Beneficial effects of myocyte preconditioning on contractile processes after cardioplegic arrest

Myocardial precondition, which can be achieved through short intervals of ischemia or hypoxia followed by reperfusion, protects the myocardium with subsequent prolonged periods of ischemia. Accordingly, the present study tested the hypothesis that hypoxic preconditioning before cardioplegic arrest would have direct and beneficial effects on myocyte contractile processes with reperfusion.

Left ventricular porcine myocytes (n = 335) were randomly assigned to one of 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, hypoxia (20 minutes) and reperfusion (20 minutes), and then followed by cardioplegic arrest and rewarming. Myocyte velocity of shortening was measured using computer-assisted videomicroscopy at baseline and with beta-adrenergic receptor stimulation with isoproterenol (25 nmol/L).

In the cardioplegia group, myocyte function was reduced at baseline (22 +/- 1 versus 57 +/- 2 microns/s) and with beta-adrenergic receptor stimulation (81 +/- 5 versus 156 +/- 7 microns/s) compared to normothermic controls (p < 0.05). Preconditioning improved myocyte function at baseline (38 +/- 2 microns/s) and with beta-adrenergic receptor stimulation (130 +/- 6 microns/s) compared to the cardioplegic alone group (p < 0.05).

The important findings from this study are twofold. First, preconditioning can be induced directly at the level of the myocyte, independent of nonmyocyte populations and extracellular influences. Second, myocyte preconditioning provides protective effects on myocyte function and beta-adrenergic responsiveness after cardioplegic arrest and rewarming. These findings suggest that preconditioning may provide a novel approach in protecting myocyte contractile processes during cardioplegic arrest.