Effects of Catecholamines, Exercise, and Nitroglycerin on the Normal and Ischemic Myocardium in Conscious Dogs

Abstract

A B S T R A C T The effects of isoproterenol, norepinephrine, dobutamine, exercise, and nitroglycerin on left ventricular diameter, pressure, velocity of shortening, dP/dt, dP/dt/P, arterial pressure, left circumflex coronary blood flow, and coronary vascular resistance were examined in healthy conscious dogs with normal coronary perfusion and in the same animals after moderate global ischemia had been induced by partial occlusion of the left main coronary artery. In the normal nonischemic heart, all interventions improved left ventricular performance, as evidenced by increases in dP/ dt/P and velocity at the same or lower left ventricular end-diastolic diameter. Interventions, which in the normal heart caused large increases in heart rate and myocardial contractility, e.g. isoproterenol and exercise, or which decreased coronary perfusion pressure, e.g. nitroglycerin or isoproterenol, elicited paradoxical responses in moderate global ischemia, i.e., left ventricular enddiastolic diameter and pressure rose, and dP/dt/P and velocity fell substantially. On the other hand, norepinephrine, which increased coronary perfusion pressure along with myocardial contractility but did not increase heart rate, improved left ventricular function. Dobutamine, which did not alter heart rate or arterial pressure substantially while improving myocardial contractility, produced an intermediate response between that of norepinephrine and isoproterenol in the presence of moderate

Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.

“…To simulate this situation of regional ischemia, only one major coronary artery was occluded in the present study. Under these conditions, isoproterenol infusion improved overall cardiac performance, as measured by LV diameter, pressure, velocity, and dP/dt/P, to a degree intermediate between what was previously observed in normal, conscious dogs in the presence and absence of global myocardial ischemia (1). These techniques, however, do not accurately reflect the responses of the different zones of myocardium in the presence of regional ischemia.…”

“…In a previous study from this laboratory, the effects of isoproterenol were examined in conscious dogs in the presence and absence of marginal, global myocardial ischemia, induced by partial constriction of the left main coronary artery (1). Under these two circumstances, opposing reactions to the drug were observed.…”

“…(dP/dt/P). These techniques for evaluating the myocardial contractile state have been described in detail previously (1,3,(10)(11)(12). The effects of interventions on regional myocardial function were assessed by measurement of stroke shortening, velocity of segment shortening, and end-diastolic and end-systolic segment lengths.…”

“…When isoproterenol is administered in the presence of global myocardial ischemia, a situation in which the entire myocardium is perfused inadequately, a paradoxical effect occurs, i.e., myocardial function deteriorates rapidly (1,2). The effects of isoproterenol on myocardial function in the presence of regional ischemia, where the myocardium is perfused heterogeneously, are more complex.…”

Exercise-induced regional dysfunction with subcritical coronary stenosis.

“…3, 596-605, 1986. EXERCISE-INDUCED ischemia has been studied in detail experimentally with analyses of regional myocardial blood flow (MBF),'-s regional contraction, [4][5][6][7] and overall left ventricular function.5 [8][9] These data and other studies in resting conscious dogs'0-2 have established that regional contractile function is responsive to reductions in MBF, especially to the subendocardium. For example, in the presence of critical coronary stenosis (normal resting flow but lack of vasodilator reserve), subendocardial coronary flow drops 50% below the resting value during exercise, with an assoicated 70% decrease of systolic wall thickening below the resting value.…”