Effects of Preconditioning on Reperfusion Arrhythmias, Myocardial Functions, Formation of Free Radicals, and Ion Shifts in Isolated Ischemic/Reperfused Rat Hearts

Abstract

Summary: The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; grou II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 ± 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 ± 0.1 to 0.35 ± 0.02 and 0.26 ± 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid. In nonpreconditioned ischemic hearts, 30-min ischemia followed by 30-min reperfusion resulted in three and four-fold accumulation of myocardial Na and Ca, respectively, and a decrease of ∽50% in both K and Mg. Four cycles of preconditioning significantly protected hearts against ischemia, reperfusion-induced myocardial Na and Ca accumulation, and K and Mg loss. Our results show that preconditioning can modify the ischemia/reperfusion-induced deleterious ion shifts and free radical formation and consequently protect the heart against life-threatening arrhythmias.