Influence of nicotine on myocardial stiffness and fibrosis during chronic ethanol use.
Cardiomyopathy related to ethanol abuse is often accompanied by cigarette use. To examine if the major cardioactive component may intensify the abnormal function and composition induced by chronic ethanol, nicotine was administered orally, 2.5 mg bid, to a canine model receiving 36% of calories as ethanol for 6 months (group III). These animals were compared with group II receiving ethanol alone, group IV on nicotine alone, and controls (group I). In the intact, ventilated, anesthetized dog, left ventricular pressures and volumes were measured before and after dextran infusion and related to left ventricular collagen alterations. Basal heart rate, aortic pressure, and ejection fraction were comparable with controls. End-diastolic pressure and diastolic chamber stiffness (KPV) were significantly higher in the basal state and during dextran infusion in the three experimental groups, compared with group I. The increment was largest in the ethanol-nicotine group. Analysis of left ventricular myocardium revealed a rise of collagen concentrations in all three experimental groups, with an interstitial distribution on histochemical examination. Moreover, determination of advanced glycosylation endproducts, as a measure of alterations in collagen cross-links, revealed higher concentrations versus controls. The greater increase of diastolic stiffness in the nicotine-ethanol group occurred despite a similar concentration of fluorescent products as group II. Because the former had a larger increase of collage concentration, total cross-linked collagen content was presumably greater after the combined use of nicotine-ethanol. Thus, nicotine in relatively high dose when combined with ethanol, elicited a modest further increase in the left ventricular chamber stiffness and collagen concentration.
Department of Medicine, UMDNJ--New Jersey Medical School, Newark 07103-2714, USA.
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Rajiyah
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Agarwal
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Avendano
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Lyons
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Soni
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TJ
Regan
D000284:Administration, Oral; D000818:Animals; D001696:Biomechanical Phenomena; D001786:Blood Glucose / Q000378:metabolism; D002310:Cardiomyopathy, Alcoholic / Q000473:pathology / Q000503:physiopathology*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D009538:Nicotine / Q000494:pharmacology*; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D003094:Collagen; D006442:Glycated Hemoglobin; D009538:Nicotine