Effect of antianginal drugs on distribution of blood flow in the ischemic myocardium (Experimental study using cross-thermocouple)

Effect of antianginal drugs on the regional blood flow in the ischemic myocardium and systemic hemodynamics induced with coronary constriction was studied using twenty eight anesthetized open-chest dogs. The regional myocardial blood flow in the inner- (subendocardial) and outer- (subepicardial) layer of the left ventricular wall was continuously monitored by heated cross-thermocouples designed according to Grayson's heat exchange principle. The left circumflex branch of the coronary artery was gradually constricted by a screw type constrictor until myocardial reactive hyperemia following 15-second occlusion of the vessel nearly disappeared. Subsequently, the antianginal drug (nitroglycerin, 20μg/Kg; dipyridamole, 0.3mg/Kg, or prenylamine, 1.0mg/Kg) was administered intravenously. The results were as follows:(1) Almost no difference in the regional blood flow between the inner and outer-layer was present before coronary constriction. After coronary constriction, the flow through the inner-layer and the flow ratio of the inner to the outer-layer (I/O ratio) in the ischemic myocardium decreased and left ventricular end-diastolic pressure (LVEDP) was slightly elevated. (2) Nitroglycerin produced essentially no change in the flow through the inner-layer despite a concomitant drop in aortic blood pressure after an initial decrease, whereas it did a remarkable decrease in the flow through the outer-layer. Therefore, the I/O ratio in the ischemic myocardium was elevated significantly from 1 to 7.5 minutes after the administration. During this period aortic blood pressure gradually returned to the previous level and LVEDP was still lowered. (3) Dipyridamole produced a decrease in the flow through the inner-layer, while only minimal change was observed in the flow through the outer-layer. Consequently, the ratio in the ischemic myocardium was reduced significantly from 1 to 5 minutes after the injection when aortic blood pressure was lowered and LVEDP remained unchanged. (4) Prenylamine caused a more decreased flow through the inner-layer than the outer-layer. Hence, the ratio in the ischemic myocardium was reduced from 1 to 3 minutes after the injection when aortic blood pressure was lowered and LVEDP remained unchanged. As mentioned above, the non-uniform distribution of blood flow in the ischemic myocardium following coronary constriction was improved by nitroglycerin and further augmented by dipyridamole or prenylamine. The different effects of these antianginal drugs on the regional myocardial blood flow and its distribution in the ischemic myocadium might suggest that these drugs have different sites of the action on the coronary vascular bed and effects on the systemic hemodynamics, especially on the left ventricular preload.