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Catecholamine-induced cardiac necroses: Protective effect of leucocytopenia, influence of an S2 antagonist, thromboxanesynthetase inhibitor and prostacycline analogue

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Summary

The influence of various drugs and leucocytopenia (induced by cyclosphamid) on isoproterenol (40 mg/kg, s.c.)-induced cardiac necroses was investigated in female SPF Sprague Dawley rats. The influence of fibrinogen reduction was investigated in spontaneously hypertensive rats (SHR). 8–15% of the area of 15 cross-sections were evaluated with a computer-aided morphometric device allowing classification of number and area of necroses. The reduction of number and area of necroses amounted to approximately: 50% by prostacyclin analogue, 25% by S2 inhibition (ketanserin). Inhibition of thromboxane synthesis and fibrinogen reduction from elevated values (200 mg/dl) below the limit of detection by infusion of 35 U/kg Ancrod in SHR had no significant effects, where in SHR only 10 mg/kg isoproterenol were tolerated with a higher extent of necrosis formation.

Leucocytopenia caused a reduction of necroses of over 90%. The condition of mismatch of oxygen consumption and supply induced by high doses of isoproterenol can be considered a model of angina pectoris. The effect of leucocytopenia indicates an essential role of leucocytes in necrosis formation in both situations.

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References

  1. Bednar M, Smith B, Pinto A, Mullane KM (1985) Neutrophil depletion suppresses 111-In labeled platelet accumulation in infarcted myocardium. J Cardiovasc Pharmacol 7:906–912

    Google Scholar 

  2. Bevilacqua MP, Wheeler ME, Pober JS, Fiers W, Mendrick DL, Cotran RS, Gimbrone MA (1987) Endothelial-dependent mechanisms of leukocyte adhesion-regulation by interleukin-1 and tumor necrosis factor. In: Movat HZ (ed) Leukocyte Emigration and Sequalae. S. Karger AG, Basel, pp 79–93

    Google Scholar 

  3. Blasig IE, Muschick P, Modersohn D, Will-Shahab L, Loewe H (1981) Lactate accumulation and blood flow reduction in rat myocardium after isoproterenol overdosage. In: Szekeres L, Papp JP, Takats I (eds) Pathomechanism and Prevention of Sudden Cardiac Death due to Coronary Insufficiency. International Symposium of the Socialist Countries, Szeged, Hungary, pp 69–77

  4. Blasig IE, Muschenick P, Rohde E, Richter R, Modersohn D, Löwe H (1984) Can blood flow reduction after isoproterenol overdosage induce myocardial ischemia? In: Abhandlungen der Akademie der Wissenschaften der DDR, Abteilung Mathematik-Naturwissenschaften-Technik Jahrgang 1984, Nr. 1N: Cellular and Molecular Aspects of the Regulation of the Heart. Akademie-Verlag, Berlin, pp 243–246

    Google Scholar 

  5. Braquet P, Touqui L, Shen TY, Vargaftig B (1987) Perspectives in platelet-activating factor research. Pharmacological reviews 39:98–135

    Google Scholar 

  6. Bussolini F, Camussi G, Breviario F, Bertocchi F, Ghigo D, Pescarmona GP, Aglietta M, Garbarino G, Bosia A, Dejana E (1988) Endothelial cells and inflammation: the role of plateletactivating factor, interleukin 1, tumor necrosis factor, and circulating neutrophils. In: Braquet P (ed) Platelet-activating factor and cell immunology. Karger, Basel, New trends in lipid mediators research (1), pp 135–143

    Google Scholar 

  7. Engler R (1987) Granulocytes and oxidative injury in myocardial ischemia and reperfusion. Federation Proceedings 46:2395–2396

    Google Scholar 

  8. Haft JJ, Kranz PD, Albert F, Oestreicher R (1973) Protection against epinephrine induced myocardial necroses with clofibrate. Am Heart J 86:805–810

    Google Scholar 

  9. Kammermeier H, Ober M (1985) Essential contribution of thrombocytes to the occuence of catecholamine-induced cardiac necroses. J Mol Cell Cardiol 17:371–376

    Google Scholar 

  10. Kraemer R, Mullane KM (1989) Neutrophils delay functional recovery of the post-hypoxic heart of the rabbit. J Pharmacol Exp Ther 251:620–626

    Google Scholar 

  11. Krawisz JE, Sharon P, Stenson WF (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 87:1344–1350

    Google Scholar 

  12. Lucchesi BR (1983) Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circ 67:1016–1023

    Google Scholar 

  13. Neumann FJ, Waas W, Diehm C, Weiss T, Haupt H-M, Zimmermann R, Tillmanns H, Kuebler W (1990) Activation and decreased deformability of neutrophils after intermittent claudication. Circ 82:922–929

    Google Scholar 

  14. Peres-Polon VL, Correa FMA (1985) Central mechanisms of the isoprenaline-induced hypotension in anesthetized and conscious rats. Gen Pharmacol 15:505–509

    Google Scholar 

  15. Remie R, Knot HJ, Kolker HJ, Zaagsma J (1988) Pronounced facilitation of endogenous noradrenaline release by presynaptic beta-2-adrenoceptors in the vasculature of freely moving rats. N-S Arch Pharmacol 338:215–220

    Google Scholar 

  16. Rona G, Chappel CI, Balazs T, Gaudry R (1957) An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. Arch Path 67:443–455

    Google Scholar 

  17. Schmid-Schönbein H (1977) Microrheology of erythrocytes and thrombocytes, blood viscosity and distribution of blood flow in the microcirculation. In: Altmann WH (et al) (ed) Handbuch der allgemeinen Pathologie. Springer-Verlag, Berlin Heidelberg New York, pp 289–384

    Google Scholar 

  18. Simpson PJ, Fantone JC, Mickelson JK, Gallagher KP, Lucchesi BR (1988) Identification of a time window for therapy to reduce experimental canine myocardial injury: Suppression of neutrophil activation during 72 hours of reperfusion. Circ Res 63:1070–1079

    Google Scholar 

  19. Smith JK, Grisham MB, Granger DN, Korthuis RJ (1989) Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle. Am J Physiol 256:H789–H793

    Google Scholar 

  20. Stewart D, Holtz J, Pohl U, Bassenge E (1987) Balance between endothelium-mediated dilating and direct constricting actions of serotonin on resistance vessels in the isolated rabbit heart. European Journal of Pharmacology 143:131–134

    Google Scholar 

  21. Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T (1983) Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 132:345–352

    Google Scholar 

  22. Wardlaw AJ, Moqbel R, Kurihara K, Walsh G, Kay AB (1988) Role of PAF in leucocyte activation and chemotaxis. In: Braquet P (ed) The role of platelet-activating factor in immune disorders. Karger, Basel, New Trends in Lipid Mediators Research (2), pp 1–9

    Google Scholar 

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Author notes

  1. H. Kammermeier

    Present address: Institut für Physiologie, Medizinische Fakultät der RWTH Aachen, Pauwelsstr. 30, W-5100, Aachen, FRG

Authors and Affiliations

  1. Institut für Physiologie, Medizinische Fakultät der RWTH Aachen, Pauwelsstr. 30, W-5100, Aachen, FRG

    L. Classen & G. Michalsky

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  1. L. Classen
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  2. G. Michalsky
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  3. H. Kammermeier
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Additional information

Preliminary results of parts of this study were published in Z. Kardiol. 1987; 83; S1: P 297 and J. Mol. Cell. Cardiol. 1989; 21 S IV: FC 16.

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Classen, L., Michalsky, G. & Kammermeier, H. Catecholamine-induced cardiac necroses: Protective effect of leucocytopenia, influence of an S2 antagonist, thromboxanesynthetase inhibitor and prostacycline analogue. Basic Res Cardiol 88, 52–59 (1993). https://doi.org/10.1007/BF00788530

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  • DOI: https://doi.org/10.1007/BF00788530

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