Background Nerve growth factor (NGF) is a neurotrophin that supports the survival and differentiation of sympathetic neurons and its increased expression after myocardial infarct was correlated with cardiac sympathetic hyperinnervation and arrhythmias. of rats (n = 6) with left coronary occlusion Eprosartan for 30 min followed by 120-min reperfusion. The area at risk and infarct to risk ratios were determined from sections stained with 1 % 2 3 5 chloride. Results NGF treatment at doses of 0.015-15 μg/kg with an optimal dose of 0.15 μg/kg given IV before ischemia reduced the infarct size from about 60% at the area of risk to about 25% indicating cardioprotection by about 60%. The infarct-sparing effects of NGF were partially abolished by the inhibition of PI3K and NOS using wortmannin and N(G)-monomethyl-l-arginine respectively. Conclusions We have demonstrated for the first time that NGF attenuates myocardial infarct damage in an in vivo rat model of myocardial regional IRI. This cardioprotective effect is usually proposed to be related to the activities of PI3K and NOS. This suggests that NGF has a potential therapeutic role in the treatment of IRI. Keywords: cardioprotection infarct myocardial ischemia/reperfusion NGF Nerve growth factor (NGF) a member of the neurotrophin family of growth factors plays a crucial function in the nervous system  and is very important in the cross talk between the nervous and cardiovascular systems . Growing evidence has suggested a critical role for NGF during cardiovascular development. NGF is an essential factor in the formation of the heart and a critical regulator of vascular development. Postnatally NGF controls the survival of blood vessel endothelial cells vascular easy muscle cells and heart cardiomyocytes and regulates angiogenesis and vasculogenesis by autocrine and paracrine mechanisms . While many studies have established the role of NGF in cardiac pathophysiology  the hypothesis that NGF plays an important cardioprotective role in myocardial ischemia/reperfusion injury (IRI) has not yet been explored. To determine the effects of NGF on myocardial IRI NGF was administered intravenously (IV) 15 min before ischemia to rats in a series of experiments (n=6 per group) for finding the dose-dependent effect (0.015-15 μg/kg) and for the assessment of the optimal dose. To determine the mechanisms involved the rats were injected with inhibitors of phosphatidylinositol-3 kinase (PI3K) (wortmannin 15 μg/kg) or nitric oxide synthase (NOS) [N(G)-monomethyl-l-arginine (L-NMA) 15 mg/kg] 15 min before the injection of NGF (0.15 μg/kg) – conditions previously reported by us to inhibit these signaling pathways in this rat model [5 6 The principal end point was infarct size expressed either as a Eprosartan percentage of the area at risk (AAR) or the left ventricular area (LVA). The infarct size was 60%±3% of the AAR (Physique 1A) and 30%±2% of the LVA (Physique 1B). A bell-shaped dose-response reduction in infarct size was seen with NGF treatment 0.15 μg/kg Eprosartan being the optimally effective dose. The hearts of treated rats had an infarct size of 24.9%±1.8% of the AAR and 13.8%±1% of the LVA which are approximately 58.5% and 54% reduction in infarct size compared with the control respectively (Determine 1A B). Heart rate and blood pressure were monitored throughout the procedure and there were no significant differences in basal hemodynamic parameters between groups. Mean arterial pressures decreased during ischemia and reperfusion by 35%-45% in all groups ; however there was no significant difference between the groups (Physique 1C D). Physique 1 NGF-induced cardioprotection (A B) and hemodynamic values of mean arterial pressure (C) and heart rate (D) in a rat myocardial ischemia/reperfusion model PI3K is an important mediator of cardioprotection . To determine whether NGF-induced cardioprotection is usually mediated by this pathway we injected IV before IRI wortmannin a PI3K inhibitor alone or in combination DDB2 with NGF. Wortmannin abolished the cardioprotective effect of NGF by 50% but had no effect when given alone. Increased NO produced by activating NOS protects the heart against IRI . To determine whether NGF-induced cardioprotection is usually mediated by this pathway we injected IV before IRI L-NMA a general NOS inhibitor. L-NMA abolished the cardioprotective effect of NGF by 50% but had no effect when given alone. The major finding of this study is that a single treatment with NGF before ischemia significantly reduced the heart Eprosartan infarct size associated with IRI. In addition we.