Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons.

Abstract

Two groups of chronically instrumented, conscious baboons were studied. The effects of coronary artery occlusion for 3 hours and reperfusion for 1 week were examined on measurements of left ventricular function, ischemic-zone wall thickness, regional myocardial blood flow, arrhythmias, and extent of necrosis. The experimental group of animals (n = 7) was treated with the calcium channel blocker nisoldipine (0.1 /i,g/kg/min) from 1 hour after coronary occlusion to 3 hours after coronary reperfusion. The control group (u = 6) received the vehicle (n = 4) or saline (n = 2). The effects of coronary artery occlusion and reperfusion on arterial pressure, left ventricular systolic pressure, heart rate, and left ventricular dP/dt were similar in both groups. Systolic wall thickening was reversed to paradoxical wall thinning during occlusion in both groups, and there was no recovery to systolic wall thickening over the 1-week period in either group. There were differences in regional blood flow; during coronary artery occlusion, nisoldipine increased blood flow significantly in the endocardium and epicardium of nonischemic and ischemic zones. There was a major difference in the number of arrhythmic beats per minute on reperfusion; during reperfusion, the number of arrhythmias rose markedly in the vehicle-treated group but actually fell in the nisoldipine-treated group. The size of areas at risk, infarcts, infarcts related to the area at risk, and amount of total creatine kinase (CK) and MB-CK appearing in blood were not significantly different in the two groups. Thus, in the conscious baboon, nisoldipine administered 1 hour after coronary artery occlusion exerted a marked effect in diminishing reperfusion-induced arrhythmias and improved blood flow to the ischemic zone during occlusion but did not salvage ischemic tissue. {Circulation Research 1988;62:105-115) C oronary artery reperfusion, if initiated soon enough after coronary artery occlusion, can ameliorate the effects of myocardial ischemia. If full reperfusion occurs within 20 minutes of coronary occlusion, no permanent damage occurs.

Effects on infarct size of reperfusion and pretreatment with β-blockade and calcium antagonists

“…The lack of comparable effect with diltiazem (Fig. 9b) confrms the general impression emerging from the literature (22,52) on the role of classical calcium antagonists in infarct size reduction.…”

“…investigators using pressure injection of dye or barium gel appear to be obtaining larger border zones in which collateral flow is of great importance (2,27). Our impressions were completely confirmed by the recent paper of Vatner et al (52) in which both methods were used; the perfused mass from the dye injection method was systematically greater than the "mass of tissue at risk" determined by the microsphere method. The autoradiographic method confirms in a clear pictorial presentation that the border between the normal zone and the ischaemic "at risk" zone is indeed extremely sharp (10).…”

Effect of amlodipine on myocardial functional and metabolic recovery following coronary occlusion and reperfusion in dogs

“…Since infarct size was not measured in the present experiments, it is unknown as to the role the infarct size is playing in the effects observed following amlodipine. It would be expected that amlodipine would reduce the infarct size via increases in collateral blood flow, however, Vatner and coworkers [31] found that the infarct size in conscious baboons was not reduced by nisoldipine, in spite of a drug-induced increase in collateral flow.…”

Role of calcium ions in reperfusion arrhythmias: Relevance to pharmacologic intervention

“…for 3 hours thereafter, reduced the incidence of latephase ventricular arrhythmias; however, the nisoldipine increased ischemic blood flow [58].…”

“…Baboon heart in situ + Lubbe et al [73] Winslow et al [62] Sheehan and Epstein [74] Coker and Parratt [75] Weishaar and Bing [76] Tosaki et al [52] Winslow et al [62] Sheehan and Epstein [74] Winslow et al [62] Brooks et al [77] Naito et al [59] Vatner et al [58] aCoronary artery ligation followed by reperfusion.…”