Diabetes enhances acetaldehyde-induced depression of cardiac myocyte contraction

It is well established that cardiomyopathy is a consistent feature of diabe tes and that alcohol consumption increases the risk of cardiovascular disea se among diabetic subjects. Acetaldehyde (ACA), the main ethanol metabolite , is considered to play a role in the ethanol-induced cardiac dysfunction, It has been reported recently that the negative inotropic effect of ACA was more potent in the diabetic myocardium, To determine whether the disparate ACA-induced myocardial depression in diabetes is due to intrinsic alterati ons at the cellular level, mechanical properties in response to ACA were ev aluated in ventricular myocytes from both normal and streptozotocin-induced diabetic rat hearts. Myocytes were electrically stimulated to contract at 0.5 Hz and contractile properties analyzed included peak shortening (PS), t ime-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening and relengthening (+/-dL/dt). Ca2+ transients were measured as fura-2 fluorescence intensity (Delta FFI) changes. ACA (0.1-30 mM) dispropo rtionately depressed PS in a dose-dependent manner, in myocytes from diabet ic hearts compared to normal hearts, Interestingly, the degree of inhibitio n in Delta FFI was similar in both groups. Neither the duration nor maximal velocities of shortening and relengthening were affected by ACA in either group, These results are the first to suggest that enhanced ACA-induced myo cardial depression in diabetes is due to disparate intrinsic actions on ind ividual myocytes, The mechanism underlying the alteration of ACA-induced my ocardial depression may be due, in part, to depressed Ca2+ responsiveness i n diabetic hearts. (C) 2000 academic Press.