Calcium antagonists may protect against postischemic
reperfusion injury of the heart, but neither the time and mode of action leading to cardioprotection is resolved, nor is the generality of this effect proven. Accordingly, the functional and metabolic influence of four different Ca2+-antagonists (
diltiazem, 3x10(-8)
M; nifedipine, 3x10(-9) M;
amlodipine, 3x 10(-9) M;
barnidipine, 3x10(-11) M) was examined in preparations of guinea pig hearts (n=7/group) performing pressure-volume work after being subjected to low-flow
ischemia (30 min) and reperfusion (35 min). The drugs were applied throughout the study at concentrations without negative inotropic or chronotropic effect, as would be mandatory for any therapeutic application, and without overt coronary dilatation. All
calcium antagonists improved postischemic recovery of external heart work: from 42% in controls (post- vs. preischemic value) to 59% for
diltiazem, 61% for
nifedipine, 65% for
amlodipine, and 73% for
barnidipine (all P<0.05). Efficiency of myocardial performance (work in relation to oxygen consumption) was low in postischemic controls (8% of total energy equivalents), but significantly improved in treated hearts, especially by
barnidipine (15% efficiency). Release of
lactate dehydrogenase in the first 5 min of reperfusion, a sign of cell damage, increased from basal (65 mU/min) to 208 mU/min in controls. This increase was fully suppressed by all drugs tested. Myocardial release of
lactate and of
purine catabolites of
adenine nucleotides (markers of anaerobic metabolism) was markedly reduced by Ca2+-antagonists. Interestingly, these metabolic effects were evident not only in the reperfusion phase, but already in the period of low-flow
ischemia. Oxidative consumption of
pyruvate was enhanced, whereas coronary flow and heart rate showed no postischemic effect of treatment. These findings on isolated guinea pig hearts suggest that Ca2+-antagonists generally improve postischemic pump function and aerobic metabolism without any requirements for negative inotropic action or coronary dilatation. The protective effects seemed to rely on an attenuation of both ischemic stress and
reperfusion damage. This could implicate a benefit from prophylactic use of Ca2+-antagonists in patients at risk for
myocardial ischemia.