Energy metabolism, nitric oxide and superoxide anion production during rabbit heart ex vivo ischemia and reperfusion

ZAOBORNYJ T; BOMBICINO S; IGLESIAS DE; DONATO M; D´ANNUNZIO V; GELPI R,; BOVERIS A; VALDEZ LB

San Francisco, USA.

Congreso; 16th Annual Meeting of the Society for Free Radical Biology and Medicine; 2009

Society for Free Radical Biology and Medicine

Left ventricle mitochondrial function of rabbit hearts exposed to ex vivo ischemia-reperfusion was studied, with special attention to NO and O2·- metabolism. Isolated hearts were perfused according to Langendorff technique. After 15 min of stabilization (0/0), ischemia was induced for 15 min (15/0), followed by 5 or 30 min of reperfusion (15/5 and 15/30). Tissue slice O2 consumption rates were 5% lower after ischemia, and 15 and 40% lower after 5 and 30 min reperfusion. Ischemia and 5 min of reperfusion decreased state 3 and state 4 mitochondrial respiration with malate/glutamate. These effects were not observed with succinate, suggesting that ischemia-reperfusion damages complex I. For complex I activity, a decrease of about 30% was observed for 15/0, and the decline was irreversible with 5 or 30 min of reperfusion. Complex II and IV activities were 15% lower after 15 min of ischemia, but the effect was reversed at 5 and 30 min of reperfusion. O2·- production was enhanced by 100% during ischemia and reperfusion. Mitochondrial NO production was decreased by about 35% in 15/0 and 15/5 hearts. After 30 min of reperfusion mtNOS activity was enhanced, reaching values 24% lower than 0/0 hearts. These results are in accordance with mtNOS functional activity measured through O2 consumption, in the presence of L-arginine or L-NMMA: 58% (0/0), 37% (15/0), 23% (15/5) and 34% (15/30). Endogenous mitochondrial NO and NO-derived species are involved in the bioenergetic regulation observed during ischemia and the impairment of mitochondrial function detected after reperfusion.