Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Sep;54(3):740–752. doi: 10.1172/JCI107812

Myocardial Function and Lipid Metabolism in the Chronic Alcoholic Animal

Timothy J Regan 1, Mohammad I Khan 1, Philip O Ettinger 1, Bunyad Haider 1, Michael M Lyons 1, Henry A Oldewurtel 1, Marilyn Weber 1
PMCID: PMC301608  PMID: 4368946

Abstract

In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium.

To evaluate myocardial lipid metabolism, [1-14C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced 14CO2 production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [14C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.

Full text

PDF
750

Images in this article

746Image
on p.746

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander C. S. Idiopathic heart disease. II. Electron microscopic examination of myocardial biopsy specimens in alcoholic heart disease. Am J Med. 1966 Aug;41(2):229–234. doi: 10.1016/0002-9343(66)90018-0. [DOI] [PubMed] [Google Scholar]
  2. Asokan S. K., Frank M. J., Witham A. C. Cardiomyopathy without cardiomegaly in alcoholics. Am Heart J. 1972 Jul;84(1):13–18. doi: 10.1016/0002-8703(72)90300-6. [DOI] [PubMed] [Google Scholar]
  3. Auger C., Chenard J. Quebec beer-drinkers' cardiomyopathy: ultrastructural changes in one case. Can Med Assoc J. 1967 Oct 7;97(15):916–921. [PMC free article] [PubMed] [Google Scholar]
  4. BRIGDEN W. CARDIAC AMYLOIDOSIS. Prog Cardiovasc Dis. 1964 Sep;7:142–150. doi: 10.1016/s0033-0620(64)80016-5. [DOI] [PubMed] [Google Scholar]
  5. Brady A. J. Active state in cardiac muscle. Physiol Rev. 1968 Jul;48(3):570–600. doi: 10.1152/physrev.1968.48.3.570. [DOI] [PubMed] [Google Scholar]
  6. Buja L. M., Khoi N. B., Roberts W. C. Clinically significant cardiac amyloidosis. Clinicopathologic findings in 15 patients. Am J Cardiol. 1970 Oct;26(4):394–405. doi: 10.1016/0002-9149(70)90736-8. [DOI] [PubMed] [Google Scholar]
  7. Bulloch R. T., Pearce M. B., Murphy M. L., Jenkins B. J., Davis J. L. Myocardial lesions in idiopathic and alcoholic cardiomyopathy. Study by ventricular septal biopsy. Am J Cardiol. 1972 Jan;29(1):15–25. doi: 10.1016/0002-9149(72)90410-9. [DOI] [PubMed] [Google Scholar]
  8. Carleton R. A., Bowyer A. F., Graettinger J. S. Overestimation of left ventricular volume by the indicator dilution technique. Circ Res. 1966 Mar;18(3):248–256. doi: 10.1161/01.res.18.3.248. [DOI] [PubMed] [Google Scholar]
  9. FAILING J. F., Jr, BUCKLEY M. W., ZAK B. Automatic determination of serum proteins. Tech Bull Regist Med Technol. 1959 Dec;29:205–210. [PubMed] [Google Scholar]
  10. FERRANS V. J., HIBBS R. G., WEILBAECHER D. G., BLACK W. C., WALSH J. J., BURCH G. E. ALCOHOLIC CARDIOMYOPATHY; A HISTOCHEMICAL STUDY. Am Heart J. 1965 Jun;69:748–765. doi: 10.1016/0002-8703(65)90449-7. [DOI] [PubMed] [Google Scholar]
  11. Ferrans V. J. Alcoholic cardiomyopathy. Am J Med Sci. 1966 Jul;252(1):89–104. doi: 10.1097/00000441-196607000-00014. [DOI] [PubMed] [Google Scholar]
  12. Ferrans V. J., Roberts W. C., Shugoll G. I., Massumi R. A., Ali N. Plasma membrane extensions in intercalated discs of human myocardium and their relationship to partial dissociations of the discs. J Mol Cell Cardiol. 1973 Apr;5(2):161–169. doi: 10.1016/0022-2828(73)90049-7. [DOI] [PubMed] [Google Scholar]
  13. Frank M. J., Cundey P. E., Jr, Crews T. L., Lewis W. J., 3rd Comparison of left ventricular volumes by single-plane cineangiography and by indicator dilution. J Lab Clin Med. 1971 Apr;77(4):580–593. [PubMed] [Google Scholar]
  14. Frank M. J., Levinson G. E. An index of the contractile state of the myocardium in man. J Clin Invest. 1968 Jul;47(7):1615–1626. doi: 10.1172/JCI105853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Frank M. J., Nadimi M., Casanegra P., Stein P., Pekaar R. Effect of angiotensin on myocardial function. Am J Physiol. 1970 May;218(5):1267–1272. doi: 10.1152/ajplegacy.1970.218.5.1267. [DOI] [PubMed] [Google Scholar]
  16. Gloster J., Harris P. Effect of anaerobiosis on the incorporation of ( 14 C)acetate into lipid in the perfused rat heart. J Mol Cell Cardiol. 1972 Jun;4(3):213–228. doi: 10.1016/0022-2828(72)90059-4. [DOI] [PubMed] [Google Scholar]
  17. Gould L., Shariff M., Zahir M., Di Lieto M. Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop. J Clin Invest. 1969 May;48(5):860–868. doi: 10.1172/JCI106044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gvozdják A., Bada V., Krutý F., Niederland T. R., Gvozdják J. Chronic effect of ethanol on the metabolism of myocardium. Biochem Pharmacol. 1973 Jul 15;22(14):1807–1811. doi: 10.1016/0006-2952(73)90395-x. [DOI] [PubMed] [Google Scholar]
  19. HIBBS R. G., FERRANS V. J., BLACK W. C., WEILBAECHER D. G., BURCH G. E. ALCOHOLIC CARDIOMYOPATHY; AN ELECTRON MICROSCOPIC STUDY. Am Heart J. 1965 Jun;69:766–779. doi: 10.1016/0002-8703(65)90450-3. [DOI] [PubMed] [Google Scholar]
  20. HILL J. B., KESSLER G. An automated determination of glucose utilizing a glucose oxidase-peroxidase system. J Lab Clin Med. 1961 Jun;57:970–980. [PubMed] [Google Scholar]
  21. Hall J. L., Rowlands D. T., Jr Cardiotoxicity of alcohol. An electron microscopic study in the rat. Am J Pathol. 1970 Aug;60(2):153–164. [PMC free article] [PubMed] [Google Scholar]
  22. Harman M. A., Markov A., Lehan P. H., Oldewurtel H. A., Regan T. J. Coronary blood flow measurements in the presence of arterial obstruction. Circ Res. 1966 Sep;19(3):632–637. doi: 10.1161/01.res.19.3.632. [DOI] [PubMed] [Google Scholar]
  23. Holt J. P., Rhode E. A., Kines H. Ventricular volumes and body weight in mammals. Am J Physiol. 1968 Sep;215(3):704–715. doi: 10.1152/ajplegacy.1968.215.3.704. [DOI] [PubMed] [Google Scholar]
  24. Hugenholtz P. G., Wagner H. R., Sandler H. The in vivo determination of left ventricular volume. Comparison of the fiberoptic-indicator dilution and the angiocardiographic methods. Circulation. 1968 Apr;37(4):489–508. doi: 10.1161/01.cir.37.4.489. [DOI] [PubMed] [Google Scholar]
  25. Joly J. G., Feinman L., Ishii H., Lieber C. S. Effect of chronic ethanol feeding on hepatic microsomal glycerophosphate acyltransferase activity. J Lipid Res. 1973 May;14(3):337–343. [PubMed] [Google Scholar]
  26. KELLEY T. F. IMPROVED METHOD FOR MICROTITRATION OF FATTY ACIDS. Anal Chem. 1965 Jul;37:1078–1079. doi: 10.1021/ac60227a044. [DOI] [PubMed] [Google Scholar]
  27. Keroes J., Rapaport E. Ventricular volume measurement in the awake dog using implanted thermistor beads. J Appl Physiol. 1972 Mar;32(3):404–408. doi: 10.1152/jappl.1972.32.3.404. [DOI] [PubMed] [Google Scholar]
  28. LEEVY C. M., BAKER H., TENHOVE W., FRANK O., CHERRICK G. R. B-COMPLEX VITAMINS IN LIVER DISEASE OF THE ALCOHOLIC. Am J Clin Nutr. 1965 Apr;16:339–346. doi: 10.1093/ajcn/16.4.339. [DOI] [PubMed] [Google Scholar]
  29. LEVINE J. B., ZAK B. AUTOMATED DETERMINATION OF SERUM TOTAL CHOLESTEROL. Clin Chim Acta. 1964 Oct;10:381–384. doi: 10.1016/0009-8981(64)90073-7. [DOI] [PubMed] [Google Scholar]
  30. Levinson G. E., Frank M. J., Nadimi M., Braunstein M. Studies of cardiopulmonary blood volume. Measurement of left ventricular volume by dye dilution. Circulation. 1967 Jun;35(6):1038–1048. doi: 10.1161/01.cir.35.6.1038. [DOI] [PubMed] [Google Scholar]
  31. Lochner A., Cowley R., Brink A. J. Effect of ethanol on metabolism and function of perfused rat heart. Am Heart J. 1969 Dec;78(6):770–780. doi: 10.1016/0002-8703(69)90443-8. [DOI] [PubMed] [Google Scholar]
  32. Maines J. E., 3rd, Aldinger E. E. Myocardial depression accompanying chronic consumption of alcohol. Am Heart J. 1967 Jan;73(1):55–63. doi: 10.1016/0002-8703(67)90309-2. [DOI] [PubMed] [Google Scholar]
  33. Maseri A., Enson Y. Mixing in the right ventricle and pulmonary artery in man: evaluation of ventricular volume measurements from indicator washout curves. J Clin Invest. 1968 Apr;47(4):848–859. doi: 10.1172/JCI105778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. NASH C. B., DAVIS F., WOODBURY R. A. Cardiovascular effects of anesthetic doses of pentobarbital sodium. Am J Physiol. 1956 Apr;185(1):107–112. doi: 10.1152/ajplegacy.1956.185.1.107. [DOI] [PubMed] [Google Scholar]
  35. NEWMAN E. V., MERRELL M., GENECIN A., MONGE C., MILNOR W. R., McKEEVER W. P. The dye dilution method for describing the central circulation. An analysis of factors shaping the time-concentration curves. Circulation. 1951 Nov;4(5):735–746. doi: 10.1161/01.cir.4.5.735. [DOI] [PubMed] [Google Scholar]
  36. Neely J. R., Rovetto M. J., Oram J. F. Myocardial utilization of carbohydrate and lipids. Prog Cardiovasc Dis. 1972 Nov-Dec;15(3):289–329. doi: 10.1016/0033-0620(72)90029-1. [DOI] [PubMed] [Google Scholar]
  37. Neville J. N., Eagles J. A., Samson G., Olson R. E. Nutritional status of alcoholics. Am J Clin Nutr. 1968 Nov;21(11):1329–1340. doi: 10.1093/ajcn/21.11.1329. [DOI] [PubMed] [Google Scholar]
  38. O'Rourke R. A., Pegram B., Bishop V. S. Variable effect of angiotensin infusion on left ventricular function. Cardiovasc Res. 1972 May;6(3):240–247. doi: 10.1093/cvr/6.3.240. [DOI] [PubMed] [Google Scholar]
  39. Pachinger O. M., Tillmanns H., Mao J. C., Fauvel J. M., Bing R. J. The effect of prolonged administration of ethanol on cardiac metabolism and performance in the dog. J Clin Invest. 1973 Nov;52(11):2690–2696. doi: 10.1172/JCI107463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. ROSS J., Jr, BRAUNWALD E. THE STUDY OF LEFT VENTRICULAR FUNCTION IN MAN BY INCREASING RESISTANCE TO VENTRICULAR EJECTION WITH ANGIOTENSIN. Circulation. 1964 May;29:739–749. doi: 10.1161/01.cir.29.5.739. [DOI] [PubMed] [Google Scholar]
  41. Regan T. J. Ethyl alcohol and the heart. Circulation. 1971 Nov;44(5):957–963. doi: 10.1161/01.cir.44.5.957. [DOI] [PubMed] [Google Scholar]
  42. Regan T. J., Khan M. I., Jesrani M. U., Oldewurtel H. A., Ettinger P. O. Alterations of myocardial function and metabolism in chronic diabetes mellitus. Recent Adv Stud Cardiac Struct Metab. 1973;3:169–178. [PubMed] [Google Scholar]
  43. Regan T. J., Levinson G. E., Oldewurtel H. A., Frank M. J., Weisse A. B., Moschos C. B. Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy. J Clin Invest. 1969 Feb;48(2):397–407. doi: 10.1172/JCI105997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Regan T. J., Markov A., Khan M. I., Jesrani M. U., Oldewurtel H. A., Ettinger P. O. Myocardial ion and lipid changes during ischemia and catecholamine induced necrosis: Relation to regional blood flow. Recent Adv Stud Cardiac Struct Metab. 1972;1:656–664. [PubMed] [Google Scholar]
  45. Regan T. J., Passannante A. J., Khan M. I., Oldewurtel H. A., Jesrani M. U. Influence of scar on left ventricular performance at the onset of myocardial ischemia: shock versus heart failure. J Clin Invest. 1971 Mar;50(3):534–542. doi: 10.1172/JCI106522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Regan T. J., Passannante A. J., Oldewurtel H. A., Burke W. M., Ettinger P. O. Cardiac metabolism of triglyceride, acetate, and oleate in early l-norepinephrine injury. J Appl Physiol. 1972 Sep;33(3):325–330. doi: 10.1152/jappl.1972.33.3.325. [DOI] [PubMed] [Google Scholar]
  47. Reitz R. C., Helsabeck E., Mason D. P. Effects of chronic alcohol ingestion on the fatty acid composition of the heart. Lipids. 1973 Feb;8(2):80–84. doi: 10.1007/BF02534333. [DOI] [PubMed] [Google Scholar]
  48. Roach M. K., Creaven P. J. A micro-method for the determination of acetaldehyde and ethanol in blood. Clin Chim Acta. 1968 Aug;21(2):275–278. doi: 10.1016/0009-8981(68)90138-1. [DOI] [PubMed] [Google Scholar]
  49. SWAN H. J., BECK W. Ventricular nonmixing as a source of error in the estimation of ventricular volume by the indicator-dilution technic. Circ Res. 1960 Sep;8:989–998. doi: 10.1161/01.res.8.5.989. [DOI] [PubMed] [Google Scholar]
  50. Schenk E. A., Cohen J. The heart in chronic alcoholism. Clinical and pathologic findings. Pathol Microbiol (Basel) 1970;35(1):96–104. doi: 10.1159/000162206. [DOI] [PubMed] [Google Scholar]
  51. Spodick D. H., Pigott V. M., Chirife R. Preclinical cardiac malfunction in chronic alcoholism. Comparison with matched normal controls and with alcoholic cardiomyopathy. N Engl J Med. 1972 Oct 5;287(14):677–680. doi: 10.1056/NEJM197210052871401. [DOI] [PubMed] [Google Scholar]
  52. Whereat A. F., Orishimo M. W. Effects of fasting and diabetes on fatty acid synthesis by heart mitochondria. Am J Physiol. 1969 Oct;217(4):998–1003. doi: 10.1152/ajplegacy.1969.217.4.998. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES