EFFECTS OF VERAPAMIL AND RYANODINE ON ACTIVITY OF THE EMBRYONIC CHICKHEART DURING ANOXIA AND REOXYGENATION

Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment an d sarcoplasmic reticulum (SR) are involved to the same extent in the d ysfunction of the anoxic-reoxygenated immature heart has not been inve stigated. Spontaneously contracting hearts isolated from 4-day-old chi ck embryos were submitted to repeated anoxia (1 min) followed by reoxy genation (5 min). Heart rate, atrioventricular propagation velocity, v entricular shortening, velocities of contraction and relaxation, and i ncidence of arrhythmias were studied, recorded continuously. Addition of verapamil (10 nM), which blocks selectively sarcolemmal L-type Ca2 channels, was expected to protect against excessive entry of extracel lular Ca2+, whereas addition of ryanodine (10 nM), which opens the SR Ca2+ release channel, was expected to increase cytosolic Ca2+ concentr ation. Verapamil (a) had no dromotropic effect by contrast to adult he art, (b) attenuated ventricular contracture induced by repeated anoxia , (c) shortened cardioplegia induced by reoxygenation, and (d) had rem arkable antiarrhythmic properties during reoxygenation specially. On t he other hand, ryanodine potentiated markedly arrhythmias both during anoxia and at reoxygenation. Thus despite its immaturity, the SR seems to be functional early in the developing chick heart and involved in the reversible dysfunction induced by anoxia-reoxygenation. Moreover, Ca2+ entry through L-type channels appears to worsen arrhythmias espec ially during reoxygenation. These findings show that the Ca2+-handling systems involved in irregular activity in immature heart, such as the embryonic chick heart, may differ from those in the adult.