ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of exogenous carbon monoxide (CO) in protection of rat hearts from ischemia/reperfusion injury and its underlying mechanisms.</p><p><b>METHODS</b>Cardiac contractility, lactate dehydrogenase(LDH), creatine kinase(CK) and infarct area were analyzed by the Langendorff isolated rat hearts. All isolated hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion.</p><p><b>RESULTS</b>Perfusion with 25 micromol/L of CORM-2 (an exogenous CO releaser) during the first 10 min of reperfusion prevented the increase in LVEDP and decrease in LVDP, +dp/dt(max) in isolated ischemia/reperfusion hearts. CORM-2(25 micromol/L) had no effect on the changes of coronary flow, but it really inhibited the release of LDH and CK, and also reduced the infarct size. Perfusion with 10 micromol/L of CORM-2 decreased the LDH, CK and infarct size, but it did not improve the contractility of ischemia/reperfusion hearts. However, perfusion with 100 micromol/L of CORM-2 exacerbated the injury induced by ischemia/reperfusion. Pretreatment of a NOS inhibitor L-NAME and a HO-1 inhibitor ZnPP partly abolished the protection effect of CORM-2(25 micromol/L) on LVEDP, and L-NAME and a GC inhibitor methylene blue could also cancel the enhance of LVDP and +dp/dt(max) incuced by CORM-2. All of the inhibitor (methylene blue, L-NAME, a mitoK(ATP )channel blocker 5-HD and ZnPP) could partly enlarge infarct area compared with CORM-2 treatment.</p><p><b>CONCLUSIONS</b>Exogenous CO could protect heart from ischemia/reperfusion injury. The cardiac protection of CO might be through NOS-cGMP and HO-1 pathway, and the activation of mitoK(ATP)channel might be also involved in.</p>