To assess whether the prophylactic administration of
anipamil, a new
calcium antagonist, protects the heart against the effects of
ischemia and reperfusion, rats were injected intraperitoneally twice daily for 5 days with 5 mg/kg
body weight of this
drug. The heart was then isolated and perfused by the Langendorff technique.
Phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor myocardial energy metabolism and intracellular pH during control perfusion and 30 min of total
ischemia (37 degrees C), followed by 30 min of reperfusion. Pretreatment with
anipamil altered neither left ventricular developed pressure under normoxic conditions nor the rate and extent of depletion of
adenosine triphosphate (
ATP) and
creatine phosphate during
ischemia. Intracellular acidification, however, was attenuated. On reperfusion, hearts from
anipamil-pretreated animals recovered significantly better than untreated hearts with respect to replenishment of
ATP and
creatine phosphate stores, restitution of low levels of intracellular
inorganic phosphate and recovery of left ventricular function and coronary flow. Intracellular pH recovered rapidly to preischemic levels, whereas in untreated hearts a complex intracellular
inorganic phosphate peak indicated the existence of areas of different pH within the myocardium. It is concluded that
anipamil pretreatment protects the heart against some of the deleterious effects of
ischemia and reperfusion. Because this protection occurred in the absence of a negative inotropic effect during normoxia, it cannot be attributed to an energy-sparing effect during
ischemia. Therefore, alternative mechanisms of action are to be considered.