Hydrogen sulfide (H 2 S) is a novel gaseous signaling molecule that up-regulates antioxidants and antiapoptogens and promotes cellular survival. In the heart, cystathionine gamma-lyase (CSE) is the primary enzyme for endogenous production of H 2 S. We have previously demonstrated that CSE transgenic mice or mice treated with H 2 S are protected against myocardial ischemia/reperfusion (MI/R) injury and heart failure. We hypothesized that CSE knockout mice (KO) would develop increased infarct size following MI/R compared to wild-type (WT) mice. CSE KO mice ( n =12) and WT mice ( n =11) at 12–14 weeks of age were subjected to 45 min of MI and 24 h of R in vivo, at which time the left ventricular (LV) area-at-risk (AAR) and infarct size (INF) were determined with Evan’s blue dye and 2,3,5-triphenyl tetrazolium chloride (TTC) staining ( Fig. 1 ). An additional group of CSE KO mice ( n =12) was subjected to MI/R and received Na 2 S (100 μg/kg) at the time of reperfusion. Western blotting for basal cardiac antioxidant enzyme levels was also performed in separate groups of mice ( n =6 per group). The results show a significant increase in the myocardial INF/AAR of CSE KO mice compared to WT mice (62%±2% vs. 42%±3%, respectively, P <.001). This exacerbation of MI/R injury was attenuated by 50% following Na 2 S therapy at reperfusion (29%±4% INF/AAR, P <.001 vs. CSE KO). However, CSE KO mice failed to demonstrate a significant difference ( P =NS vs. WT) in myocardial tissue levels of thioredoxin (TRX), superoxide dismutase (SOD), heat shock protein 90 (HSP-90) or heme oxygenase-1 (HO-1). This study demonstrates that basal H 2 S production from CSE is critical for protecting the heart during ischemia and reperfusion. Future studies will determine the mechanisms by which CSE KO mice have increased susceptibility to MI/R injury.
