Abstract 15326: Transient Extracellular Acidification at the Onset of Reperfusion Decreases Cardiac Injury by Inhibiting Complex I Activity in the Murine Heart
Reversible inhibition of complex I at the onset of reperfusion (REP) decreases cardiac injury in buffer perfused hearts. Complex I activity is decreased when mitochondria are exposed to an acid medium. We propose that transient extracellular acidification during early REP will decrease cardiac injury by inhibiting complex I activity. First, the effect of acidification on respiration was studied using isolated murine cardiac mitochondria. Acidification decreased the rate of oxidative phosphorylation (OXPHOS) with a complex I substrate (glutamate+malate), but not with a complex II substrate (succinate). Thus, acidification selectively blocked respiration through complex I. Next, the role of extracellular acidification in cardiac protection was studied in the intact heart. Langendorff-perfused C57BL/6 mouse hearts underwent 25 min ISC and 60 min REP. In treated hearts, acid buffer (pH 6.6) was perfused for 5 min at the onset of REP followed normal buffer perfusion for 55 min. Acidification improved recovery of LVDP and reduced myocardial infarct size. Next, mitochondria were isolated at 5 min of REP. Acidification treatment markedly improved mitochondrial calcium retention capacity (CRC), indicating a decreased susceptibility to opening of the permeability transition pore. Thus, modulation of mitochondrial complex I activity by acidification decreases cardiac injury by inhibiting permeability transition pore opening during REP.
- © 2011 by American Heart Association, Inc.