GLIBENCLAMIDE DOES NOT ABOLISH THE PROTECTIVE EFFECT OF PRECONDITIONING ON STUNNING IN THE ISOLATED PERFUSED RAT-HEART

Objective: The aim was to determine if the beneficial effects of preco nditioning would be affected by inhibiting ATP sensitive potassium (K( ATP)) channels in the isolated, perfused rat heart. Methods: The effec ts of inhibiting K(ATP) channels with glibenclamide (10 muM) were eval uated on ionic alterations and recovery of function after 30 min ischa emia in non-preconditioned hearts and in hearts that had been precondi tioned with four intermittent periods of 5 min ischaemia each separate d by 5 min of reflow. [Ca2+]i, pH(i), and high energy phosphate levels were measured using F-19 and P-31 nuclear magnetic resonance during t he preconditioning periods of ischaemia, during 30 min of ischaemia, a nd during reflow, in the presence and absence of 10 muM glibenclamide. Results: High energy phosphate contents were decreased during the pre conditioning period to a greater extent in glibenclamide treated heart s and the onset of contracture was hastened during the subsequent 30 m in period of sustained ischaemia. However, glibenclamide (10 muM) did not abolish the protective effects of preconditioning on ion accumulat ion during ischaemia or on postischaemic recovery of contractile funct ion. Recovery of left ventricular developed pressure (as % of initial value) following 30 min of ischaemia was 74(SEM 5)% in the preconditio ned hearts without drug and 62(4)% in the preconditioned hearts with g libenclamide, while recovery was 25(5)% in the non-preconditioned hear ts without drug and 19(2)% in the non-preconditioned hearts with drug. The alterations in [Ca2+]i and pH(i) during ischaemia were similar in the glibenclamide treated and untreated preconditioned hearts and in both cases were less marked than in the non-preconditioned untreated h earts. Conclusions: Thus, although inhibition of K(ATP) channels accel erates high energy phosphate depletion during the preconditioning peri od, this does not result in accentuation of the ionic derangements dur ing a subsequent sustained period of ischaemia and does not abolish th e protective effect of preconditioning on stunning in the isolated rat heart.