Myocardial protection during ventricular fibrillation by reduction of proton-driven sarcolemmal sodium influx.

Although the inhibition of proton-driven sarcolemmal sodium influx ameliorates ischemic injury in the quiescent myocardium, the effects when ventricular fibrillation is present are largely unknown. We used an isolated rat heart model to investigate whether inhibition of the sodium-hydrogen exchanger isoform-1 (with the benzoylguanidine derivatives HOE-694 and cariporide) with or without concomitant inhibition of the sodium-bicarbonate co-transporter (with perfusate buffered with N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid [HEPES]) during ischemia and ventricular fibrillation could ameliorate functional myocardial abnormalities presumed to limit cardiac resuscitability. Ischemic contracture, which typically develops during ventricular fibrillation, was ameliorated by HOE-694 when either a bicarbonate-buffered (20 +/- 7 mm Hg vs 15 +/- 5 mm Hg, P <.05) or a HEPES-buffered (14 +/- 5 mm Hg vs 10 +/- 3 mm Hg, P <.04) perfusate was used. Maximal amelioration occurred when cariporide and HEPES-buffered perfusate were used simultaneously (25 +/- 14 mm Hg vs 11 +/- 3 mm Hg, P <.01), and this was accompanied by lesser leftward shifts of the end-diastolic pressure-volume curves after defibrillation. Intramyocardial sodium increases of 76% during ischemia and ventricular fibrillation (P <.05) were ameliorated by the sodium-influx-limiting interventions. Thus interventions limiting sarcolemmal sodium influx during ischemia and ventricular fibrillation may facilitate successful resuscitation from ventricular fibrillation.