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Inotropic and electrophysiological action of humoral factors released in cardiogenic shock after acute myocardial infarction

Inotrope und elektrophysiologische Wirkungen von humoralen Faktoren beim kardiogenen Schock nach akutem Myokardinfarkt

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Summary

The inotropic and electrophysiological effects of plasma obtained from patients and experimental dogs during cardiogenic shock following acute myocardial infarction were studied. Changes in the isometric contraction and the intracellular action potential were determined in isolated papillary muscles of rabbits. Control plasma collected from normal subjects produced no significant changes in the contraction or the electrical parameters. Plasma from shock patients decreased peak force by 42% and the maximum rate of force development by 38% in comparison to control values; the time to peak of contraction, the relaxation time and the action potential parameters were not significantly altered. Corresponding results were obtained with plasma from dogs before and during experimental cardiogenic shock. Biochemical determinations failed to identify a single specific “myocardial depressant factor” in the plasma of patients and dogs with cardiogenic shock. The results suggest that (1) various humoral factors released during cardiogenic shock may depress the contractile function of cardiac muscle and (2) that the observed negative inotropic effect is not due to electrical changes in the cell membrane.

Zusammenfassung

Die Irreversibilität eines kardiogenen Schocks nach Myokardinfarkt soll angeblich wesentlich durch die Freisetzung eines humoralen, negativ inotropen Peptids, des “myocardial depressant factor” (MDF), mibestimmt werden. Bei Patienten und Hunden wurde Plasma während eines kardiogenen Schocks nach akutem Myokardinfarkt gewonnen. Gemessen wurde die Wirkung von Plasmadialysaten auf die isometrische Kontraktion und auf intrazelluläre Aktionspotentiale an isolierten Papillarmuskeln von Kaninchen in vitro. Kontrollplasma von herzgesunden Normalpersonen hatte keinen signifikanten Einfluß auf die Kontraktion und die elektrischen Parameter. Wechsel der Superfusions-flüssigkeit von Kontrollplasma auf Schockplasma verursachte eine signifikante Abnahme von Kontraktionsamplitude und maximaler Kontraktionsgeschwindigkeit um 30–40%; Kontraktionszeit, Relaxationszeit und die elektrophysiologischen Parameter des Aktionspotentials blieben unverändert. Ähnliche Ergebnisse wurden mit Plasmaproben von Hunden beobachtet, die während eines experimentellen kardiogenen Schocks entnommen wurden. Biochemische Untersuchungen mit der Polyacrylamid-Gel-Elektrophorese und der High-Voltage-Elektrophorese ergaben keinen Unterschied zwischen den Peptidfraktionen in Kontrollplasma und Schockplasma. Die Ergebnisse deuten auf eine Beteiligung von unspezifisch negativ inotropen Plasmafaktoren bei der Entstehung eines kardiogenen Schocks hin; dagegen konnte das von mehreren Autoren postulierte spezifische MDF-Peptid mit den angewendeten empfindlichen analytischen Verfahren nicht nachgewiesen werden.

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References

  1. Thomas, M., R. Malmcrona, J. P. Shillingford: Haemodynamic changes in patients with acute myocardial infarction. Circulation31, 811–823 (1965).

    PubMed  Google Scholar 

  2. Bleifeld, W., D. Mathey, R. Hanrath, H. Buss, S. Effert: Infarct size estimated from serial serum creatine phosphokinase in relation to left ventricular hemodynamics. Circulation55, 303–311 (1977).

    PubMed  Google Scholar 

  3. Lefer, A. M.: Blood borne humoral factors in the pathophysiology of circulatory shock. Circulat. Res.32, 129–139 (1973).

    Google Scholar 

  4. Selkurt, E. E.: Status of investigative aspects of hemorrhagic shock. Fred. Proc.29, 1832–1835 (1970).

    Google Scholar 

  5. Lefer, A. M.: Role of a myocardial depressant factor in the pathogenesis of circulatory shock. Fed. Proc.29, 1836–1947 (1970).

    PubMed  Google Scholar 

  6. Brand, E. D., A. M. Lefer: Myocardial depressant factor in plasma from cats in irreversible post-oligemic shock. Proc. Soc. exp. Biol. (N.Y.)122, 200–203 (1966).

    Google Scholar 

  7. Lovett, W. L., S. J. Wangensteen, T. M. Glenn, A. M. Lefer: Presence of a myocardial depressant factor in patients in circulatory shock. Surgery70, 223–230 (1971).

    PubMed  Google Scholar 

  8. Lefer, A. M., J. Martin: Relationship of plasma peptides to the myocardial depressant factor in hemorrhagic shock in cats. Circulat. Res.26, 59–69 (1970).

    PubMed  Google Scholar 

  9. Bretag, A.: Synthetic interstitial fluid for isolated mammalian tissue. Life Sci.8, 319–329 (1969).

    Article  Google Scholar 

  10. Senges, J., H. Katus, W. Kübler: Action of anaphylaxis and histamine on isolated mammalian ventricles: contractile hyperactivation and changes of membrane potentials. J. Pharmacol. Exper. Therap.198, 668–679 (1976).

    Google Scholar 

  11. Davis, B.: Disc electrophoresis II: Method and application to human proteins. Ann. N.Y. Acad. Sci.121, 404–427 (1964).

    PubMed  Google Scholar 

  12. Wieland, Th., G. Pfleiderer: Neuere Anwendungen der Hochspannungselektrophorese. Angew. Chemie69, 199–201 (1957).

    Google Scholar 

  13. Lefer, A. M.: Myocardial depressant factor and circulatory shock. Klin. Wschr.52, 358–370 (1974).

    Article  PubMed  Google Scholar 

  14. Okuda, T., T. Fukui: Myocardial depressant factor — a peptide: its significance in cardiogenic shock. Jap. Circulat. J.38, 497–508 (1974).

    Google Scholar 

  15. Crampton, R. S., S. L. Wangensteen, W. L. Lovett, J. N. Morris Jr., H. Harris, R. Weitzmann, T. M. Glenn, A. M. Lefer: Production of a myocardial depressant factor in shock following acute myocardial infarction: Preliminary evaluation of treatment with methylprednisolone. Amer. J. Cardiol.29, 247–258 (1972).

    Article  PubMed  Google Scholar 

  16. Glenn, T. M., A. M. Lefer, J. B. Martin, W. L. Lovett, J. N. Morris, S. L. Wangensteen: Production of a myocardial depressant factor in cardiogenic shock. Amer. Heart J.82, 78–85 (1971).

    Article  PubMed  Google Scholar 

  17. Lefer, A. M., J. Martin: Mechanism of the protective effect of corticosteroids in hemorrhagic shock. Amer. J. Physiol.216, 314–320 (1969).

    PubMed  Google Scholar 

  18. Haglund, U., O. Lundgreen: Cardiovascular effects of blood borne material released from the cat small intestine during simulated shock conditions. Acta physiol. scand.89, 558–570 (1973).

    PubMed  Google Scholar 

  19. Lillehei, R. C.: The intestinal factor in irreversible hemorrhagic shock. Surgery42, 1043–1054 (1957).

    PubMed  Google Scholar 

  20. Kuida, H.: Discussion of “the intestinal circulation in shock”. Gastroenterology52, 458–460 (1967).

    PubMed  Google Scholar 

  21. Carter, D., A. Einheber: Intestinal ischemic shock in germ-free animals. Surg. Gynecol. Obstet.122, 66–76 (1966).

    PubMed  Google Scholar 

  22. Lefer, A. M., M. J. Rovetto: Influence of a myocardial depressant factor on physiologic properties of cardiac muscle. Proc. Soc. exp. Biol. (N.Y.)134, 269–273 (1970).

    Google Scholar 

  23. Williams, L. F. Jr., A. H. Goldberg, B. J. Polansky, J. J. Byrne: Myocardial effects of intestinal ischemia. J. Surg. Res.9, 319–323 (1969).

    Article  PubMed  Google Scholar 

  24. Sonnenblick, E. H.: Active state in heart muscle: its delayed onset and modification by inotropic agents. J. Gen. Physiol.50, 661–676 (1967).

    Article  PubMed  Google Scholar 

  25. Braunwald, E., J. Ross, E. H. Sonnenblick: Mechanisms of contraction of the normal and failing heart. New Engl. J. Med., Medical Progress Series Boston (1967).

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With 3 figures and 7 tables

This work was supported by the German Research Foundation within the SFB 90 “Cardiovasculäres System”. Dr.Mizutani is a Research Fellow of the Alexander-von-Humboldt-Stiftung.

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Senges, J., Mizutani, T., Pelzer, D. et al. Inotropic and electrophysiological action of humoral factors released in cardiogenic shock after acute myocardial infarction. Basic Res Cardiol 73, 147–159 (1978). https://doi.org/10.1007/BF01906750

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