CHRONIC ALCOHOL-INDUCED CHANGES IN CARDIAC CONTRACTILITY ARE NOT DUE TO CHANGES IN THE CYTOSOLIC CA2+ TRANSIENT

Long-standing heavy alcohol consumption acts as a chronic stress on th e heart. It is thought that alcohol-induced changes of contractility a re due to altered Ca2+ handling, but no measurements of cytosolic Ca2 ([Ca2+](c)) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced change s in contractility are due to altered Ca2+ handling by measuring [Ca2](c) (indo 1) in hearts from rats drinking 36% ethanol for 7 mo and ag e-matched controls. Peak left ventricular pressure was depressed (-16% ), whereas rates of contraction (12%) and relaxation (14-20%) were fas ter in alcohol-exposed hearts. Systolic [Ca2+](c) (808 +/- 45 vs. 813 +/- 45 nM), diastolic [Ca2+](c) (195 +/- 11 vs. 193 +/- 10 nM), and ra tes of [Ca2+](c) rise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca2+ handling proteins, sarcoplasmi c reticulum Ca2+-ATPase and phospholamban, were the same in myocytes i solated from alcohol-exposed and control hearts (SDS-polyacrylamide ge l). These data suggest that chronic alcohol-induced contractile change s are not due to altered Ca2+ handling but may be due to changes at th e level of the myofilament. As a first step in elucidating the mechani sm(s) of alcohol-induced changes at the myofilament, we assessed myosi n heavy chain (MHC) isoform content (SDS-polyacrylamide gel). alpha-MH C was decreased relative to beta-MHC (a/a + b = 0.55 0.03 vs. 0.66 +/- 0.02; P < 0.02) in alcohol-exposed hearts, which cannot account for t he observed alcohol-induced contractile changes. In conclusion, change s of myocardial contractility due to chronic alcohol exposure do not r esult from altered Ca2+ handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.