Acute
ethanol exposure depresses ventricular contractility and contributes to
alcoholic cardiomyopathy in both men and women chronically consuming
ethanol. However, a gender-related difference in the severity of
myopathy exists with female being more sensitive to
ethanol-induced tissue damage.
Acetaldehyde (ACA), the major oxidized product of
ethanol, has been implicated to play a role in the pathogenesis and gender-related difference of
alcoholic cardiomyopathy, possibly due to its direct cardiac effect and interaction with
estrogen. This study was designed to compare the effects of cardiac overexpression of
alcohol dehydrogenase (ADH), which converts
ethanol into ACA, on the cardiac contractile response to
ethanol in ventricular myocytes isolated from age-matched adult male and female transgenic (ADH) and wild-type (FVB) mice. Mechanical properties were measured with an IonOptix SoftEdge system. ACA production was assessed by gas chromatography. The ADH myocytes from both genders exhibited similar mechanical properties but a higher efficacy to produce ACA compared to FVB myocytes. Exposure to
ethanol (80-640 mg/dl) for 60 min elicited concentration-dependent decrease of cell shortening in both FVB and ADH groups. The
ethanol-induced depression on cell shortening was significantly augmented in female but not male ADH group. ADH transgene did not exacerbate the
ethanol-induced inhibition of maximal velocity of shortening/relengthening in either gender. In addition, neither
ethanol nor ADH transgene affect the duration of shortening and relengthening in male or female mice. These data suggest that females may be more sensitive to ACA-induced cardiac contractile depression than male, which may attribute to the gender-related difference of
alcoholic cardiomyopathy.