The hallmarks of alcoholic cardiomyopathy include compromised cardiac morphology and myocardial contractility. This is coincided with our observations of reduced myocardial contraction and enlarged Isorhychophylline cardiomyocyte area in ethanol-challenged murine hearts. Furthermore, data from our present study revealed overt mitochondrial damage and apoptosis following ethanol challenge, which may contribute to the ethanol-elicited myocardial histological and functional alterations. More strikingly, our study provided evidence for the first time that cardiac mitochondrial damage and apoptosis following ethanol exposure may be exacerbated by overexpression of ADH, which produces much more local acetaldehyde in the hearts consistent with the previous findings. These observations are in favor of the notion that facilitated ethanol metabolism via ADH enzyme exacerbates ethanol-induced myocardial dysfunction, histological alteration and apoptosis possibly related to mitochondrial damage. Data from our present study revealed that ADH accentuated ethanol-induced cardiomyocyte hypertrophy with little change in gross weight of the heart or expression of the hypertrophic marker ANP. These seemingly conflicting data may be a concerted result from hypertrophy and apoptosis in murine cardiomyocytes. An earlier study using the same ADH transgenic mice noted overt cardiac hypertrophy and upregulated expression of the hypertrophic markers a-skeletal actin and atrial natriuretic factor in ADH but not FVB mice after 10 weeks of alcohol feeding. To this end, it is not surprising for the lack of change in ANP in response to acute ethanol challenge in our experimental settings. The enlarged cardiomyocyte size may be a result of certain hemodynamic changes following acute ethanol challenge or binge drinking although further study is Sibiricose-A6 warranted. Acetaldehyde is known to trigger both oxidative stress and apoptosis via activation of stress signaling such as c-Jun phosphorylation. This is supported by our experimental findings of elevated O2N2 production and TUNEL-positive apoptotic cells in ADH murine hearts following ethanol challenge.