Summary
Male Wistar rats were fed with ethanol for 33 weeks. Ethanol was administered in a liquid diet containing 33% of the calories as ethanol. In the control group ethanol was isocalorically replaced by glucose. Light and electron microscopic investigation of the hearts did not indicate significant structural abnormalities, in contrast to the results of some other groups. Nevertheless, morphometric analysis revealed considerable quantitative changes. The number of mitochondria was remarkably reduced and the volume of an average single mitochondrion nearly doubled, whereas the volume fractions of mitochondria and myofibrils were unaltered. The analysis of the mitochondrial subcompartments indicated a slight decrease of the surface area of inner mitochondrial membranes per unit volume of mitochondria and a slight increase of the volume fraction of the mitochondrial matrix space. Myocardial cell hypertrophy or atrophy were not observed. We believe that the mitochondrial changes are the expression of an impaired biogenesis of these organelles.
The increased number of capillaries in the ethanol-fed group is possibly caused by functional ethanol effects which may be partly similar to effects of chronic hypoxia.
Ethanol- or acetaldehyde-induced damage of heart mitochondria may play an important role in the pathogenesis of alcoholic cardiomyopathy.
Similar content being viewed by others
References
Ahmed S, Levinson GE, Regan TJ (1973) Depression of myocardial contractility with low doses of ethanol in normal man. Circulation 48:378–385
Albring M, Radsak K, Thoenes W (1975) Chloramphenicol-induced giant hepatic mitochondria. Naturwissenschaften 62:43–44
Alexander CS, Forsyth GW, Nagasawa HT, Kohlhoff JG (1977) Alcoholic cardiomyopathy in mice. Myocardial glycogen, lipids and certain enzymes. J Mol Cell Cardiol 9:235–245
Alexander CS, Sekhri KK, Nagasawa HT (1977) Alcoholic cardiomyopathy in mice. Electron microscopic observations. J Mol Cell Cardiol 9:247–254
Anversa P, Loud AV, Giacomelli F, Wiener J (1978) Absolute morphometric study of myocardial hypertrophy in experimental hypertension. II. Ultrastructure of myocytes and interstitium. Lab Invest 38:597–609
Bing RJ, Tillmanns H, Fauvel JM, Seeler K, Mao JC (1974) Effects of prolonged alcohol administration on calcium transport in heart muscle of the dog. Circ Res 35:33–38
Bing RJ (1978) Cardiac metabolism: Its contributions to alcoholic heart disease and myocardial failure. Circulation 58:965–970
Bulloch RT, Pearce MB, Murphy ML, Jenkins BJ, Davies JL (1972) Myocardial lesions in idiopathic and alcoholic cardiomyopathy. Am J Cardiol 29:15–25
Burch GE, Colcolough HL, Harb JM, Ching Ya Tsui (1971) The effect of ingestion of ethyl alcohol, wine and beer on the myocardium of mice. Am J Cardiol 27:522–528
Burke JP, Rubin E (1979) The effects of ethanol and acetaldehyde on the products of protein synthesis by liver mitochondria. Lab Invest 41:393–400
Cederbaum AI, Lieber CS, Rubin E (1974) Effects of chronic ethanol treatment on mitochondrial functions — Damage to coupling site I. Arch Biochem Biophys 165:560–569
Cederbaum AI, Rubin E (1975) Molecular injury to mitochondria produced by ethanol and acetaldehyde. Fed Proc 34:2045–2051
Child JS, Kovick RB, Levisman JA, Pearce ML (1979) Cardiac effects of acute ethanol ingestion unmasked by autonomic blockade. Circulation 59:120–125
DeHoff RT, Rhines FN (1961) Determination of number of particles per unit volume from measurements made on random plane sections: the general cylinder and the ellipsoid. Trans Metallurg Soc Am Inst Mining, Metallurgical and Petroleum Engineers 221:975–982
Demakis JG, Proskey A, Rahimtoola SH, Jamil M, Sutton GC, Rosen KM, Gunnar RM, Tobin JR (1974) The natural course of alcoholic cardiomyopathy. Ann Int Med 80:293–297
Doerr W, Rossner JA (1977) Toxische Arzneimittelwirkungen am Herzmuskel. Cardiovasculäre Therapie aus der Sicht der pathologischen Anatomie. Sitzungsberichte der Heidelberger Akademie der Wissenschaften Mathematisch-naturwissenschaftliche Klasse Jahrgang 1977, 4. Abhandlung. Springer, Berlin-Heidelberg-New York
Eliaser M, Giansiracusa FJ (1956) The heart and alcohol. Calif Med 84:234–236
Ettinger PO, Lyons M, Oldewurtel HA, Regan TJ (1976) Cardiac conduction abnormalities produced by chronic alcoholism. Am Heart J 91:66–78
Fahimi HD, Kino M, Hicks L, Thorp KA, Abelman WH (1979) Increased myocardial catalase in rats fed ethanol. Am J Pathol 96:373–390
Forsyth GW, Nagasawa HT, Alexander CS (1973) Acetaldehyde metabolism by the rat heart. Proc Soc Exp Biol Med 144:498–500
Forsyth GW, Nagasawa HT, Alexander CS (1976) Ethanol metabolism by the rat heart and alcohol dehydrogenase activity. Can J Biochem 54:539–545
French SW (1979) Role of mitochondrial damage in alcoholic liver disease. Biochemistry and pharmacology of ethanol, vol 1. In: Majchrowicz E, Noble EP (eds) Plenum Press, New York and London, p 409–444
Friedman I, Moravec J, Reichard E, Halt PY (1973) Subacute myocardial hypoxia in the rat. An electron microscopic study of the left ventricular myocardium. J Mol Cell Cardiol 5:125–132
Gvozdják A, Borovič F, Bada V, Kruty F, Niederland TR, Gvozdiák J (1976) Myocardial cell damage due to ethanol. In: Harris P, Bing RJ, Fleckenstein A (eds) Recent advances in studies on cardiac structure and metabolism, vol 7, University Park Press, Baltimore p 451–457
Hall JL, Rowlands DT (1970) Cardiotoxicity of alcohol. Am J Pathol 60:153–164
Hibbs RG, Ferrans VJ, Black WC, Weilbaecher DG, Walsh JJ, Burch GE (1965) Alcoholic cardiomyopathy. An electron microscopic study. Am Heart J 69:766–779
Hirota Y, Bing OHL, Abelmann WH (1976) Effect of ethanol on contraction and relaxation of isolated rat ventricular muscle. J Mol Cell Cardiol 8:727–732
Horwitz LD, Atkins JM (1974) Acute effects of ethanol on left ventricular performance. Circulation 49:124–128
Kiessling KH (1968) Effect of ethanol on rat liver. VI: A possible correlation between alphaglycerophophosphate oxidase activity and mitochondrial size in male and female rats fed ethanol. Acta Pharmacol Toxicol 26:245–252
Kiessling KH, Pilström L (1971) Ethanol and the human liver. Structural and metabolic changes in liver mitochondria. Cytobiologie 4:339–348
Klein H, Harmjanz D (1975) Effect of ethanol infusion on the ultrastructure of human myocardium. Postgrad Med J 51:325–329
Koch OR, Conti LLR, Bolanos LP, Soppani AOM (1978) Ultrastructural and biochemical aspects of liver mitochondria during recovery from ethanol-induced alterations. Experimental evidence of mitochondrial division. Am J Pathol 90:325–344
Kübler W, Zebc H, Mäurer W, Mehmel H, Zekl G (1976) Die kongestive Kardiomyopathie. Münchner Med Wochenschr 118:751–758
Kuhn H, Loogen F (1978) Die Wirkung von Alkohol auf das Herz einschließlich der Alkoholkardiomyopathie. Internist 19:97–106
Lacerda PR, Knieriem HJ, Bózner A (1969) Die Ultrastruktur des Herzmuskels der Ratte nach akuter Alkoholintoxikation. Z Kreislaufforsch 58:97–103
Lieber CS, Jones DP, DeCarli LM (1965) Effects of prolonged ethanol intake: Production of fatty liver despite adequate diets. J Clin Invest 44:1009–1021
Mall G, Kayser K, Rossner JA (1977) The loss of membrane images from oblique sectioning of biological membranes and the availability of morphometric principles — demonstrated by the examination of heart muscle mitochondria. Mikroskopie 33:246–254
Mall G, Reinhard H, Kayser K, Rossner JA (1978) An effective morphometric method for electron microscopic studies on papillary muscles. Virchows Arch. A Path Anat and Histol 379:219–228
Mall G, Reinhard H, Stopp D, Rossner JA (1980) Morphometric observations on the rat heart after high-dose treatment with cortisol. Virchows Arch A Path Anat and Histol 385:169–180
McCallister LP, Page E (1973) Effects of thyroxin on ultrastructure of rat myocardial cells: a stereological study. J Ultrastruct Res 42:136–155
Mösslacher H, Slany J, Hanak H, Stockinger L (1971) Alkoholkardiomyopathie. Z Kreislaufforsch 60:303–309
Neville JN, Eagles JA, Samson G, Olson RE (1968) Nutritional status of alcoholics. Am J Clin Nutr 21:1329–1340
Newman WH, Valicenti JF, Jr (1971) Ventricular function following acute alcohol administration: A strain-gauge analysis of depressed ventricular dynamics. Am Heart J 81:61–68
Pachinger OM, Tillmanns H, Mao JC, Fauvel JM, Bing RJ (1973) The effect of prolonged administration of ethanol on cardiac metabolism and performance in the dog. J Clin Invest 52:2690–2696
Porta EA, Koch OR, Gomez-Dumm CLA, Hartroft WS (1968) Effects of dietary protein on the liver of rats in experimental chronic alcoholism. J Nutr 94:437–446
Rawat AK (1979) Inhibition of cardiac protein synthesis by prolonged ethanol administration. Res Commun Chem Pathol Pharmacol 25:89–102
Regan TJ, Khan MI, Ettinger PO, Haider B, Lyons MM, Oldewurtel HA, Weber M (1974) Myocardial function and lipid metabolism in the chronic alcoholic animal. J Clin Invest 54:740–752
Reith A, Fuchs S (1973) The heart muscle of the rat under influence of triiodothyronine and riboflavin deficiency with special reference to mitochondria. Lab Invest 29:229–235
Reith A (1977) Probleme bei der Bestimmung von Oberflächendichten (OD) von Biomembranen. Mikroskopie 33:80–87
Retig JN, Kirchberger MA, Rubin E, Katz AM (1977) Effect of ethanol on calcium transport by microsomes phosphorylated by cyclic AMP-dependent protein kinase. Biochem Pharmacol 26:393–396
Rohr HP, Riede UN (1973) Experimental metabolic disorders and the subcellular reaction pattern (Morphometric analysis of hepatocyte mitochondria). In: Current Topics in Pathology, vol 58. Springer, Berlin-Heidelberg-New York, p 1–47
Rossi MA, Oliveira JSM, Zucoloto S, Becker PFL (1976) Norepinephrine levels and morphologic alterations of myocardium in chronic alcoholic rats. Beitr Pathol 159:51–60
Rubin E, Beattie DS, Lieber CS (1970) Effects of ethanol on the biogenesis of mitochondrial membranes and associated mitochondrial functions. Lab Invest 23:620–627
Sarma JSM, Ikeda S, Fischer R, Maruyama Y, Weishaar R, Bing RJ (1976) Biochemical and contractile properties of heart muscle after prolonged alcohol administration. J Mol Cell Cardiol 8:951–972
Schreiber SS, Briden K, Oratz M, Rothschild MA (1972) Ethanol, acetaldehyde, and myocardial protein synthesis. J Clin Invest 51:2820–2826
Schreiber SS, Oratz M, Rothschild MA, Reff F, Evans C (1974) Alcoholic cardiomyopathy. II The inhibition of cardiac microsomal protein synthesis by acetaldehyde. J Mol Cell Cardiol 6:207–213
Schwartz L, Sample KA, Wigle ED (1975) Severe alcoholic cardiomyopathy reversed with abstention from alcohol. Am J Cardiol 36:963–966
Segel LD, v. Rendig S, Choquet Y, Chacko K, Amsterdam EA, Mason DT (1975) Effects of chronic graded ethanol consumption on the metabolism, ultrastructure, and mechanical function of the rat heart. Cardiovasc Res 9:649–663
Segel LD, Mason DT (1979) Acute effects of acetaldehyde and ethanol on rat heart mitochondria. Res Commun Chem Pathol Pharmacol 25:461–474
Sitte H (1967) Morphometrische Untersuchungen an Zellen. In: Weibel ER. Elias H (eds) Symposionüber quantitative Methoden in der Morphologie, Wiesbaden 1965. Springer, Berlin-Heidelberg-New York, p 167
Smith HE, Page E (1976) Morphometry of rat mitochondrial subcompartments and membranes: application to myocardial cell atrophy after hypophysectomy. J Ultrastruct Res 55:31–41
Sohal RS, Burch GE (1969) Effects of alcohol ingestion on the intercalated disc in the mouse heart. Experientia 25:279–280
Vodovar N, Desnoyers F (1975) Influence du mode de fixation sur la morphologie ultrastructurale des cellules normales et altérées du myocarde. J Microscopie Biol Cell 24:239–248
Volk B, Mall G, Mattfeldt T (1979) The effect of chronic ethanol application on the rat hypothalamus and cerebellum. Light and electron microscopic investigations. Intern Congr Neurotoxicol Meet Ital Society Toxicol, Varese 27–30 September, 1979, Abstracts p 208
Weibel ER (1969) Stereological principles for morphometry in electron microscopic cytology. Int Rev Cytol 26:235–302
Weiss S, Wilkins RW (1937) The nature of the cardiovascular disturbances in the nutritional deficiency states (Beriberi). Ann Intern Med 11:104–148
Williams ES, Ting-Kai Li (1977) The effect of chronic alcohol administration on fatty acid metabolism and pyruvate oxidation of heart mitochondria. J Mol Cell Cardiol 9:1003–1011
Wong M (1973) Depression of cardiac performance by ethanol unmasked during autonomic blockade. Am Heart J 86:508–515
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. Dr. G. Ule on the occasion of his 60th birthday
More detailed discussion in T. Mattfeldt: Inauguraldissertation (in prep.)
Supported by grants of the Deutsche Forschungsgemeinschaft VO 272/3
Rights and permissions
About this article
Cite this article
Mall, G., Mattfeldt, T. & Volk, B. Ultrastructural morphometric study on the rat heart after chronic ethanol feeding. Virchows Arch. A Path. Anat. and Histol. 389, 59–77 (1980). https://doi.org/10.1007/BF00428668
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00428668