/liter with mannitol attenuated the progressive decrease in flow. Thus, a progressive perfusion defect exists in the ischemic low flow state in the heart which presumably contributes to the extent of eventual necrosis.


Collecting duct function in deoxycorticosterone acetate-escaped, normal, and salt-deprived rats. Response to hypervolemia. The microcatheterization technique was used to study reabsorption of fluid, sodium, and potassium in the medullary collecting duct in chronically deoxycorticosterone acetate (DOCA)-treated and salt-loaded rats, as well as in normal and chronically salt-deprived (NaD) rats, before and after infusion of donor blood (33% of estimated circulating volume). Before expansion, urinary sodium excretion was highest in DOCA rats, intermediate in normal, and lowest in low salt rats. Significant collecting duct reabsorption was found in NaD, normal, and DOCA groups. In contrast to sodium, no net transport of potassium was found in any series. During intravascular expansion, increased renal excretion of fluid and sodium was observed uniformly in both DOCA and normal groups, whereas a diuretic response was found in five of seven rats, and a natriuretic response in four of seven rats of the NaD group. Natriuresis of DOCA rats was significantly greater than that of either normal or responding NaD rats. Diuresis and natriuresis in all three series were assocaited with complete inhibition of fluid and sodium reabsorption from the lumen of the medullary collecting duct, whereas such reabsorption persisted in nonresponding low salt rats. Increased sodium excretion in DOCA rats in comparison to the other two series could be explained by enhanced intratubular delivery of the ion to the medullary collecting system. I conclude that the renal response to acute blood volume expansion is due primarily to complete inhibition of both fluid and sodium reabsorption in the medullary collecting duct, but that differences in tubular delivery may modify the resulting diuresis and natriuresis.


Noninvasive visualization of the left main coronary artery by cross-sectional echocardiography. Real time cross-sectional echocardiographic studies of the left main coronary artery (LMCA) were performed in 15 normal patients, 15 patients with angiographically proven coronary artery disease but normal left main coronary segments, three patients with greater than 75% obstruction of the left main coronary artery, and one patient with a larger aneurysm of the left main coronary artery. In normal subjects the LMCA evaginates from in inferolateral wall of the aorta. The artery appears as two dominant parallel linear echoes separated by a clear space representing the lumen of the vessel. The LMCA courses beneath the right ventricular outflow tract and can generally be followed to its expected point of bifurcation. Confirmation that this structure was in fact the LMCA was obtained by injection of cardiogreen dye directly into the LMCA in two cases and by visualization of dye in this structure following aortic flush in one case. In the three cases with obstructive lesions of the LMCA, there was an area of inward bending of the parallel vessel wall echoes resulting in varying degrees of narrowing of the arterial lumen. In the case with the aneurysmal dilatation of the LMCA, an echo-free circular bulge in the distal portion of the LMCA was recorded. This study demonstrates the fesibility of recording the left main coronary artery using the cross-sectional echocardiographic technique.


Mechanism of abnormal septal motion in patients with right ventricular volume overload: a cross-sectional echocardiographic study. To evaluate the mechanism of paradoxical septal motion in patients with right ventricular volume overload (RVVO), short axis cross-sectional, echocardiographic studies of the left ventricle (LV) and interventricular septum (IVS) were performed in 19 patients with paradoxical septal motion due to RVVO and in 20 normal subjects. Short axis study in normal subjects revealed the left ventricle to be a relatively circular structure during both diastole and systole. In patients with RVVO a change in LC diastolic shape was observed. This change in shape varied from a slight flattening of the LV and IVS during diastole to total reversal of the normal direction of septal curvature such that the IVS became concave toward the RV and convex toward the LV. During systole the LV and IVS returned to their normal relatively circular configuration. This change in LV shape from diastole to systole resulted in net motion of the IVS toward the right ventricle (paradoxically). This study therefore suggests that paradoxical septal motion in patients with right ventricular volume overload is a result of a change in the diastolic shape of the left ventricle.


The association of increased plasma MB CPK activity and irreversible ischemic myocardial injury in the dog. To evaluate the concordance between elevated plasma MB CPK and irreversible myocardial ischemic injury, coronary occlusion was induced for 10 minutes to 48 hours in 21 open chest dogs and 13 conscious animals. Results of plasma CPK and MB CPK assayed in samples obtained serially ofr 24 hours were compared to microscopic changes in hearts from the same animals examined 48 hours after occlusion. Twelve of the 34 dogs died within two hours after coronary occlusion. Among the surviving 22 dogs, one failed to exhibit gross of electrocardiographic evidence of ischemia and was therefore excluded. Twelve had coronary occlusion maintained for 30 minutes or longer and in 11 of these peak plasma MB CPK activity exceeded thenormal range (mean +/- 2 SD) and baseline values by at least 100%. Necrosis was present in the hearts from each manifested by nuclear pyknosis, eosinophilia, shrinkage of cytoplasm, and leukocytic infiltration. In the remaining nine dogs with occlusion for less than 30 minutes, peak plasma MB CPK activity was not elevated and necrosis was not detected. The close concordance between plasma MB CPK elevations and myocardial necrosis was significant (chi2 = 14.5, P less than 0.001), and thus, increased plasma MB CPK activity reflected irreversible myocardial ischemic injury.


Cellular protection during myocardial ischemia: the development and characterization of a procedure for the induction of reversible ischemic arrest. An isolated perfused working rat heart model was used to investigate the extent to which various protective agents, used either singly or in combination, were able to increase the resistance of the heart to periods of transient ischemia. The aim of the studies was to develop a solution which, if infused into the coronary vessels just prior to the onset of ischemia, would rapidly induce arrest and would also counteract several of the deleterious cellular changes known to occur during myocardial ischemia. Agents with induce cardiac arrest, modify cellular ion loss, affect substrate utilization, energy production and energy stores, affect coronary vessel diameter and cell swelling, prevent dysrhythmias, and affect metabolic rate were investigated. The additive effects of these agents were evaluated. An aqueous solution was formulated which contained high concentrations of potassium and magnesium, in combination with adenosine triphosphate, creatine phosphate and procaine. This solution increased the recovery of the ischemic (37 degrees C for 30 min) rat heart from 0% to 93%. The safe period of ischemia could be further increased by the use of hypothermia.


Acute myocardial infarction with normal coronary arteries: a possible manifestation of the billowing mitral leaflet syndrome. The findings in four young patients with the billowing mitral leaflet syndrome who presented with evidence of acute myocardial infarction are reported. Because technically adequate coronary arteriograms demonstrated patent vessels and the electrocardiograms initially showed pronounced elevation of the ST segments as occurs in Prinzmetal's angina, it is postulated that spasm of normal coronary arteries was the operative factor. Scrutiny of those cases of clinically apparent ischemic heart disease with normal coronary angiograms is suggested to establish whether there is in fact a causal relationship with the billowing mitral leaflet syndrome.


The clinical significance of exercise-induced ST-segment elevation. The significance of exercise-induced ST-segment elevation remains unsettled. We reviewed the treadmill tests of 840 consecutive patients and exercise-induced ST-segment elevation was noted in 29 (3.5%). Only eight of these (28%) stopped because of angina. Anterior myocardial infarction (AMI) was found on the resting electrocardiogram in 25 (85%). Angiographic studies performed on 21 showed critical lesions of the left anterior descending (LAD) in 19 (90%) and left ventricular aneurysm in 18 (86%). When all the patiens who had AMI or critical LAD obstruction during the study period were reviewed, only 22% and 18% respectively showed exercise-induced ST-segment elevation, while 64% of the cases with left ventricular aneurysm displayed this phenomenon. Thus, exercise-induced ST elevation seems to reflect the presence of severe coronary artery disease most commonly with an associated left ventricular aneurysm and may relate more to the abnormal wall motion than to the myocardial ischemia per se.


Two to three years of failure-free testing of a rechargeable pacemaker in experimental complete heart block. Six hermetically sealed single cell rechargeable mercury-zinc pacemakers (B.T.) that will run continuously for over 4 years between rechargings have paced dogs with complete heart block for from 2 to 3 years. To maintain full cell capacity (over 1,000 mA hours) requires recharging for from 2-3 min/day to 60 to 80 hr once every 4 years, with any variation between these extremes being acceptable. Six realtime bench tests continue after over 7 years and accelerated tests have simulated a minimum of 50 years continuous pacing. Battery voltage is assessed by direct telemetry, eliminating the risk of patient intrinsic rhythm-pacemaker competition which is present with all current indirect (stimulation rate change) battery assessment techniques. The B.T. is an excellent 4-5 year primary pacemaker, fully rechargeable after several 4 year periods of battery rundown. A clinical test series has been initiated.


Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia. The short half-life positron emitter 13N, as labeled ammonia (13NH4+), was evaluated as a myocardial imaging agent. Regional myocardial uptake of 13NH4 correlated with the distribution of labeled microspheres in experimental myocardial infarction. Using intravenous 13NH4+, myocardial scintigraphy was performed in 85 cardiac patients and 27 normal subjects. Ninety-five scintigrams were suitable for analysis. Eighteen of 24 normal subjects had homogeneous myocardial images; six had inhomogeneous images attributable to early technical problems. Perfusion defects were observed in the scintigrams of 82% (57/65) of patients with coronary artery disease, being most common in patients with myocardial infarction (27/28). Six sequential studies showed changes in perfusion consistent with the clinical course of each patient. Scintigraphic abnormalities were also observed in 4/6 patients with valvular heart disease. 13NH4+ myocardial scintigraphy is a valid and sensitive method of assessing regional myocardial perfusion and is especially useful for sequential imaging at short intervals.