Influence of Nicotine on Myocardial Stiffness and Fibrosis During Chronic Ethanol Use

Abstract

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.

Increased Myostatin Activity and Decreased Myocyte Proliferation in Chronic Alcoholic Cardiomyopathy

“…With the design of this study, only a retrospective approach for the drinking habits of all donors by the family members was possible. Since alcoholic donors had significantly higher active smoking consumption compared to the other groups, we cannot exclude an additional noxious effect of nicotine in the myocardium as reported in experimental (Rajiyah et al, 1996) and clinical studies (Zakhari, 1991), although nicotine heart effect mainly induces coronary artery lesions. Evaluation of myocardial apoptosis is limited to TUNEL, BAX, and BCL-2 activities.…”

Alteration of the material properties of the normal supraspinatus tendon by nicotine treatment in a rat model

“…The increased elastic modulus due to nicotine might be related to increased synthesis of collagen or reduced production of matrix metalloproteinase. It has been reported that nicotine leads to increased collagen synthesis in beagles (Ahmed et al 1976) and that nicotine causes an increase in cross-linked collagen content, resulting in fibrosis of the myocardial interstitium in dogs (Rajiyah et al 1996). Thus, increased collagen synthesis or increased cross-linked collagen content of fibroblasts might induce increased elastic modulus due to nicotine administration in the tendon.…”

Effects of Metformin on Collagen Glycation and Diastolic Dysfunction in Diabetic Myocardium

“…Advanced glycosylation of collagen observed in this diabetic model is presumed to provide cross-links that confer enhanced stiffness to the protein, a process also observed in pathologic states in which nonglucose adducts are likely to be involved (29). Although characterized by fluorescence of collagen, other glycosylated products may be elicited by diabetes.…”