The effects of nitroglycerin on regional myocardial contractile dysfunction produced by treadmill exercise or isoprenaline stimulation in dogs

Abstract

To compare different methods of cardiac stress testing that are clinically applied in the management of coronary heart disease, 2 groups of dogs each were chronically instrumented and subjected to treadmill exercise or isoprenaline infusion in the presence of coronary stenosis. It was of interest to determine differences in haemodynamic and regional myocardial contractile parameters, the response to antianginal therapy (nitroglycerin 15μgkg−1 15min−1, i.v.), and, in particular, whether this response differed according to the mode of cardiac stimulation, i.e. treadmill exercise or isoprenaline infusion. After stenosis of the circumflex branch of the left coronary artery which affected resting myocardial function only minimally, treadmill exercise or isoprenaline infusion induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular end‐diastolic pressure and left ventricular dp/dtmax were registered and myocardial oxygen demand was calculated. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. Treadmill exercise led to an increase in systolic arterial and left ventricular end‐diastolic pressure. In contrast, isoprenaline‐induced stimulation led to a decrease in diastolic arterial and left ventricular end‐diastolic pressure. Regional contractile function in the critically underperfused area showed a deterioration during both modes of stress. Nitroglycerin completely abolished stress‐induced contractile dysfunction only in the group where treadmill exercise was employed for stimulation. The inability of nitroglycerin to prevent myocardial dysfunction in the isoprenaline group may be due to exhaustion of the arterial and/or venous vasodilator potency of nitroglycerin in the presence of adrenoceptor vasodilatation induced by isoprenaline. These findings indicate that clinical antianginal drug testing and the evaluation of the course of disease in patients with coronary heart disease may be highly dependent on the test method chosen.

Vasopeptidase Inhibition In A Canine Model Of Exercise‐Induced Left Ventricular Dysfunction

“…Direct actions on the coronary circulation include dilation of large and small intramural coronary arteries, collateral vessel dilation and replenishment of nitric oxide 30 . As is the case in humans, prior studies have demonstrated an unequivocal and beneficial effect with TNG in various canine models of demand ischaemia 27,28,31–34 . The lack of change in double product with TNG suggests that peak myocardial oxygen consumption remained unchanged while peak exercise capacity was increased by 16%, consistent with the known ability of TNG to reduce myocardial oxygen demand.…”

“…30 As is the case in humans, prior studies have demonstrated an unequivocal and beneficial effect with TNG in various canine models of demand ischaemia. 27,28,[31][32][33][34] The lack of change in double product with TNG suggests that peak myocardial oxygen consumption remained unchanged while peak exercise capacity was increased by 16%, consistent with the known ability of TNG to reduce myocardial oxygen demand. Increased exercise capacity was accompanied by increased ischaemic zone wall thickening throughout the exercise protocol, with a similar beneficial effect noted in the ischaemic zone ST segment.…”

“…Nitroglycerin is a well‐documented anti‐anginal agent that improves global and regional left ventricular function 27–29 and was chosen as a positive control for the present study. Mechanisms of action include reduction of myocardial oxygen demand secondary to venodilation and arterial–arteriolar dilation, leading to a reduction in ventricular wall stress.…”

Esmolol: effects on isoprenaline- and exercise-induced cardiovascular stimulation in conscious dogs

“…Additional chronotropic effects may be caused by reflex vagd withdrawal (Bunlop and Shanks 1968) and a concomitant sympathetic activation in response to the fdl in arterial blood pressure that is mediated by isoprenaline stimulation sf vascular /32-adrenoceptors. lsoprenaline reduces the end-diastolic segmental lengths in the left ventricular wall, which are a rough measure of the overall left ventricular volume (Schneider et al 1988). Therefore, it may be assumed that isoprendine in the present study also reduced the left ventricular volume, in addition to inducing the observed decrease in left ventricular enddiastolic pressure.…”