Interaction of halothane and verapamil in isolated papillary muscle

The combined depressant effects of verapamil and halothane on myocardial contractility were studied using isolated papillary muscle from the rabbit. Verapamil alone (0.5 microM) significantly decreased peak developed tension (PDT) by 15 +/- 2%, time to peak tension (TPT) by 10 +/- 1%, and maximum rate of increase of tension (+dT/dt) by 5 +/- 1%, but not maximum rate of decrease of tension (-dT/dt). Halothane alone (0.8%) significantly decreased PDT by 56 +/- 2%, TPT by 11 +/- 2%, +dT/dt by 53 +/- 2%, and -dT/dt by 56 +/- 2%. During the exposure period, the combination of verapamil and halothane together produced a simple additive effect (no significant interaction effect by two-way analysis of variance), with PDT decreased by 68 +/- 2%, TPT by 20 +/- 3%, +dT/dt by 62 +/- 2%, and -dT/dt by 65 +/- 2%. The reversibility of halothane-induced depression was also studied. Peak developed tension showed complete reversibility 30 min after discontinuing halothane. In the presence of verapamil, however, the reversibility of halothane-induced depression was not complete, and significant residual depression of PDT (19 +/- 3%) was observed. We conclude that the acute depressant effect of verapamil plus halothane in isolated papillary muscle is additive, but reversibility of halothane-induced depression may be impaired or prolonged in the presence of verapamil.