Journal of Biomedical Science | |
Slow conduction and gap junction remodeling in murine ventricle after chronic alcohol ingestion | |
Hung-I Yeh3  Cheng-Ho Tsai3  Yu-Shien Ko2  Cheng-I Lin1  Ya-Ming Tseng3  Ray-Ching Hong3  Chung-Lieh Hung3  Yu-Jun Lai3  | |
[1] Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan;The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan;Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Mackay Medical College, New Taipei City, Taiwan | |
关键词: optical mapping; gap junctions; remodeling; arrhythmia; alcohol; | |
Others : 829241 DOI : 10.1186/1423-0127-18-72 |
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received in 2011-07-11, accepted in 2011-09-29, 发布年份 2011 | |
【 摘 要 】
Background
Long-term heavy alcohol drinkers are prone to the development of cardiac arrhythmia. To understand the mechanisms, we evaluated the cardiac structural and electrophysiological changes in mice chronically drinking excessive alcohol.
Results
Male C57BL/6J mice were given 36% alcohol in the drinking water. Those given blank water were used as control. Twelve weeks later, the phenotypic characteristics of the heart, including gap junctions and electrical properties were examined. In the alcohol group the ventricles contained a smaller size of cardiomyocytes and a higher density of capillary networks, compared to the control. Western blots showed that, after drinking alcohol, the content of connexin43 (Cx43) protein in the left ventricle was increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated that Cx43 gap junctions were up-regulated in the alcohol group with a disorganized distribution, compared to the control. Optical mapping showed that the alcohol group had a reduced conduction velocity (40 ± 18 vs 60 ± 7 cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs 30%, p < 0.05).
Conclusion
Long-term excessive alcohol intake resulted in extensive cardiac remodeling, including changes in expression and distribution of gap junctions, growth of capillary network, reduction of cardiomyocyte size, and decrease of myocardial conduction.
【 授权许可】
2011 Lai et al; licensee BioMed Central Ltd.
【 预 览 】
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20140714061341686.pdf | 1101KB | download | |
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Figure 4. | 135KB | Image | download |
Figure 3. | 30KB | Image | download |
Figure 2. | 73KB | Image | download |
Figure 1. | 77KB | Image | download |
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【 参考文献 】
- [1]Lang CH, Frost RA, Summer AD, Vary TC: Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart. Int J Biochem Cell Biol 2005, 37:2180-2195.
- [2]Lee WK, Regan TJ: Alcoholic cardiomyopathy: is it dose-dependent? Congest Heart Fail 2002, 8:303-306.
- [3]Patel VB, Why HJ, Richardson PJ, Preedy VR: The effects of alcohol on the heart. Adverse Drug React Toxicol Rev 1997, 16:15-43.
- [4]Iacovoni A, De Maria R, Gavazzi A: Alcoholic cardiomyopathy. J Cardiovasc Med (Hagerstown) 2010, 11:884-892.
- [5]Goodkind MJ, Gerber NH, Mellen JR, Kostis JB: Altered intracardiac conduction after acute administration of ethanol in the dog. J Pharmacol Exp Ther 1975, 194:633-638.
- [6]Kupari M, Koskinen P: Alcohol, cardiac arrhythmias and sudden death. Novartis Found Symp 1998, 216:68-79. discussion 79-85
- [7]Williams ES, Mirro MJ, Bailey JC: Electrophysiological effects of ethanol, acetaldehyde, and acetate on cardiac tissues from dog and guinea pig. Circ Res 1980, 47:473-478.
- [8]Gros DB, Jongsma HJ: Connexins in mammalian heart function. Bioessays 1996, 18:719-730.
- [9]Severs NJ, Coppen SR, Dupont E, Yeh HI, Ko YS, Matsushita T: Gap junction alterations in human cardiac disease. Cardiovasc Res 2004, 62:368-377.
- [10]Gutstein DE, Morley GE, Vaidya D, Liu F, Chen FL, Stuhlmann H, Fishman GI: Heterogeneous expression of Gap junction channels in the heart leads to conduction defects and ventricular dysfunction. Circulation 2001, 104:1194-1199.
- [11]Lerner DL, Yamada KA, Schuessler RB, Saffitz JE: Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in Cx43-deficient mice. Circulation 2000, 101:547-552.
- [12]Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC: Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav 2005, 84:53-63.
- [13]Piano MR: Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest 2002, 121:1638-1650.
- [14]Kupari M, Koskinen P, Suokas A: Left ventricular size, mass and function in relation to the duration and quantity of heavy drinking in alcoholics. Am J Cardiol 1991, 67:274-279.
- [15]Lazarevic AM, Nakatani S, Neskovic AN, Marinkovic J, Yasumura Y, Stojicic D, Miyatake K, Bojic M, Popovic AD: Early changes in left ventricular function in chronic asymptomatic alcoholics: relation to the duration of heavy drinking. J Am Coll Cardiol 2000, 35:1599-1606.
- [16]Urbano-Marquez A, Fernandez-Sola J: Alcohol consumption and heart failure. J Card Fail 2005, 11:329-332.
- [17]Urbano-Marquez A, Estruch R, Navarro-Lopez F, Grau JM, Mont L, Rubin E: The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med 1989, 320:409-415.
- [18]Wang L, Zhou Z, Saari JT, Kang YJ: Alcohol-induced myocardial fibrosis in metallothionein-null mice: prevention by zinc supplementation. Am J Pathol 2005, 167:337-344.
- [19]Preedy VR, Reilly ME, Patel VB, Richardson PJ, Peters TJ: Protein metabolism in alcoholism: effects on specific tissues and the whole body. Nutrition 1999, 15:604-608.
- [20]Mall G, Mattfeldt T, Rieger P, Volk B, Frolov VA: Morphometric analysis of the rabbit myocardium after chronic ethanol feeding-early capillary changes. Basic Res Cardiol 1982, 77:57-67.
- [21]Vikhert AM, Tsiplenkova VG, Cherpachenko NM: Alcoholic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol 1986, 8:3A-11A.
- [22]Gu JW, Elam J, Sartin A, Li W, Roach R, Adair TH: Moderate levels of ethanol induce expression of vascular endothelial growth factor and stimulate angiogenesis. Am J Physiol Regul Integr Comp Physiol 2001, 281:R365-372.
- [23]Jankala H, Eriksson PC, Eklund K, Sarviharju M, Harkonen M, Maki T: Effect of chronic ethanol ingestion and gender on heart left ventricular p53 gene expression. Alcohol Clin Exp Res 2005, 29:1368-1373.
- [24]Teodoro JG, Evans SK, Green MR: Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. J Mol Med 2007, 85:1175-1186.
- [25]Spach MS, Starmer CF: Altering the topology of gap junctions a major therapeutic target for atrial fibrillation. Cardiovasc Res 1995, 30:337-344.
- [26]Saffitz JE, Davis LM, Darrow BJ, Kanter HL, Laing JG, Beyer EC: The molecular basis of anisotropy: role of gap junctions. J Cardiovasc Electrophysiol 1995, 6:498-510.
- [27]Spach MS, Heidlage JF, Dolber PC, Barr RC: Electrophysiological effects of remodeling cardiac gap junctions and cell size: experimental and model studies of normal cardiac growth. Circulation Research 2000, 86:302-311.
- [28]Yeh HI, Lai YJ, Lee YN, Chen YJ, Chen YC, Chen CC, Chen SA, Lin CI, Tsai CH: Differential expression of connexin43 gap junctions in cardiomyocytes isolated from canine thoracic veins. J Histochem Cytochem 2003, 51:259-266.
- [29]Jacobi J, Tam BY, Wu G, Hoffman J, Cooke JP, Kuo CJ: Adenoviral gene transfer with soluble vascular endothelial growth factor receptors impairs angiogenesis and perfusion in a murine model of hindlimb ischemia. Circulation 2004, 110:2424-2429.