Preconditioning with Bay 60–2770, An Activator of Soluble Guanylate Cyclase, Attenuates Myocardial Infarction in eNOS Knockout Mice

Our previous studies showed that soluble Guanylate Cyclase (sGC) activation protects against postischemic intestinal injury when used as a preconditioning stimulus in wild type, heme‐oxygenase‐1 KO and eNOS KO (eNOS −/− )mice. The aim of this study was to determine whether a similar protective effect of sGC activation by Bay60–2770 (Bay 60) would occur in postischemic cardiac injury. Infarct size (% LV), assessed by 2,3,5‐triphenyltetrazolium chloride (TTC) staining, was significantly increased in eNOS −/− mice after 30 min left anterior descending coronary artery (LAD) ischemia and 24 hr reperfusion as compared with eNOS −/− sham mice (p < 0.001). Bay 60 treatment (300ug/kg, ip bolus, 24hr prior to LAD ischemia) significantly attenuated I/R‐induced increase in infarct size (p < 0.05) in eNOS −/− mice. Serum Troponin‐I (cTnI), a marker of myocardial injury, after 30 min LAD ischemia and at 4 hr reperfusion, was markedly elevated in eNOS −/− mice, compared with eNOS −/− sham mice (p < 0.01). Preconditioning with Bay 60 24hr prior to cardiac I/R did not prevent the increase in cTnI levels. These findings indicate that Bay 60 preconditioning 24hr prior to cardiac I/R limits the size of the evolving infarct area at 24 hr of perfusion independently of eNOS and factors leading to early release of cTnI. Supported by a grant from the NIH (AA‐014945). BAY 60–2770 was a gift from Bayer Schering Pharma AG.