Background/Aim: Re-perfusion strategies are the current standard therapy for acute myocardial infarction, despite the spectrum of re-perfusion-associated pathologies that may contribute to irreversible myocardial injury. The aim of present study is to clarify the alterations in intrinsic cardiac functions in response to cardiac ischemic arrest followed by re-perfusion in isolated hearts perfused with nitric oxide (NO) donor, L-arginine, or NO inhibitor, Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), to shed light on the possible role of NO in re-perfusion process. Methods: Cardiac activities of hearts isolated from Adult albino rats of both sexes were studied on Langendorff preparation under basal conditions and during 30 min re-perfusion following 30 min of total global ischemia. Rats were randomly allocated into three groups; control and L-arginine or L-NAME infused heart groups. Both L-arginine and L-NAME were infused over 20 min during the baseline activity before induction of total global ischemia. Thereafter, cardiac tissue levels of malondialdhyde, catalase and nitrite were assessed. Results: Compared to the control, both L arginine and L-NAME infused hearts showed increased basal chronotropy and myocardial flow rate. Significantly depressed basal inotropic state was only observed in L-arginine group. The three studied groups demonstrated significant deterioration in the inotropic activity and compromised myocardial flow rate during the whole period of reperfusion. L-arginine infused hearts demonstrated depressed inotropy and chronotropy, weak systolic and diastolic functions with compromised myocardial flow at early 5 min of reperfusion, yet with significantly higher myocardial flow rate % recovery by the end of reperfusion (82.7% ±3.01 vs. 56.4% ±2.32 in control and 62.6% ±2.17 in L-NAME). The chronotropic activity was maintained in both the control and L-NAME infused hearts. Cardiac tissue NO showed the highest level in L-arginine group and the lowest level in L-NAME one. Both catalase and MDA were insignificantly changed among the three studied groups. Conclusion: Reducing NO availability by L-NAME revealed mild impact on the ischemia re-perfusion induced contractile dysfunction. Excess NO worsens cardiac performance at early re-perfusion. However, it may have potentially protective effect by acquiring higher the myocardial flow rate during the reperfusion. Keywords: Cardiac arrest, ischemia/re-perfusion, L-arginine, L-NAME, nitric oxide.