Complex I syndrome in rabbit heart submitted to ischemia-reperfusion: effect of adenosine

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

Puert Madryn

Congreso; XLVI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology – SAIB; 2010

SAIB

Isolated and perfused rabbit hearts were exposed to 15 min ischemia and 5 or 30 min reperfusion. Ischemia-reperfusion (I/R) decreased left ventricle O2 consumption (46%) and malate-glutamate supported state 3 respiration (32%) with no changes in state 4 respiration. Mitochondrial complex I activity, but not complexes II and IV, was 28% lower after I/R. Mitochondrial NO production decreased 28%, with a diminished mtNOS functional activity using malate-glutamate as substrate, without modifications in mtNOS expression. State 4 H2O2 production with malate-glutamate was increased by 77% from controls after 30 min of reperfusion. Mitochondrial phospholipid oxidation products (TBARS) were increased (42%), whereas protein oxidation was slightly increased. In addition, there was a 50% increase in tyrosine nitration of the mitochondrial proteins. I/R in the isolated rabbit heart leads to a condition of dysfunctional mitochondria, named “complex I syndrome”, with decreased O2 uptake and complex I activity and increased H2O2 production, oxidation products content and protein nitration. Supplementation with adenosine in the Krebs-Henseleit perfusion solution attenuated post-ischemic ventricular dysfunction and protected the tissue from the mitochondrial alterations observed, this could be attributed to preservation of ATP levels associated to a regulation of the cardiomyocytes Ca2+ concentration.