Objective By using cardiac ischemia reperfusion model, the muscarinic receptor path way of cardiac signal conduction in both young and aged myocardium was studied. The aim was to study the pathogenesis of ischemia reperfusion injury in aged myocardium. Methods 20 dogs (15～20 kg) were randomly divided into two groups: group A (young, 3～4 years old, n=10), group B (old, 7～8 years old, n=10). All dogs underwent 60 minutes of global ischemia and 30 minutes of reperfusion under cardiopulmonary bypass (CPB). A tunnel was inserted through the left ventricular apex, to measure the LVEDP、+dp/dt、-dp/dt and ECG. . Myocardial specimens were collected at the beginning of reperfusion, 30 min after reperfusion and 60 min after reperfusion. Myocardium was prepared or studied of density of muscarinic receptor, G protein level, cGMP, guanylate cyclase activity, value of NO, protein level of eNOS, mRNA level of iNOS and eNOS. Results (1) Group B had higher LVEDP but lower +dp/dt max and -dp/dt max than group A in each stage. After CPB, the LVEDP showed no difference between pre and post surgery in two groups, while +dp/dt max and -dp/dt max were decreased in both groups, more significantly in group B. (2) At 30 min and 60 min after reperfusion, the density of M receptor was significantly increased in group B than that in group A. (3) There was no significant difference in Gs pre and post surgery in group A. Compared with group B, the level of Gi decreased significantly after the reperfusion in group A. There were decreasing in Gs and Gi after reperfusion in group B, more greater in the former. The ratio of Gi/Gs in group B was much higher than that in group A. (4) Compared with group A, the mRNA level of eNOS and protein level of eNOS decreased more significantly in group B during each stage of reperfusion. After ischemia reperfusion, the mRNA level of iNOS, NO, cGMP and guanylate cyclase activity were obviously increased in group B than that in group A.Conclusion (1) After the cardiac surgery in elder model, the M receptor path way increased significantly, which is negatively correlated with cardiac function, hence promote the ischemia reperfusion injury in elder myocardium. (2) In the ischemia reperfusion injury in elder myocardium, higher vagotonic does more harm to the old myocardium through NO and NO cGMP pathway.