The effects of nifedipine on acute experimental myocardial ischemia and infarction in dogs.

Abstract

SUMMARY We studied 25 anesthetized and thoracotamized dogs before and during 5 hours of acute regional myocardial ischemia. Krypton-81m ( 8Xm Kr) was infused constantly into the aortic sinuses. The myocardial equilibrium of this tracer was used to image and assess the distribution of regional myocardial perfusion using a gamma camera and digital computer. The epicardial ECG was recorded, S-T segment elevation and the loss of R and appearance of Q waves were measured, and the plasma activity of creatine kinase (CK) was determined in aortic and coronary venous blood throughout these experiments. Ten dogs underwent left anterior descending coronary artery (LAD) narrowing for 5 hours and received no drugs. Five dogs received nifedipine 13 fig/kg, and another five received 1.0 /ig/kg intravenously 30 minutes after LAD narrowing. Those dogs receiving nifedipine, 13 fig/kg, showed a 30% fall in aortic pressure, a 12% rise in heart rate, and an extension of regional ischemia. The ECG showed an extension of infarct size, and CK release into the coronary vein appeared earlier than in the controls. Dogs receiving nifedipine, 1 /ig/kg, showed a 12% fall in blood pressure, no rise in heart rate, an improvement in regional perfusion, and ECG signs that suggested limitation of infarct size. There also was delayed release of coronary venous CK. The effects of nifedipine on the natural history of regional myocardial perfusion, the electrocardiogram, and enzyme release from the heart were dose related and cannot be generalized. These observations warrant further clinical investigation to improve the use of this agent in man. Circ Res 44: 16-23, 1979 THE extent of ischemic myocardial damage during acute myocardial infarction is one of the important determinants of morbidity and mortality. Recent studies have encouraged a search for interventions that can affect the balance between energy supply and demand during acute infarction of the heart (Maroko et al., 1971; Braunwald andMaroko, 1974). Nifedipine (4-(2'-nitrophenyl)-2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester) has been shown to retard the transmembrane influx of calcium into ischemic myocardial cells, increase coronary blood flow, delay ischemic contracture, and preserve myocardial creatine kinase activity (Henry, 1975;Fleckenstein, 1975;Vater, 1975;Schmier et al., 1975). These combined pharmacological properties suggest that a favorable effect on acutely ischemic myocardium may be possible.The purpose of this study was to observe the changes of regional myocardial perfusion, the epicardial ECG, and the appearance of creatine kinase activity in coronary venous blood in dogs during the 5 hours following occlusion of the left anterior descending coronary artery (LAD). The dose-related effects of nifedipine on these parameters were measured, and the use of this drug to protect the ischemic myocardium is discussed. MethodsTwenty-five mongrel dogs weighing 30-55 kg were anesthetized with intravenous sodium thiopental (Pentothal, 12 mg/kg). Respiration ...

The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion‐induced arrhythmias in anaesthetized rats

“…For example, verapamil does not exhibit a linear log dose-response curve with respect to protection against myocardial enzyme leakage during hypoxia (Nayler et al, 1976) or ischaemia (Yamamoto et al, 1983) nor against the calcium paradox (Hearse et al, 1980). Furthermore, the ability of both prenylamine (Manning et al, 1982) and nifedipine (Selwyn et al, 1979) to reduce the extent of myocardial ischaemic damage is lost at higher concentrations. The reason(s) underlying the loss of this protective action of calcium antagonists at higher concentrations is not known.…”

“…Again, only prenylamine significantly altered heart rate prior to occlusion. It has been suggested by Selwyn et al (1979) that during ischaemia high doses of calcium antagonists may, by virtue of a 'coronary steal' effect, cause a greater inhomogeneity of coronary blood flow between ischaemic and normal regions of the myocardium. If this is the case, it might be anticipated that all calcium antagonists would exhibit the same phenomenon.…”

Nifedipine therapy for patients with threatened and acute myocardial infarction: a randomized, double-blind, placebo-controlled comparison.

“…In addition, calcium blockers may limit the quantity of ischemic myocardium that eventually becomes necrotic whether or not flow is increased via the compromised vessel of supply. This beneficial effect may result from a decrease in oxygen demand through reduction of afterload, 8 an increase in oxygen supply through improved coronary collateral flow,8 9 and/or metabolic benefits in cells exposed to a given ischemic insult. 8 10.…”

The effect of acute regional myocardial ischemia on the angiographic anatomy of coronary arteries.

“…Time-activity graphs were calculated by a Deltron-Nova 1220 digital computer and corrected for the decay of rubidium-81 (half-life 4.56 hours). [8][9][10][11][12] A Wilcoxon test for paired differences was used to test changes in end-diastolic pressure, blood pressure and heart rate. An analysis of variance was used to examine the significance of changes in the regional myocardial activity of krypton-81m.…”