COMPLEX I SYNDROME IN MYOCARDIAL STUNNING AND THE EFFECT OF ADENOSINE

VALDEZ LB; ZAOBORNYJ T; BOMBICINO SS; IGLESIAS DE; BOVERIS A; DONATO M; D'ANNUNZIO V; BUCHHOLZ B; GELPI R

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Año: 2011 vol. 51 p. 1203 - 1212

0891-5849

Isolated rabbit hearts were exposed to ischemia (I; 15 min) and reperfusion (R; 5?30 min) in a model of stunned myocardium. I/R decreased left-ventricle O2 consumption (46%) and malate?glutamate-supported mitochondrial state 3 respiration (32%). Activity of complex I was 28% lower after I/R. The pattern observed for the decline in complex I activity was also observed for the reduction in mitochondrial nitric oxide synthase (mtNOS) biochemical (28%) and functional (50%) activities, in accordance with the reported physical and functional interactions between complex I and mtNOS. Malate?glutamate-supported state 4 H2O2 production was increased by 78% after I/R. Rabbit heart Mn-SOD concentration in the mitochondrial matrix (7.4±0.7 μM) was not modified by I/R. Mitochondrial phospholipid oxidation products were increased by 42%, whereas protein oxidation was only slightly increased. I/R produced a marked (70%) enhancement in tyrosine nitration of the mitochondrial proteins. Adenosine attenuated postischemic ventricular dysfunction and protected the heart from the declines in O2 consumption and in complex I and mtNOS activities and from the enhancement of mitochondrial phospholipid oxidation. Rabbit myocardial stunning is associated with a condition of dysfunctional mitochondria named ?complex I syndrome.? The beneficial effect of adenosine could be attributed to a better regulation of intracellular cardiomyocyte Ca2+ concentration.