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Biomedical subjects

M L Marcus

Publications and source records attributed to M L Marcus.

At least 163 records · Page 9Linked to original sources
PubMed1981

Chronic progressive pressure overload of the cat right ventricle.

When an abrupt, fixed increase in afterload induces hypertrophy, the myocardium exhibits normal pump function in vivo, depressed muscle function in vitro, and paradoxically increased oxygen consumption. Such abnormalities may be either a transient response to a reversible myocardial injury or instead may be a persistent characteristic of hypertrophy contributing to eventual heart failure. To distinguish between these alternatives, we developed a model of chronic progressive pressure overload. Kittens had either a sham operation or pulmonary banding for 25 (group I) or 60 (group II) weeks. Banding produced a gradually increasing pressure overload with growth, maximum at 16 weeks after operation. The ratio of right ventricular to body weight increase from 0.54 +/- 0.03 to 0.82 +/0.04 g/kg (P less than 0.01) in group I and from 0.50 +/- 0.03 to 0.72 +/- 0.03 (P less than 0.01) in group II. In vivo right ventricular pump function (cardiac output and ejection fraction) was normal in both groups. In vitro contractile function and metabolism were measured in papillary muscles from the same right ventricles. Both experimental groups showed marked contractile abnormalities: preloaded shortening velocity was reduced from 0.80 +/- 0.05 to 0.53 +/- 0.05 muscle length/sec (P less than 0.01) in group I and from 0.84 +/- 0.04 to 0.60 +/- 0.06 (P less than ).01) in group II. Maximum isometric active tension was reduced from 60 +/- 7 to 35 +/- 5 mN/mm2 (P less than 0.01) in group I and from 56 +/- 5 to 27 +/- 4 (P less than 0.01) in group II. Metabolism was normal in both experimental groups. Thus, under conditions relevant to the study of clinical cardiac hypertrophy that are unlikely to cause acute injury, hypertrophy produces persistently abnormal intrinsic contractile function

Animals↗
PubMed1981

Hyperemia of the aortic wall in atherosclerotic monkeys.

The aortic wall is nourished by diffusion from the aortic lumen and from vasa vasorum in the adventitia and outer layers of media. Intimal proliferation in atherosclerosis might be expected to reduce the effectiveness of diffusion from the lumen and increase dependence on nourishment by vasa. This study was performed to determine whether there is increased perfusion of the aortic wall by vasa vasorum in atherosclerosis. We used microspheres to measure flow through vasa in normal and atherosclerotic cynomolgus monkeys. Blood flow to inner layers of the thoracic and abdominal aorta was less than 1 ml/min X 100 g in normal monkeys, and there was a minimal increase in atherosclerotic monkeys. Flow to the outer layers of the thoracic and abdominal aorta was 1.3 +/- 0.9 and 2.2 +/- 0.8 ml/min per 100 g in normal monkeys. Flow to outer layers of the thoracic and abdominal aorta was increased in atherosclerotic monkeys to 17 +/- 8.9 and 31 +/- 12 ml/min per 100 g (P less than 0.05 vs. normal). Thus there is increased perfusion of the atherosclerotic aorta, particularly in the outer layers. During maximal vasodilation induced by infusion of adenosine, flow through vasa was 3- to 8-fold greater in atherosclerotic than in normal monkeys. This finding suggests that proliferation of new vessels, rather than dilation of existing vessels, accounts for the increase in blood flow through vasa. We speculate that hyperemia of the aortic wall in atherosclerosis may be in part a compensatory response to increased oxygen requirements and possibly to ischemia produced by intimal proliferation and a resulting increase in diffusion distance.

Adenosine↗
PubMed1981

Liposome concentration in canine ischemic myocardium and depolarized myocardial cells.

To determine whether liposomes (microscopic phospholipid vesicles) may be useful in delivering drugs to a region of myocardial ischemia, we studied the concentration of positively charged and neutral liposomes containing 131I-albumin and horseradish peroxidase in ischemic myocardium of 20 dogs during the first 4 hours of experimental myocardial infarction. We studied the interaction of liposomes containing fluorescent dyes and horseradish peroxidase with isolated contracting cardiac myocytes. We found that positively charged and neutral liposomes accumulated in poorly perfused myocardium and that positively charged liposomes accumulated in the ischemic region to a greater extent than neutral liposomes [138 +/- 21 vs. 81 +/- 9% (mean +/- SE) of the concentration of liposomes in uninvolved myocardium]. Electron microscopic examination of this myocardium showed liposome contents to be located in the vascular space, in endothelial cells, and in ischemic myocytes. We found high potassium environment and that liposomal contents were scattered throughout the interior of the cells in the electron micrographs of some of the isolated myocytes. Anoxia alone for 20-30 minutes did not modify the liposome-isolated myocyte interaction or cause depolarization of the cells. We conclude that liposomes may be useful as drug carriers to depolarized ischemic myocardium, although significant uptake by normal myocardial cells cannot be expected with lecithin, cholesterol, and octadecylamine liposomes we used.

Animals↗
PubMed1981

Methods for measurement of cerebral blood flow.

Difficulties in measuring total and regional cerebral flow have hindered advances in knowledge concerning the regulation of the cerebral circulation. Now, however, we can accurately measure total and regional cerebral blood flow with the labeled microsphere method. With this method, flow to cerebral and non-cerebral tissues in the head can be completely separated, and by using microspheres labeled with different radionuclides, six measurements can be obtained in each experiment. A disadvantage of the microsphere method is that flow is not monitored continuously. Therefore, transient changes in flow (less than 20 seconds) cannot be measured accurately, and it is difficult to determine the time course of changes in cerebral blood flow in response to a given stimulus. A new method, simultaneous measurements of velocity and diameter in a pial artery, complements the microsphere approach. With this new method, nearly continuous, accurate measurements of cerebral blood flow are obtainable. Now that several methods for measuring cerebral blood flow are available and appear to be valid, knowledge concerning the regulation of cerebral blood flow should advance more rapidly.

Animals↗
PubMed1981

Neural effects on cerebral vessels: alteration of pressure-flow relationship.

Cerebral vessels are well innervated by adrenergic and cholinergic fibers. Effects of sympathetic stimulation on cerebral blood flow (CBF) are controversial, but we have concluded that, during normotension and hypotension, sympathetic nerves have little effect on CBF. During acute hypertension, however, sympathetic nerves may have important effects of CBF. Sympathetic stimulation attenuates the passive increase in CBF that occurs during severe steady-state hypertension and after a sudden, modest increase in pressure. Disruption of the blood-brain barrier, which occurs during severe hypertension, also is minimized by sympathetic stimulation. Thus, the concept has emerged that, in contrast to minimal effects of sympathetic nerves under most conditions, sympathetic stimulation may have important protective effects during hypertension. The role of cholinergic nerves in regulation of CBF has not yet been clarified.

Acetylcholine↗
PubMed1980

Comparative effects of catecholamines in cardiac tamponade: experimental and clinical studies.

In experimental cardiac tamponade, catecholamines improve hemodynamic variables. To determine whether hemodynamic changes result in increased blood flow to critical organs, tamponade was produced in nine spontaneously breathing, anesthetized dogs. Infusion of dopamine, isoproterenol or norepinephrine doubled cardiac output, but only norepinephrine increased mean arterial pressure. All catecholamines increased blood flow to the myocardium, but not to the brain or kidney. Isoproterenol caused a significant decrease in the endocardial/epicardial blood flow ratio, which was shown to be due to tachycardia. To determine whether catecholamines increase cardiac output and mean arterial pressure in patients with tamponade, eight patients with tamponade due to neoplasms were studied before therapeutic pericardiocentesis. Cardiac output increased only 50 percent with dopamine and isoproterenol and not at all with norepinephrine. Cardiac filling pressure did not decrease with isoproterenol or dopamine, as in experimental tamponade. Only norepinephrine increased mean arterial pressure. Thus, although catecholamines improve hemodynamics in experimental tamponade, the heart is the only critical organ to which blood flow is improved. The hemodynamic benefits of catecholamine administration to patients may be more limited than previous experimental studies have suggested.

Animals↗
PubMed1980

Inhibition of adrenergic neurotransmission in ischaemic regions of the canine left ventricle.

To test hypothesis that adrenergic neurotransmission is impaired in acute myocardial ischaemia, we studied contractile function of normal and ischaemic myocardium after coronary artery occlusion. For each area we compared the contractile response to left sympathetic nerve stimulation (LSS) with the response to exogenous noradrenaline (NA). Contractile response was measured with intramyocardial sonomicrometers. LSS increased aortic pressure and heart rate. NA was infused to achieve an aortic pressure equivalent to LSS and simultaneous atrial pacing matched the heart rate during LSS. In normal zones both interventions produced increased shortening equivalently. In ischaemic zones systolic expansion was unchanged during LSS, while NA improved contractile function of the same zones by decreasing systolic expansion. These responses occurred during ischaemia produced by either anterior or posterior descending coronary occlusion. Changes in regional blood flow, measured by 8 microns radiolabelled microspheres, could not account for the difference between the ischaemic regional response to LSS or NA. We conclude that acute regional ischaemia impairs adrenergic nerve transmission.

Adrenergic Fibers↗
PubMed1980

Effect of acetylcholine and vasoactive intestinal peptide on cerebral blood flow.

These experiments were performed to determine whether the neurotransmitters acetylcholine (ACh) and vasoactive intestinal peptide (VIP) increase cerebral blood flow (CBF). In anesthetized dogs, infusion of very large doses of ACh (500 microgram/min) into the carotid artery increased CBF (measured with microspheres) 50%. Anatomical limitations prevented adequate testing of cerebrovascular responses in dogs. In anesthetized rabbits, infusion of ACh (10 microgram/min) into the carotid artery produced a twofold increase in CBF. Vessels in gray matter were more responsive than vessels in white matter. ACh did not alter cerebral oxygen consumption, which indicates that the dilator effect of the drug is not an indirect effect mediated through an increase in metabolism. The vasodilator response to ACh was attenuated by atropine (1 mg iv). Intracarotid infusion of VIP in rabbits increased blood flow to cerebral gray matter: infusion of VIP (10 microgram/min) incresed flow 33%. We conclude that 1) cerebral vasodilator responses to ACh and VIP are larger than previously recognized and 2) responses to these drugs occur primarily in cerebral gray matter. Because the neurotransmitters increase CBF significantly, these studies should encourage further studies concerning effects of cholinergic and peptidergic nerves on cerebral vessels.

Acetylcholine↗
PubMed1980

Myocardial infarction in dogs with chronic hypertension and left ventricular hypertrophy.

Chronic hypertension increases the risk of myocardial infarction and the morbidity and mortality associated with it. Although accelerated atherosclerosis is partially responsible, other abnormalities in the coronary circulation associated with hypertension, such as decreased coronary vascular capacity and capillary density, could also contribute. To evaluate the effects of these nonatherosclerotic abnormalities, we produced sudden coronary occlusion in nine chronically hypertensive dogs. The mean aortic pressure and left ventricular mass were about 50% greater in hypertensive dogs than in the nine controls. Before occlusion and 5 min and 49 h after occlusion, myocardial blood flow was measured with tracer microspheres. Also, the extent of infarction in selected myocardial segments was quantified histologically. We found that coronary occlusion reduced flows to a similar extent, and that, over a 48-h period, collateral flow increased to a similar extent in the two groups. In addition, the amount of necrosis associated with a given degree of ischemia was similar in the two groups. Although the extent of the left ventricle that became ischemic was greater in the hypertensive dogs (28 +/- 2 vs. 18 +/- 4%; P < 0.05), chronic hypertension and left ventricular hypertrophy did not limit the recruitment of collateral supply or increase the amount of necrosis associated with a given degree of ischemia.

Animals↗
PubMed1980

Regional distribution of cerebral blood flow during exercise in dogs.

This study was performed to determine whether exercise produces vasodilatation in regions of the brain that are associated with motor functions despite the associated vasoconstrictor effect of hypocapnia. Total and regional cerebral blood flow (CBF) were measured with microspheres in dogs during treadmill exercise of moderate intensity. Flow was also measured at rest after stimulation of ventilation with doxapram. During moderate exercise, total CBF was not changed significantly, but regional flow was increased in structures associated with motor-sensory control; blood flow to motor-sensory cortex, neocerebellar and paleocerebellar cortex, and spinal cord increased 30 +/- 7%, 39 +/- 8%, and 29 +/- 4%, respectively (P less than 0.05). After doxapram, which increased arterial blood pressure and decreased arterial PCO2 to levels similar to those during exercise, total CBF decreased and there was no redistribution of CBF. These results indicate that exercise in conscious dogs increases blood flow in regions of the brain associated with movement despite the associated vasoconstrictor stimulus of arterial hypocapnia. Thus, during exercise, local dilator influences that presumably result from increases in metabolism predominate over a potent constrictor stimulus in regulation of cerebral vascular resistance.

Animals↗
PubMed1980

Exercise capacity in patients with severe left ventricular dysfunction.

Normal or near-normal exercise capacity has been thought to reflect normal left ventricular function. Many compensatory mechanisms could preserve exercise capacity in patients with severe left ventricular dysfunction. We evaluated exercise capacity using a treadmill exercise test in 26 patients with severe left ventricular dysfunction defined by a left ventricular ejection fraction of 30% or less by isotope ventriculography. One half of the patients had normal exercise capacity and a normal cardiothoracic ratio on chest x-ray. This study indicates that traditional predictors of left ventricular function that have been widely used in clinical evaluation of the patients with cardiac disease (cardiothoracic ratio and exercise capacity) can be normal in a significant number of patients with severe left ventricular dysfunction. Thus, left ventricular function cannot be accurately estimated using these traditional predictors and should be assessed quantitatively. The isotope ventriculogram appears to be ideal for this purpose.

Adult↗