EFFECTS OF PRECONDITIONING ON REPERFUSION ARRHYTHMIAS, MYOCARDIAL FUNCTIONS, FORMATION OF FREE-RADICALS, AND ION SHIFTS IN ISOLATED ISCHEMIC REPERFUSED RAT HEARTS/

The effects of preconditioning on development of reperfusion-induced v entricular fibrillation (VF), ventricular tachycardia (VT), free radic al 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; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subj ected to one cycle of preconditioning, consisting of 5-min global isch emia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of p reconditioning (5-min ischemia plus 10-min reperfusion) followed by 30 -min ischemia plus 30-min reperfusion. The incidences of VF and VT wer e 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 formatio n, as an indirect marker of free radicals, was observed after 30-min i schemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the n onpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreco nditioned 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 wh en 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 fourfold accumulation of myocardial Na and Ca, respectively, and a decrease of similar to 50% in both K an d Mg. Four cycles of preconditioning significantly protected hearts ag ainst ischemia, reperfusion-induced myocardial Na and Ca accumulation, and K and Mg loss. Our results show that preconditioning can modify t he ischemia/reperfusion-induced deleterious ion shifts and free radica l formation and consequently protect the heart against life-threatenin g arrhythmias.