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, California

Congreso; Oxygen Club of California 2010 - World Congress: Oxidants & Antioxidants in Biology; 2010

Oxygen Club of California

We studied left ventricle mitochondrial function of rabbit heart exposed to ex vivo ischemia-reperfusion (Langendorff technique). After 15 min of stabilization, 15 minischemia was induced, followed by 5 or 30 min of reperfusion. Tissue O2 consumption were 20% and 45% lower after 5 and 30 min reperfusion, respectively. Ischemiareperfusion decreased state 3 respiration using malate/glutamate, impairing the RC from 5.4 to 4.7. Hydrogen peroxide production after 30 min of reperfusion was 80% higher than the production detected in control mitochondria. For complex I activity, a decrease of about 20% was observed after 15 min of ischemia, and the decline was maintained with reperfusion. Mitochondrial NO production decreased 35% in 15/0 hearts with a recovery to control values after 30 min reperfusion. This pattern was in agreement with the changes detected in mtNOS functional activity considering malate/glutamate-supported O2 consumption. The mitochondrial level of protein carbonyls (40%), TBARS (50%) and nitrotyrosine (3-fold) were markedly increased after ischemia-reperfusion. This model leads to an acute hypoxia with an early reduction of mitochondrial NO production, releasing cytochrome oxidase inhibition. When heart reoxygenation occurs, mtNOS activity is uptriggered leading to a NO burst, increasing mitochondrial O2 and ONOO- production. During reperfusion mitochondria develop a condition named “complex I syndrome” in which enzymatic complex I inactivation is associated with protein nitration and oxidative damage to proteins and phospholipids.