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Hamster Cardiomyopathy: A Genetically-Transmitted Sympathetic Dystrophy?

  • M. J. Sole
  • S. M. Factor
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 46)

Abstract

The cardiomyopathic Syrian hamster is a reproduceable paradigm of a genetically transmitted congestive cardiomyopathy. The cardiac disease first becomes manifest in juvenile hamsters (30–60 days old) with the development of patchy myocardial necrosis. Previous work has shown the myocardium of neonatal myopathic hamsters to be hypersensitive to the cardiotoxic effects of the catecholamines. Perfusion of hamster hearts, in vivo, with liquid silicone rubber has revealed numerous areas of microvascular constriction in the cardiomyopathy; both the microvascular alterations and the myocardial necrosis could be abolished by pretreating juvenile hamsters with verapamil. In this study we examine further the pathogenesis of the cardiomyopathy. Juvenile hamsters of various cardiomyopathic (Bio 14.6, 40.54, 53.58, 82.62) and control (Bio 2.4, 87.20, XXB, RB) strains were studied. Cardiac norepinephrine turnover in each of the cardiomyopathic strains was greater than that for any of the control strains (Range 119–223 ng/g/hr and 35–108 ng/g/hr respectively). The administration of prazosin an α1 antagonist for two weeks had a marked ameliorating effect (area of micronecrosis 8.8% in untreated vs 0.66% in treated). Thus hamster cardiomyopathy appears to depend on the genetic transmission of a hypersensitivity of both vascular smooth muscle cells and cardiac myocytes to catecholamine stimulation. With postnatal maturation of the sympathetic nervous system there is an increase in cardiac neural norepinephrine release which leads to microvascular spasm which in turn, by subjecting the hypersusceptible myocyte population to repeated episodes of ischemia and reperfusion, leads to myocyte loss and compensatory hypertrophy in the remaining myocardial cells. This process is obviated by calcium entry blockers or markedly ameliorated by α antagonists.

Keywords

Myocardial Necrosis Cardiac Sympathetic Nerve Normal Hamster Cardiomyopathic Hamster Norepinephrine Turnover 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Homburger F, Baker JR, Nixon CW, Whitney R: Primary generalized polymyopathy and cardiac necrosis in an inbred line of Syrian hamsters. Med Exp (6): 339–345, 1962.Google Scholar
  2. 2.
    Bishop SP, Sole MJ and Tilley LP: Cardiomypathies. In: Andrews EJ, Ward BC and Altman NH (eds) Spontaneous Models of Human Disease. Academic Press, New York, 1979, pp 59–64.Google Scholar
  3. 3.
    Bajusz E, Homburger F, Baker JR and Bogdonoff P: Dissociation of factors influencing myocardial degeneration and cirulatory failure. Ann N.Y. Acad Sci (156): 397–420, 1969.Google Scholar
  4. 4.
    Lossnitzer K, Janke J, Hein B, Stauch M, Fleckenstein A: Disturbed myocardial calcium metabolism: a possible pathogenetic factor in the hereditary cardiomyopathy of the Syrian hamster. In: Fleckenstein A, Rona G (eds) Recent advances in studies on cardiac structure and metabolism, vol 6: Pathophysiology and morphology of myocardial cell alteration. University Park Press, Baltimore, 1975, pp 207–217.Google Scholar
  5. 5.
    Strobeck JE, Factor SM, Bhan A, Sole M, Liew CC, Fein F, Sonnenblick EH: Hereditary and acquired cardiomyopathies in experimental animals; mechanical, biochemical and structural features. Ann N.Y. Acad Sci (317): 59–88, 1979.PubMedGoogle Scholar
  6. 6.
    Liew CC, Sole MJ: Studies of nuclear proteins in the heart tissue of the cardiomyopathic Syrian hamster; fractionation of phenol soluble non-histone proteins by two-dimensional Polyacrylamide gel electrophoresis. Circ Res (42): 628–636, 1978.PubMedGoogle Scholar
  7. 7.
    Ma TS, Baker JC, Bailey LE: Excitation-contraction coupling in normal and myopathic hamster hearts III: Functional deficiencies in interstitial glycoproteins. Cardiovasc Res (13): 568–577, 1979.PubMedCrossRefGoogle Scholar
  8. 8.
    Jasmin G, Solymoss B, Proscheck L: Therapeutic trials in hamster dystrophy. Ann N.Y. Acad Sci (317) 338–348, 1979.PubMedGoogle Scholar
  9. 9.
    Jasmin G, Bajusz E: Prevention of myocardial degeneration in hamsters with hereditary cardiomyopathy. In: Fleckenstein A, Rona G (eds) Recent advances in studies on cardiac structure and metabolism, Vol 6: Pathophysiology and morphology of myocardial cell alteration. University Park Press, Baltimore, 1975, pp 219–229.Google Scholar
  10. 10.
    Factor SM, Minase T, Cho S, Dominitz R and Sonnenblick EH: Microvascular spasm in the cardiomyopathic Syrian hamster: a preventable cause of focal myocardial necrosis. Circulation (66): 342–354, 1982.PubMedCrossRefGoogle Scholar
  11. 11.
    Geft IL, Fishbein MC, Ninomiya K, Hashida J, Chaux E, Yano J, Y-Rit J, Genov T, Shell W, Ganz W: Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis. Circulation (66): 1150–1153, 1982.PubMedCrossRefGoogle Scholar
  12. 12.
    Sole MJ, Lo C-M, Laird CW, Sonnenblick EH, Wurtman RJ: Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster. Circ Res (37): 855–862, 1975.PubMedGoogle Scholar
  13. 13.
    Sole MJ, Heike CJ, Jackobowicz DM: Increased dopamine in the failing hamster heart: transvesicular transport of dopamine limits the rate of norepinephrine synthesis. Am J Cardiol (49): 1682–1690, 1982.PubMedCrossRefGoogle Scholar
  14. 14.
    Lund DD, Schmid PG, Bhatnager RK, Roskoski R: Changes in parasympathetic and sympathetic neurochemical indices in hearts of myopathic hamsters. J Aut Nerv System (5) 237–246, 1982.CrossRefGoogle Scholar
  15. 15.
    Karliner JS, Alabaster C, Stephens H, Barnes P, Dollery C: Enhanced noradrenaline response in cardiomyopathic hamsters; possible relation to changes in adrenoreceptors studied by radioligand binding. Cardiovas Res (15): 296–304, 1981.CrossRefGoogle Scholar
  16. 16.
    Hunter EG, Elbrink J: Increased contractility in vascular smooth muscle of dystrophic hamsters. Can J Physiol Pharmacol (61) 182–185, 1983.PubMedCrossRefGoogle Scholar
  17. 17.
    Ostmann-Smith I: Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci (61): 265–272, 1981.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1985

Authors and Affiliations

  • M. J. Sole
  • S. M. Factor

There are no affiliations available

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