BENEFICIAL-EFFECTS OF MYOCYTE PRECONDITIONING ON CONTRACTILE PROCESSES AFTER CARDIOPLEGIC ARREST

Background. Myocardial preconditioning, which can be achieved through short intervals of ischemia or hypoxia followed by reperfusion, protec ts the myocardium with subsequent prolonged periods of ischemia. Accor dingly, the present study tested the hypothesis that hypoxic precondit ioning before cardioplegic arrest would have direct and beneficial eff ects on myocyte contractile processes with reperfusion. Methods. Left ventricular porcine myocytes (n = 335) were randomly assigned to one o f three treatments: normothermia, maintained in cell media (37 degrees C, 2 hours); cardioplegia, hyperkalemic arrest (24 mEq K+, 4 degrees C, 2 hours) followed by normothermic reperfusion; preconditioning hypo xia (20 minutes) and reperfusion (20 minutes), and then followed by ca rdioplegic arrest and rewarming. Myocyte velocity of shortening was me asured using computer-assisted videomicroscopy at baseline and with be ta-adrenergic receptor stimulation with isoproterenol (25 nmol/L). Res ults. In the cardioplegia group, myocyte function was reduced at basel ine (22 +/- 1 versus 57 +/- 2 mu m/s) and with beta-adrenergic recepto r stimulation (81 +/- 5 versus 156 +/- 7 mu m/s) compared to normother mic controls (p < 0.05). Preconditioning improved myocyte function at baseline (38 +/- 2 mu m/s) and with beta-adrenergic receptor stimulati on (130 +/- 6 mu m/s) compared to the cardioplegic alone group (p < 0. 05). Conclusions. The important findings from this study are twofold. First, preconditioning can be induced directly at the level of the myo cyte, independent of nonmyocyte populations and extracellular influenc es. Second, myocyte preconditioning provides protective effects on myo cyte function and beta-adrenergic responsiveness after cardioplegic ar rest and rewarming. These findings suggest that preconditioning may pr ovide a novel approach in protecting myocyte contractile processes dur ing cardioplegic arrest.