Effect of verapamil on contractile function of the isolated perfused rat heart during postnatal ontogeny

The negative inotropic effect of the calcium antagonist, verapamil, was compared in isolated hearts from 15-, 30-, 45-, 60-, and 90-day-old rats. Electrically paced hearts were perfused in vitro according to Langendorff, either under constant pressure or under constant flow conditions. An intraventricular-pressure curve was measured isovolumetrically and analyzed on-line using a microcomputer. Changes in pressure amplitude and maximum rate of pressure development were evaluated during a stepwise increase of the verapamil concentration in the perfusion solution (10(-9) - 3.3 x 10(-7) mol.l-1). It was found that the sensitivity of cardiac contractile function to verapamil declines gradually in the course of postnatal ontogeny. The higher sensitivity of the developing heart to calcium channel blockade is probably a consequence of a higher functional dependence of the immature myocardium on trans-sarcolemmal calcium influx.