Effect of pretreatment with anipamil on a submaximal calcium paradox in the isolated rat heart.

Successive perfusion of a heart with a Ca(2+)-free and Ca(2+)-containing solution results in irreversible myocardial cell damage: the calcium paradox. Experiments were undertaken to assess whether pretreatment of rats with the new calcium antagonist anipamil (5 mg/kg body weight, twice daily for 5 days) protects the isolated heart against a submaximal calcium paradox. A submaximal calcium paradox was induced by successive perfusion with a Ca(2+)-free solution and a solution containing 0.1 mM Ca2+. Hearts from rats pre-treated with anipamil did not show a negative inotropic effect during control perfusion. During reperfusion in the presence of 0.1 Ca2+, after 10 minutes of Ca(2+)-free perfusion, creatine kinase release in hearts from treated rats was significantly less than in hearts from untreated rats (p less than 0.001). It is suggested that anipamil makes the sarcolemma less sensitive to conformational changes upon Ca2+ repletion.