Heart and Vessels

, Volume 13, Issue 2, pp 58–62 | Cite as

Acute hemodynamic and coronary circulatory effects of experimental autoimmune myocarditis

  • Bruce J. Friedman
  • Oleg Y. Grinberg
  • Nora R. Ratcliffe
  • Harold M. Swartz
  • William F. Hickey


Myocarditis and progression to cardiomyopathy is associated with focal spasm and reperfusion of the coronary microcirculation. Experimental autoimmune myocarditis (EAM), induced with cardiomyosin peptide-specific T cells in Lewis rats, was hypothesized to cause acute hemodynamic and coronary vasculature changes. Fifteen experimental animals (5 each at 1, 2, and 3 weeks after T-cell injection) and eight controls were studied using the constant pressure variant of the isolated heart. Coronary resistance decreased while coronary flow increased (P < 0.05) in EAM hearts after the first week. Rate-pressure product, +dP/dt and −dP/dt, decreased while the heart/body weight ratio increased (P < 0.05) compared with controls at 1 week but not at 2 or 3 weeks. Mean local myocardialPO2, which reflects local oxygen delivery and consumption, and MVO2 were not different for EAM hearts. However, compared with controls EAM myocardialPO2 varied more widely and was often beyond the usual range, suggesting the occurrence of localized hypoxic and hyperoxic areas. In summary, after the first week there was a significant decrease in coronary resistance in the EAM animals, which required higher flow to maintain a similar perfusion pressure. These changes in coronary resistance and flow along with the heterogeneity and extremes of local myocardialPO2 levels without a significant change in MVO2 may be explained by postulating development of low-resistance, high-flow hyperoxic areas which steal flow, thus causing hypoxia in other areas.

key words

Coronary circulation Experimental allergic myocarditis 


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  1. 1.
    Wegmann KW, Zhao W, Griffin AC, Hickey WF (1994) Identification of myocarditogenic peptides derived from cardiac myosin capable of inducing experimental allergic myocarditis in the Lewis Rat. J Immunol 153:892–900Google Scholar
  2. 2.
    Kodama M, Matsumoto Y, Fujiwara M, Masani F, Izumi T, Shibata A (1990) A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 57:250–262Google Scholar
  3. 3.
    Dong R, Liu P, Wee L, Butany J, Sole MJ (1992) Verapamil ameliorates the clinical and pathological course of murine myocarditis. J Clin Invest 90:2022–2030Google Scholar
  4. 4.
    Factor SM, Minase T, Cho S, Dominitz R, Sonnenblick EH (1982) Microvascular spasm in the cardiomyopathic Syrian hamster: a preventable cause of focal myocardial necrosis. Circulation 66:342–354Google Scholar
  5. 5.
    Figulla HR, Vetterlein F, Glaubitz M, Kreuzer H (1987) Inhomogeneous capillary flow and its prevention by verapamil and hydralazine in the cardiomyopathic Syrian hamster. Circulation 76:208–216Google Scholar
  6. 6.
    Friedman BJ, Grinberg OY, Isaacs K, Walczak TM, Swartz HM (1995) Myocardial oxygen tension and relative capillary density in isolated perfused rat hearts. J Mol Cell Cardiol 27:2551–2558Google Scholar
  7. 7.
    Swartz HM, Dunn J, Grinberg O, O'Hara J, Walczak T (1998) What does EPR oximetry with solid particles measure and how does this related to other measures of pO2. Oxygen Trans Tissue XIX 428:663–670Google Scholar
  8. 8.
    Barlow CH, Chance B (1976) Ischemic areas in perfused rat hearts: measurement by NADH fluorescence photography. Science 193:909–910Google Scholar
  9. 9.
    Ince C, Ashruf JF, Avontuur AM, Wieringa PA, Spaan JAE, Bruining HA (1993) Heterogeneity of the hypoxic state in rat heart is determined at capillary level. Am J Physiol 264:H294-H301Google Scholar
  10. 10.
    Steenbergen C, Deleeuw G, Barlow C, Chance B, Williamson JR (1977) Heterogeneity of the hypoxic state in perfused rat heart. Circ Res 41:606–615Google Scholar
  11. 11.
    Esaki T, Hayashi T, Asai Y, Kumar TN, Kano H, Muto E, Iguchi A (1997) Expression of inducible nitric oxide synthase in T lymphocytes and macrophages in vessels with advanced atherosclerosis. Heart Vessels Suppl 12:89–92Google Scholar
  12. 12.
    Hirono S, Islam O, Nakazawa M, Yoshida Y, Kodama M, Shibata A, Izumi T, Imai S (1997) Expression of inducible nitric oxide synthase in rat experimental autoimmune myocarditis with special reference to changes in cardiac hemodynamics. Circ Res 80:11–20Google Scholar
  13. 13.
    Moncada S, Higgs A (1993) The L-arginine-nitric-oxide pathway. N Engl J Med 329:2002–2012Google Scholar
  14. 14.
    Herzum M, Weller R, Jomaa H, Wiertrzychowski F, Pankuweit S, Mahr P, Maisch B (1995) Left ventricular hemodynamic parameters in the course of acute experimental coxsackievirus B 3 myocarditis. J Mol Cell Cardiol 27:1573–1580Google Scholar
  15. 15.
    Kotaka M, Kitaura Y, Deguchi H, Kawamura K (1990) Experimental influenza A virus myocarditis in mice. Light and electron microscopic, virologic and hemodynamic study. Am J Pathol 136:409–419Google Scholar
  16. 16.
    Rubboli A, Sobotka PA, Euler DE (1994) Effect of acute edema on left ventricular function and coronary resistance in the isolated rat heart. Am J Physiol. 36:H1054-H1061Google Scholar
  17. 17.
    Masuda M, Chang-Chun C, Cho BC, Flameng W (1994) Coronary reserve and contractile reserve in crystalloidand blood-perfused rabbit hearts. Heart Vessels 9:175–182Google Scholar
  18. 18.
    Friedman BJ, Grinberg OY, Grinberg SA, Swartz HM (1997) Myocardial oxygen tension in isolated erythrocyte-perfused rat hearts and comparison with crystalloid media. J Mol Cell Caridol 29:2855–2858Google Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • Bruce J. Friedman
    • 1
  • Oleg Y. Grinberg
    • 2
  • Nora R. Ratcliffe
    • 3
  • Harold M. Swartz
    • 2
  • William F. Hickey
    • 3
  1. 1.Division of CardiologyLebanonUSA
  2. 2.Department of RadiologyDartmouth-Hitchcock Medical CenterLebanonUSA
  3. 3.Department of PathologyDartmouth-Hitchcock Medical CenterLebanonUSA

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