Comparative effects of nicardipine, a new calcium antagonist, on size of myocardial infarction after coronary artery occlusion in dogs.

Abstract

To examine whether nicardipine, a dihydropyridine derivative, limits size of myocardial infarction, and to compare the protective effects of nicardipine administered before and early and late after coronary artery occlusion, 99mTc-labeled albumin microspheres were injected into the left atrium during 5 min temporary coronary artery occlusion to determine the extent of the hypoperfused zone (the area at risk). The coronary arteries were then reperfused for 45 min before 6 hr permanent coronary artery occlusion. Fifteen minutes before permanent occlusion, dogs were randomly assigned to (1) a control group (n = 11), (2) a pretreatment group (n = 9), which received at this point 10 ,g/kg of nicardipine as a loading dose followed by a continuous infusion of 8 p.g/kg/hr for 6 hr, (3) an early treatment group (n = 9), in which nicardipine treatment was initiated 15 min after occlusion, or (4) a late treatment group (n = 8), in which nicardipine administration was delayed for 3 hr. Six hours after coronary artery occlusion, the hearts were excised and the left ventricle of each was cut into 3 mm thick slices and stained with triphenyltetrazolium chloride. The extent of myocardial necrosis was measured by planimetry of the unstained areas. Thereafter, the same slices were autoradiographed and the extent of the hypoperfused zone was measured by planimetry of the "cold spot." The extent of the hypoperfused zone was identical among the four groups. In the control group, the ratio of the extent of myocardial necrosis to the extent of the hypoperfused zone was 95.8 3.8% (mean SEM). However, it was significantly smaller in the pretreatment group (59.9 + 13.3%, p < .05) and the early treatment group (49.0 + 10.6%, p < .01) than in the control group. In the late treatment group, this value was not different from that in the control group (86.5 + 7.1%). There was a close inverse correlation between reduction of infarct size and the extent of the hypoperfused zone in the pretreatment and early treatment groups. Thus, nicardipine administered before or early after coronary artery occlusion limited infarct size by 37% to 49%, whereas when administration was delayed for 3 hr infarct size was not reduced. Furthermore, nicardipine had more striking effects on the ischemic myocardium of dogs with small hypoperfused zones than on that of dogs with large hypoperfused zones. Circulation 74, No. 2, 420-430, 1986. IN 1969

Does the Extent of the Zone at Risk after Coronary Artery Occlusion Influence the Percentage of the Zone that Evolves to Infarction?

“…To assess the hypoperfused zone of the myocardium after coronary artery occlusion, we employed the autoradiographic tech nique [2,3,14,15]. Using this method, we could assess the hypoperfused zone, taking into account both the reduction in coronary blood flow due to coronary occlusion itself and the coexisting collateral blood flow from the normal area to the one rendered hypo perfused, i.e.…”

“…Thus, in this study, a much greater percent age of the myocardium at risk evolved to infarction during coronary artery occlusion, as compared with those using the postmor tem intracoronary injection of dyes (60-79% of the risk zone) [4,6,8] or barium gels (32-52%) [5,7,11], Postmortem intracoronary injection of different-colored dyes or radio paque material defines the risk area as the anatomic region supplied by the occluded coronary artery, that is a baseline constant and determined by coronary anatomy. The 'physiologic' risk zone, defined as the area of moderate or severe ischemia based on a graded concentration of injected particles or radioisotope, can be altered by spontaneous or therapeutically induced changes in collat eral blood flow during an experiment [2,3,9,14,15,17], Cheung et al [18] evaluated a change in the extent of the hypoperfused zone in the course of acute myocardial in farction by double autoradiography, inject ing 99mTc-or 11'In-labeled albumin micro spheres into the left atrium 1 min and 6 h after coronary artery occlusion in the same dogs. They reported a 3% reduction of the extent of the hypoperfused zone during 6 h of permanent coronary artery occlusion in the untreated dogs (from 27.1 ± 4.5% of the left ventricle to 26.2 ± 4.7%), although the difference was not statistically significant.…”

“…The incidence of ventricular fibrillation in our model of myocardial infarction was 32 % [ 14,15]. Detailed methods have been published previously [3,14,15]. Briefly, 34 mongrel dogs of both sexes weigh ing 16-26 kg were anesthetized with thiamylal so dium (25 mg/kg), intubated and artificially ventilated with room air using a volume-limited respirator.…”

“…The dogs were then classified into two groups according to the extent of the hypoperfused zone: those with small (< 3 0 % of the left ventricle; n = 23) and large (> 30% of the left ventricle: n = 11) hypoperfused zones. A cutoff value of 30% of the left ventricle was chosen, because in our previous studies the extent of the hypoperfused zone has been shown to influence the occurrence of ventricular arrhyth mias and the effectiveness of an intervention to re duce infarct size (3,14]. Thus, more frequent ventric ular arrhythmias and a less beneficial effect of an intervention on the ischemic myocardium were ob served in dogs with hypoperfused zones of more than 30% of the left ventricle than in dogs with hypoper fused zones of less than 30% of the left ventricle.…”

“…We employed autoradiography to quantify the extent of the hypoperfused zone of the myocardium, i.e. the area at risk for infarction, after coronary artery occlu sion [2,3,14,15].…”