Donald E. Gregg

Effect of Exercise on Cardiac Output, Left Coronary Flow and Myocardial Metabolism in the Unanesthetized Dog

Cardiac output, left coronary artery flow, central aortic blood pressure and myocardial metabolism have been studied in the intact unanesthetized dog during exercise. Cardiac output and left coronary artery flow increase 350 to 400% during moderately severe exercise. The primary mechanical determinant of this increase appears to be cardio-acceleration; the stroke volume and stroke coronary flow contribution is relatively mild. Myocardial oxygen usage increases 300% or more with only a small elevation of the percentage of extraction of oxygen. The large increase of coronary flow in the dog and the significant elevation in hematocrit supply the extra oxygen.

Effect of Cardiac Contraction on Coronary Blood Flow

In the experimental animal the basic and controversial problem was studied of the influence of cardiac contraction on coronary blood flow. Normally beating hearts were perfused at a constant pressure, and coronary inflow and outflow were determined. In order to assess the role of systole, prolonged periods of ventricular asystole and fibrillation were induced and observations were made of the changes in coronary flow. With the cessation of cardiac contraction blood flow in the coronary arteries and coronary sinus rose appreciably. The results of these studies support the concept that contraction of the heart muscle, by compression of the myocardial vascular bed, behaves as a throttling mechanism and impedes coronary flow. The method employed permits a separation and quantitation of the effects on coronary flow resulting from cardiac contraction and the vasomotor state of the coronary vessels.

Phasic right coronary artery blood flow in conscious dogs with normal and elevated right ventricular pressures.

We studied phasic right coronary blood flow in well trained normal dogs and dogs with pulmonic stenosis. We installed electromagnetic flow transducers and pressure tubes under anesthesia to monitor right coronary blood flow, cardiac output, central aortic blood pressure, and right ventricular pressure. In norraotensive dogs, systolic flow amplitude equaled early diastolic flow levels. The ratio of systolic to diastolic flow at rest was substantially greater in the right coronary bed (36 ± 1.3%) than in tbe left circumflex bed (13 ± 3.6%). Right diastolic flow runoff, including the cove late in diastole, resembled left circumflex runoff. Blood flow to the normotensive right (37 ± 1.1 ml/min 100-1 g) and the left (35 ± 1.0 ml/mln-1 g) ventricular myocardium indicated equal perfusion of both cardiac walls. Throttling of systolic flow was related directly to the right ventricular systolic pressure level in the dogs with pulmonic stenosis. Retrograde systolic flow occurred in severe right ventricular hypertension. The late diastolic runoff pattern in dogs with pulmonic stenosis appeared the same as for the normotensive dogs. We obtained systolic to diastolic flow ratios of 1/3 the value of normotensive hearts in high and severe pulmonic hypertension. Electrocardiograms and studies of pathology suggested restricted blood flow to the inner layers of the right myocardium in the dogs with severe and high right ventricular hypertension. Normotensive and hypertensive peak hyperemic flow responses were similar, except for an increased magnitude of diastolic flow, with proportionately less systolic flow in hypertensive states.

Systemic and Coronary Energetics in the Resting Unanesthetized Dog

This report is an initial attempt to study the coronary circulation in the chronic unanesthetized dog. A standardized preparation has been developed in which phasic aortic pressure and flow, phasic left coronary inflow, and myocardial metabolism have been studied for many weeks in the unanesthetized dog under resting conditions. The flow patterns in the main left coronary artery and in its major branches are very similar. In the resting dog, the left coronary inflow during systole is 7 to 45% of that during diastole. We believe that much of this flow into the epicardial arteries penetrates into the myocardium. Stroke coronary flow can change considerably without significant alterations of blood pressure and heart rate. Despite this, the coronary flow values (37 to 58 cc) and oxygen usage values (4.4 cc to 8.6 cc) per 100 grams left ventricle per minute are low. Since, however, these measurements can vary considerably not only in different dogs but also in the same dog on the same day, and from day to day, it is suggested that these animals were in a semiresting state and probably not in a basal state.

Oxygen Uptake of the Nonworking Left Ventricle

Comparisons have been made in the open chest dog of the oxygen usage of the left ventricle whose external work has been reduced to zero by 4 different procedures. The average oxygen usage of the left myocardium/100 Gm./min. is about 2.0 cc. in complete arrest with vagal stimulation or with intracoronary potassium injection; 3.8 cc. in fibrillation; and 3.4 cc. in the empty but beating heart. The oxygen value in the arrested heart approximates 27 per cent of that in the control state and the uptake during vagal stoppage varies directly with the control metabolic level. In the fibrillating ventricle the higher values are related to the intensity of fibrillatory movements, and in the empty beating heart to the control metabolic rate and to the frequency of the heart beat. The experiments with vagal arrest also permit estimation of the oxygen debt of the myocardium.

Adrenergic Receptor Activity in the Coronary Arteries of the Unanesthetized Dog

Both α- (vasoconstrictor) and β- (vasodilator) receptor activity was demonstrated in the coronary arteries of the unanesthetized dog independent of adrenergic receptors in the myocardium. In the β-receptor blocked animal, α-adrenergic receptor activity was demonstrated after intravenous and intracoronary injections of epinephrine and norepinephrine by the occurrence of coronary vasoconstriction which could be eliminated by blocking α-adrenergic receptors as well. Coronary vasoconstriction was also seen prior to β-receptor blockade after intravenous phenylephrine and, on occasion, after intracoronary injections of norepinephrine. β-adrenergic receptor activity was demonstrated in several instances after intravenous or intracoronary injections of catecholamines by an initial vasodilatation which could be eliminated by β-adrenergic receptor blockade and which occurred before there was any change in myocardial or systemic hemodynamics. The role of this independent adrenergic receptor activity in the control of the coronary circulation remains to be determined.

Flow in the Major Branches of the Left Coronary Artery during Experimental Coronary Insufficiency in the Unanesthetized Dog

The dynamic changes in the coronary circulation and the response to drugs were studied following experimentally induced coronary insufficiency. Flow measurements were made in the left circumflex and descending branches of the coronary artery, and in the ascending aorta; pressures were measured in the ascending aorta and the left ventricle. As the left circumflex coronary artery branch was gradually constricted, reactive hyperemia following a 10-second occlusion of that vessel decreased. When the Degrees of constriction became such that the control resting flow began to fall, there was no reactive hyperemia, and the contractility index of the heart decreased. Within less than 24 hours, flow in the descending branch of the left coronary artery rose, and the cardiac contractility index returned to control; peak flow rate in the descending branch during reactive hyperemia after a 10-second occlusion also increased. The response to isoproterenol, nitroglycerin, and dipyridamole was similar in direction before and after the partial reduction of flow in the left circumflex coronary artery branch. The response was less in the coronary vessel with partial occlusion; in the unimpeded descending coronary artery branch, the response increased progressively. These results are consistent with the development of collateral vessels.

Some Determinants of Coronary Collateral Blood Flow in the Open-Chest Dog

Dynamics of the coronary collateral circulation have been investigated by means of the retrograde flow technic. A principal determinant of retrograde flow appears to be the perfusion pressure irrespective of the rate of coronary inflow. Nitroglycerine, histamine and norepinephrine failed to augment retrograde flow. Reactive hyperemia and temporary myocardial ischemia resulted in a reduction of retrograde flow which could be due to active vasoconstriction or to myocardial stretching. Changes in heart rate and the onset of ventricular fibrillation did not alter retrograde flow, but low blood viscosity increased it.

Day-to-Day Changes in Coronary Hemodynamics Secondary to Constriction of Circumflex Branch of Left Coronary Artery in Conscious Dogs

The studies were carried out in four dogs. The effects of applying ameroid constrictors to the circumflex branch were observed on the circumflex blood flow, circumflex and peripheral circumflex pressures, circumflex reactive hyperemia and aortic-circumflex pressure difference. Recordings were successfully made for periods of 16 to 64 days. During this time the circumflex branch became completely occluded in three of the dogs. The circumflex blood flow remained in the normal range until reactive hyperemia (following a 10- to 12-second occlusion of the circumflex branch) almost disappeared; the flow then decreased to zero in 5 to 10 days. Although there was some rise in mean peripheral circumflex pressure and aortic-circumflex pressure difference before circumflex blood flow decreased, the major rise in these variables occurred only when flow and reactive hyperemia became markedly decreased. The maximum rate of rise of mean peripheral circumflex pressure varied from 6 to 15 mm Hg/24 hours. The experiments indicate that a severe degree of coronary insufficiency precedes a rise in mean peripheral circumflex pressure to 60 to 70 mm Hg. We interpret such increments in mean peripheral circumflex pressure to mean that large collaterals must be open; the studies with injection of Schlesinger mass confirmed this interpretation.

Coronary Inflow and Oxygen Usage Following Cardiac Sympathetic Nerve Stimulation in Unanesthetized Dogs

The effects of cardiac sympathetic nerve stimulation on coronary inflow were studied in previously operated conscious dogs, using electromagnetic flowmeters. Stimulation caused an increase of coronary inflow which was due mainly to an augmentation of flow during diastole. In systole, inflow changes were smaller and variable according to the strength of stimulation. The data presented indicate that an arteriolar dilatation may play a role in augmenting coronary inflow. In several instances, the increase of coronary inflow was preceded by a phase of reduction which suggested the possibility of coronary vasoconstriction as a primary direct effect of cardiac sympathetic activation.