George G. Rowe

Blood flow reductions in stenosed canine coronary arteries: vasospasm or platelet aggregation?

In 67 dogs with a 60-80% coronary stenosis produced by an external constricting plastic ring, blood flow measured with an electromagnetic flowmeter showed cyclical flow reductions of varying magnitude and duration, and then an abrupt return to control flow. In 45 dogs, heparin did not prevent these flow reductions, but ibuprofen (Motrin) or indomethacin abolished them. With incremental doses of each of these drugs, the cyclical flow reductions and the platelet function in vitro were diminished proportionately. In 10 more dogs, during low flow, pinching or poking the narrowed vessel suddenly restored normal flow. Topical application of papaverine and nitroglycerin proximal to the stenosis did not abolish the cyclic flow reduction, although a transient fall in systemic pressure indicated that they had been absorbed. Seven dogs had the constricting cylinder and flow probe chronically implanted for 4-6 weeks. A single oral dose of aspirin, 20 mg/kg, abolished their cyclic flow reductions for 2-4 days. In five dogs with 70% stenosis in the circumflex coronary artery, coronary arteriography was performed before coronary flow reduction and when coronary blood flow was low. This showed that there was a considerable additional reduction in the size of the mechanically constricted lumen during spontaneous flow reduction. In one dog, a nonopacified mass was dislodged from the area of constriction in 67 msec and this restored the lumen to its control diameter. Similar rapid clearing was filmed in two more dogs. In no case was vasospasm observed. These results suggest that obstruction from platelets aggregated in the narrowed lumen caused the cyclic flow reductions.

A Study of Hemodynamics and Coronary Blood Flow in Man with Coronary Artery Disease

Coronary blood flow was measured by the nitrous oxide method, and cardiac output was measured by the Fick principle, in a series of 31 human subjects with the clinical diagnosis of angina pectoris. Coronary arteriography was carried out on the same subjects as a part of the same procedure, and the extent and severity of the coronary artery lesions was determined. A numerical value was assigned to the severity of the coronary artery disease, an attempt was made to correlate the severity of coronary artery disease with the measured coronary blood flow and with various hemodynamic parameters which traditionally describe the systemic and pulmonary circulation. There was no correlation between any of the parameters measured and the severity of coronary artery disease demonstrated by angiography. It is concluded, therefore, that the nitrous oxide method for measuring coronary blood flow is not helpful in separating subjects with normal coronary arteries from those with coronary artery disease, nor are resting hemodynamic observations helpful.Maximum flow through the coronary arteries of the dog heart was measured by postmortem perfusion. This flow rate is sufficient to provide a considerable factor of safety as far as constriction of the major coronary arteries is concerned. If these data are extrapolated to the coronary vessels of man, it would seem that a very large “safety factor” exists, and this may explain why severe coronary disease is not revealed by studies of coronary blood flow.

Subepicardial vasodilator reserve in the presence of critical coronary stenosis in dogs

Abstract Critical coronary stenosis is the term used to describe obstruction that eliminates reactive hyperemia presumably because downstream arterioles have dilated maximally to compensate for a proximal stenosis. However, evidence of distal vasomotor capacity exists despite the presence of severe constriction. Coronary blood flow in the left circumflex artery and blood pressure in the aorta and distal circumflex artery were studied in six open chest, anesthetized dogs. The circumflex artery was obstructed sufficiently to eliminate 95 to 98 percent of reactive hyperemia, but resting coronary blood flow was not reduced. The regional distribution of myocardial blood flow was studied with tracer microspheres (diameter 15 μm) before and after intracoronary injection of adenosine (5 μmoles) and after the release of a 15 to 20 second occlusion. The subendocardial to subepicardial ratio of flow in the obstructed bed was not changed by the stenosis (ratio 1.23 ± 0.10 [mean ± standard error of the mean] versus 1.28 ± 0.07, difference not significant). Administration of adenosine decreased subendocardial flow from 0.95 ± 0.07 to 0.73 ± 0.08 ml/min per g (p

Systemic and coronary hemodynamic effects of sodium nitroprusside

Treatment for hypertensive crises with sodium nitroprusside was reported1-4 many years ago and it was shown to be rapidly effective in controlling various hypertensive states including the hypertension induced by pheochromocytoma after phentolamine was no longer effective.5 Its systemic hemodynamic effects were studied in man and its hypotensive action was con6rmed.6 However, it was not used widely at least partly because of its toxicity. 7-g There has been wide recent clinical interestlO-l3 in the use of the drug, however, and its hemodynamic effects have been restudied in subjects with coronary artery disease or cardiomyopathy14 and its renal effects were studied in hypertensive subjects15 and in the dog.16The data obtained previously in dogs’ and rnan6,14,15 did not include observations concerning coronary blood flow and myocardial metabolism. This seems of critical importance in hypotensive subjects. Therefore the present study was done.

Epinephrine potentiation of in viw stimuli reverses aspirin inhibition of platelet thrombos formation in stenosed canine coronary arteries

Abstract In 18 anesthetized dogs with a 70% mechanically produced coronary artery stenosis, blood flow measured with an electromagnetic flowmeter showed cyclical reductions in flow due to periodic acute platelet thrombus formation. These were abolished in eight of nine dogs with 2.5 mg/kg of aspirin given intravenously and in nine of nine dogs with 5 ug/kg of aspirin. However in 14 of 18 dogs the cyclical flow reductions were temporarily renewed with the infusion of epinephrine 0.4 ug/kg/min. Human platelets inhibited with aspirin can be reactivated with physiologic amounts of epinephrine. We postulate that in patients with atherosclerotic stenotic lesions the use of aspirin to inhibit arterial thrombus formation may be less effective when they have elevated catecholamines.

Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation

1. Recent experimental data support the view that prostaglandins might be involved in autoregulation of coronary blood flow. Since indomethacin blocks prostaglandin synthesis, the present study was performed to determine whether indomethacin also inhibits coronary vasodilatation induced by hypoxia.

Tricuspid Insufficiency A Study of Hemodynamics and Pathogenesis

The clinical diagnosis of the presence and severity of tricuspid insufficiency is difficult and is complicated by the transient nature of this abnormality as well as its usual occurrence in subjects with other valve disease. This paper presents correlative hemodynamic data from 100 consecutive catheterized patients with valvular heart disease in 90 of whom the presence of tricuspid insufficiency was sought by the indicator-dilution technic. Tricuspid regurgitation was present in 28 of the 90 patients. Subjects were grouped into 20 controls without tricuspid insufficiency and those with mild, moderate, and severe tricuspid insufficiency. The hemodynamics of these groups were compared by the analysis of variance to determine which parameters relate most closely to tricuspid insufficiency. The results are interpreted to confirm that tricuspid insufficiency results from those factors which overdistend the right side of the heart, and by permitting blood to escape retrograde from the right ventricle serves as a safety valve preventing progressive overload of the pulmonary circulation.

Cor triatriatum dexter: Persistent right sinus venosus valve☆

Abstract The usual causes of a large right to left shunt at the atrial level are tricuspid or pulmonary atresia, severe pulmonary stenosis, Ebsteins anomaly or a large atrial septal defect with pulmonary hypertension. We have recently evaluated a patient with a large right atrial membrane which subdivided the right atrium into 2 chambers with the venae cavae and foramen ovale on one side of the web and the coronary sinus and a small tricuspid valve on the other. The presence of this membrane was demonstrated preoperatively by cineangiograms, and it was successfully removed at operation. This unusual entity, cor triatriatum dexter, is discussed and the literature reviewed.

Systemic and Coronary Hemodynamic Effects of Vasopressin

In the intact, anesthetized dog, an intravenous infusion of 0.02 U/kg body weight/min of Vasopressin increased the total peripheral, pulmonary, and coronary vascular resistance and decreased coronary blood flow and cardiac output There was a slight increase in systemic arterial blood pressure, A decrease occurred in total body and myocardial oxygen consumption and carbon dioxide production. There was on increase in systemic arterial lactate levels. Decreases in the arterial and venous blood oxygen content and pH suggested a decrease in tissue oxygenation, however, no total body “excess lactate” was produced. Paradoxically, calculated myocardial “excess lactate” was positive during both the control and Vasopressin infusion periods. Although the coronary sinus oxygen content decreased and the arterial-coronary sinus oxygen difference increased, lactate continued to be extracted by the myocardium suggesting the maintenance of aerobic myocardial metabolism.

Effect of Propranolol on Systemic and Coronary Hemodynamics at Rest and during Simulated Exercise

The systemic and coronary hemodynamic effects of relatively large doses of propranolol have been studied following its infusion into intact anesthetized dogs at rest and during simulated exercise. At rest, the administration of propranolol was associated with decreased cardiac output and ventricular work and increased peripheral, pulmonary, and coronary vascular resistances. Coronary blood flow and coronary sinus oxygen content decreased while myocardial oxygen consumption and the index of cardiac efficiency were unchanged. The usual hemodynamic response to mild exercise was obtained, with increased cardiac output, cardiac work, body oxygen consumption, and a modest but insignificant increase in coronary blood flow. When propranolol was given and the same exercise continued, body oxygen consumption, cardiac output, and left ventricular work significantly decreased. Insignificant decreases occurred in coronary blood flow, left ventricular oxygen usage, and coronary sinus oxygen content. The present observations are consistent with the thesis that beta-adrenergic blockade induced by propranolol decreases cardiac work at rest and reduces the cardiovascular response to exercise.