INFLUENCE OF NICOTINE ON MYOCARDIAL STIFFNESS AND FIBROSIS DURING CHRONIC ETHANOL USE

Cardiomyopathy related to ethanol abuse is often accompanied by cigare tte use. To examine if the major cardioactive component may intensify the abnormal function acid composition induced by chronic ethanol, nic otine was administered orally, 2.5 mg bid, to a canine model receiving 38% of calories as ethanol for 6 months (group III), These animals we re compared with group II receiving ethanol alone, group IV on nicotin e alone, and controls (group I), In the intact, ventilated, anesthetiz ed dog, left ventricular pressures and volumes were measured before an d after dextran infusion and related to left ventricular collagen alte rations, Basal heart rate, aortic pressure, and ejection fraction were comparable with controls. End-diastolic pressure and diastolic chambe r stiffness (KPV) were significantly higher in the basal state and dur ing dextran infusion in the three experimental groups, compared with g roup I, The increment was largest in the ethanol-nicotine group. Analy sis of left ventricular myocardium revealed a rise of collagen concent rations in all three experimental groups, with an interstitial distrib ution on histochemical examination, Moreover, determination of advance d glycosylation endproducts, as a measure of alterations in collagen c ross-links, revealed higher concentrations versus controls, The greate r increase of diastolic stiffness in the nicotine-ethanol group occurr ed despite a similar concentration of fluorescent products as group II . Because the former had a larger increase of collagen concentration, total cross-linked collagen content was presumably greater after the c ombined use of nicotine-ethanol. Thus, nicotine in relatively high dos e when combined with ethanol, elicited a modest further increase in th e left ventricular chamber stiffness and collagen concentration.