IMPROVED 4- AND 6-HOUR MYOCARDIAL PRESERVATION BY HYPOXIC PRECONDITIONING

Background A brief hypoxic episode can precondition;myocardium against a subsequent ischemic-reperfusion injury. The present study sought to determine whether intracellular ionic alterations, induced expression of heat-shock proteins (hsps), and/or catalase are involved in the ce llular mechanisms by which hypoxic preconditioning can preserve postis chemic function in a model of prolonged hypothermic storage. Methods a nd Results Two groups of isolated working rat hearts were studied: con trol (CON) and hypoxically preconditioned (HP) hearts. Hearts were arr ested at 4 degrees C with St Thomas' cardioplegic solution and immersi on-stored for either a 4- or 6-hour period. Myocardial function tie, h eart rate, aortic flow, coronary flow, developed pressure, and its fir st derivative dP/dt(max)) was determined at baseline, after preconditi oning, and during reperfusion. At similar time points, myocardial [Na](i), [K+](i), [Mg2+](i), and [Ca2+](i) were measured using an atomic absorption spectrophotometer, and tile induction of hsp 70 and catalas e mRNAs was assayed using Northern blot analysis. After 4 and 6 hours of hypothermic storage, aortic flow, dP/dt(max), and [K+](i) were, inc reased, whereas [Na+](i) and [Ca2+](i) were decreased significantly in the HP group compared with the CON group. Steady state mRNA levels of catalase and hsp 70 were increased from baseline levels only in the H P group, with a peak (2.8- and 2.4-fold versus baseline) after 4 hours of storage. Conclusions Our results indicate that intracellular ionic alterations and upregulation of catalase and hsp 70 gene expression m ay contribute to the mechanisms underlying hypoxic preconditioning, le ading to improved postischemic function during prolonged hypothermic s torage of hearts.