We have previously shown that N-n-butyl haloperidol iodide (F_2) derived from haloperidolreduces ischemia/reperfusion-induced myocardial injury by blocking intracellular Ca~(2+) overload.This studytested the hypothesis that cardio-protection with F2 is associated with an attenuation in the expression ofearly growth response gene 1 (Egr-l).In an in vivo rat model of 60 rain coronary occlusion followed by180 rain of reperfusion,treatment with F_2 significantly reduced myocardial injury evidenced by the reductionin release of plasma creatine kinase,myocardial creatine kinase isoenzyme and lactate dehydrogenase.Incultured neonatal rat cardiomyocytes of hypoxia for 3 h and reoxygenation for 1 h,F2 treatment attenuatednecrotic and apoptotic cell death,as demonstrated by electron microscopy.Concomitant with cardio-protectionby F_2,the increased expression levels of Egr-l mRNA and protein were significantly reduced in myocardialtissue and cultured cardiomyocytes as detected by reverse transcription-polymerase chain reaction,immunohistochemistry and immunocytochemistry.In conclusion,these results suggest that the protectiveeffect of F_2 on ischemia/reperfusion-or hypoxia/reoxygenation-induced myocardial injury might be partlymediated by downregulating Egr-l expression. We have previously demonstrated that Nn-butyl haloperidol iodide (F_2) derived from haloperidolreduces ischemia / reperfusion-induced myocardial injury by blocking intracellular Ca ~ (2+) overload. This studytested the hypothesis that cardio-protection with F2 is associated with an attenuation in the expression of early growth response gene 1 (Egr-1). In an in vivo rat model of 60 min coronary occlusion followed by 180 min of reperfusion, treatment with F_2 significantly reduced myocardial injury evidenced by the reduction in release of plasma creatine kinase, myocardial creatine kinase isoenzyme and lactate dehydrogenase. Cultured neonatal rat cardiomyocytes of hypoxia for 3 h and reoxygenation for 1 h, F2 treatment attenuated necrotic and apoptotic cell death, as demonstrated by electron microscopy. Concomitant with cardio-protection by F_2, the increased expression levels of Egr-1 mRNA and protein were significantly reduced in myocardial tissue and cultured cardiomyocytes as detected by reverse transcri ption-polymerase chain reaction, immunohistochemistry and immunocytochemistry. conclusion. these results suggest that the protective effect of F_2 on ischemia / reperfusion-or hypoxia / reoxygenation-induced myocardial injury might be somewhat reduced by downregulating Egr-1 expression.