INHIBITION OF BICARBONATE TRANSPORT PROTECTS EMBRYONIC HEART AGAINST REOXYGENATION-INDUCED DYSFUNCTION

It has not been well established whether the mechanisms participating in pH regulation in the anoxic-reoxygenated developing myocardium rese mble those operating in the adult. We have specially examined the impo rtance of Na+/K+ exchange (NHE) and HCO3-dependent transports in cardi ac activity after changes in extracellular pH (pH(o)). Spontaneously c ontracting hearts isolated from 4-day-old chick embryos were submitted to single or repeated anoxia (1 min) followed by reoxygenation (10 mi n). The chronotropic, dromotropic and inotropic responses of the heart s were determined in standard HCO3- buffer at pH(o) 7.4 and at pH(o) 6 .5 (hypercapnic acidosis), In distinct experiments, acidotic anoxia pr eceded reoxygenation at pH(o) 7.4. NHE was blocked with amiloride deri vative HMA (1 mu mol/l) and HCO3-dependent transports were inactivated by replacement of HCO3 or blockade with stilbene derivative DIDS (100 mu mol/l). Anoxia caused transient tachycardia, depressed mechanical function and induced contracture, Reoxygenation temporarily provoked c ardiac arrest. atrio-ventricular (AV) block, arrhythmias and depressio n of contractility. Addition of DIDS or substitution of HCO3 at pH(o) 7.4 had the same effects as acidosis per se, i.e. shortened contractil e activity and increased incidence of arrhythmias during anoxia, prolo nged cardioplegia and provoked arrhythmias at reoxygenation. Under ano xia at pH(o) 6.5/reoxygenation at pH(o) 7.4, cardioplegia, AV block an d arrhythmias were all markedly prolonged. Interestingly, in the latte r protocol, DIDS suppressed AV block and arrhythmias during reoxygenat ion, whereas HMA had no effect. Thus, intracellular pH regulation in t he anoxic-reoxygenated embryonic heart appears to depend predominantly on HCO3 availability and transport. Furthermore, pharmacological inhi bition of anion transport can protect against reoxygenation-induced dy sfunction. (C) 1998 Academic Press Limited.