Comparative effects of calcium channel blocking agents and varying extracellular calcium concentration on hypoxia/reoxygenation and ischemia/reperfusion-induced cardiac injury.

OUr study was designed to evaluate and compare the effects of three structurally different calcium channel blocking drugs, verapamil (10 and 100 ng/ml), diltiazem (1 and 10 micrograms/ml) and nifedipine (10 and 100 ng/ml), and altering calcium concentration on two models of heart damage, hypoxia/reoxygenation and ischemia/reperfusion (60 min/15 min) of isolated rat hearts. The increase in creatine phosphokinase release by hypoxia and reoxygenation was significantly decreased by treatment with all three drugs. Reoxygenation-induced enzyme efflux was enhanced by a 3-fold elevation in external CaCl2 and depressed by a two-thirds calcium reduction. In contrast, elevation of calcium concentration had no significant effect on postischemia reperfusion-induced creatine phosphokinase efflux whereas "low calcium" decreased release during reperfusion. Two drugs which effectively reduced reperfusion- (nifedipine) or reoxygenation- (diltiazem) induced enzyme release as well as reducing calcium concentration were evaluated to determine during which phase of perfusion these treatments exerted their beneficial effect. The reduction of creatine phosphokinase release during reoxygenation by diltiazem was dependent on the drug's presence during the hypoxia phase of perfusion whereas low calcium (either reoxygenation or reperfusion) or nifedipine treatment (reperfusion) was protective irrespective of whether the treatment was present during hypoxia/ischemia or reoxygenation/reperfusion. The reduction in enzyme release was associated with an enhanced mechanical recovery and a reduction in arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)