Nerve growth factor reduces myocardial ischemia/reperfusion injury in rat hearts

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. However, it is unclear whether NGF protects the heart during infarct. In this study, we sought to address this issue in rat heart exposed to ischemia/reperfusion injury (IRI). Methods: NGF was administered intravenously (IV), 15 min before ischemia, at different concentrations in the absence or presence of inhibitors of phosphatidylinositol- 3 kinase (PI₃K) or nitric oxide synthase (NOS) in different groups of rats (n = 6) with left coronary occlusion 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-triphenylterazolium 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 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.