Thioredoxin-1 ameloriates post-ischemic ventricular and mithochondrial dysfunction (myocardial stunning) in isolated mice hearts

D'ANNUNZIO V; PEREZ V; VALDEZ LB; ZAOBORNYJ T; BOVERIS A; GELPI RJ

Buenos Aires

Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine. South American Group (VIII SFRBM-SAG); 2013

Although thioredoxin-1 protects the heart from ischemia/reperfusion (I/R) injury reducing infarct size, no studies assessing the role of this enzyme on stunned myocardium were performed. The aim was to evaluate the effect of myocardial stunning on ventricular and mitochondrial function using wild type mice (wt), transgenic mice overexpressing cardiac thioredoxin-1 (Trx-1) and transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1. Langendorff-perfused hearts were subjected to I/R (15 min/30 min). After 30 min of reperfusion, Trx-1 improved left ventricular developed pressure compared to wt and DN (60±7% vs. 29±6% and 31±8%). Trx-1 showed an improvement in isovolumic relaxation during reperfusion (wt: 60±12%, DN:64±14% vs. Trx-1:17±5%). Trx-1also improved myocardial stiffness but interestingly DN aggravated this variable increase compared with wt and Trx-1 (Trx-1: 117±23% vs. wt:27±9% and DN:22±3%). State 3 mitochondrial O2 consumption was impaired by 10% after I/R in wt and by 24% in DN. However, Trx-1 state 3 respiration was unaffected by I/R. These changes were accompanied by 13% (wt) and 37% (DN) decreases in respiratory control. ADP/O values were 24% (wt) and 37% (DN) lower than wt before I/R. Interestingly after I/R Trx-1 showed unchanged ADP/O values. The results suggest that Trx-1 is involved in a protective pathway that ameliorates the effects of myocardial stunning, probably by improving mitochondrial function.