Complex I syndrome in isolated rabbit heart subjected to ischemia-reperfusion

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

Santa Bárbara

Congreso; Annual Meeting of Oxygen Club of California. 2010 World Congress: Oxidants & Antioxidants in Biology; 2010

Oxygen Club of California

The effects of ischemia-reperfusion on left ventricle mitochondrial function were studied in isolated rabbit heart using the Langendorff technique with 15 min of stabilization, 15 min of ischemia and 5 and 30 min of reperfusion. Tissue O2 consumption, mitochondrial state 3 respiration with malate-glutamate, and complex I activity were similarly decreased, by 20-25% and 40-45%, after 5 and 30 min reperfusion, respectively. Hydrogen peroxide production after 30 min of reperfusion was 80% higher than the H2O2 production in control mitochondria. Mitochondrial NO production decreased 35% in ischemic hearts with a recovery to control values during reperfusion. The pattern of mtNOS biochemical activity was in agreement with the changes in mtNOS functional activity in malate/glutamate-supported O2 consumption. The mitochondrial level of protein carbonyls (40%), TBARS (50%) and nitrotyrosine (3-fold) were markedly increased after the process of ischemia-reperfusion. This experimental model shows an early reduction of mitochondrial NO production during acute hypoxia, which may release NO-mediated cytochrome oxidase inhibition. In reoxygenation, mtNOS activity is up-triggered, increasing mitochondrial NO, O2- and ONOO- productions. During reperfusion, mitochondria develop to a condition named “complex I syndrome” in which enzymatic complex I inactivation is associated with protein nitration and oxidative damage to proteins and phospholipids.