Abstract 947: Hydrogen Sulfide Donor Protects Against Acute Myocardial Ischemia-Reperfusion Injury
Background: Hydrogen sulfide (H2S) has previously been reported to modulate a number of physiological actions including: vasodilation, inhibition of oxidant stress and apoptosis, and reversible inhibition of mitochondrial respiration. We hypothesized that H2S would limit myocardial injury in an in vivo murine model of myocardial ischemia-reperfusion injury (MI-R) and that protection may be mediated via the inhibition of mitochondrial respiration and apoptosis.
Methods: Mice were subjected to 30 min of MI and 24 h of R in vivo. The H2S donor, sodium hydrosulfide hydrate (NaHS), or vehicle was administered i.v. at the time of R. Additionally, cardiac mitochondria were isolated and oxygen consumption was determined. Caspase-3 activity was measured in isolated cardiomyocytes.
Results: Mice receiving NaHS displayed a dose-dependent reduction in infarct size per area-at-risk (INF/AAR). A 100 μg/kg bolus of NaHS maximally reduced INF/AAR by 56%. In correlation, mitochondrial respiration (measured as oxygen consumption) and apoptosis (caspase-3 activity), were also dose-dependently inhibited by NaHS.
Conclusions: This is the first report that hydrogen sulfide protects against MI-R injury in vivo. Our data suggest that H2S protects against MI-R injury possibly by reversibly inhibiting mitochondrial respiration at the time of reperfusion thereby inhibiting mitochondrial oxidant generation and cardiac apoptosis. Furthermore, these data suggest that hydrogen sulfide or its endogenous enzymatic synthesis may be important therapeutic targets in the setting of acute myocardial infarction.