Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia–reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (–20%) and rate pressure product (–15%) in SIRT3−/− mice. Mitochondrial state 3 respiration (–15%), ATP synthesis (–39%), and ATP/O ratios (–29%) were decreased in hearts of SIRT3−/− mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3−/− 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3−/− 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3−/− mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3−/− mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.
