Skip to main content
SpringerLink
Log in

Stimulation of Vascular Prostacyclin Formation by Defibrotide: A New Strategy for Treatment of Acute Myocardial Ischaemia

  • Conference paper
Limitation of Infarct Size

Abstract

The effectiveness of pharmacological interventions to protect the ischaemic myocardium from irreversible injury, i.e. infarction, is a matter of controversy. While it is clear that the only effective therapeutic measure to prevent cell death is the restoration of coronary blood flow, for example by early thrombolysis, it is also evident that initially this might even aggravate the severity of cellular lesions by an inflammation-like process, originally described by Sommers and Jennings [28]. Therefore, pharmacological interventions for reducing ultimate infarct size or even preventing irreversible necrosis might be effective if they occur early after occlusion and/or improve the resistance of the injured myocardium against the two major detrimental factors: cellular calcium overload and oxygen toxicity [8, 25].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Araki H, Lefer AM (1980) Role of prostacyclin in the preservation of ischemic myocardial tissue in the perfused cat heart. Circ Res 47: 757–763

    PubMed  CAS  Google Scholar 

  2. Baller D, Bretschneider HJ, Hellige G (1981) A critical look at currently used indirect indices of myocardial oxygen consumption. Basic Res Cardiol 76: 163–181

    Article  PubMed  CAS  Google Scholar 

  3. Berti F, Rossoni G, Omini C, Folco G, Daffonchio L, Vigano T, Tondo C (1987) Defibrotide, an antithrombotic substance which prevents myocardial contracture in ischemic rabbit heart. Eur J Pharmacol 135: 375–382

    Article  PubMed  CAS  Google Scholar 

  4. Chien KR, Han A, Sen A, Buja LM, Willerson JT (1984) Accumulation of unesterified ara- chidonic acid in ischemic canine myocardium. Circ Res 54: 313–322

    PubMed  CAS  Google Scholar 

  5. DeChatelet LR, Long GD, Shirley PS, Bass DA, Thomas MJ, Henderson FW, Cohen MS (1982) Mechanism of the luminol-dependent chemiluminescence of human neutrophils. J Immunol 129: 1589–1593

    Google Scholar 

  6. Grodzinksa L, König E, Schrör K (1987) Defibrotide is equipotent to urokinase in stimulating arterial and venous thrombolysis. Pharmacol Res Commun (in press)

    Google Scholar 

  7. Gudewicz PW, Gilboa N (1987) Human urokinase-type plasminogen activator stimulates Chemotaxis of human neutrophils. Biochem Biophys Res Commun 147: 1176–1181

    Article  PubMed  CAS  Google Scholar 

  8. Hearse DJ, Humphrey SM, Bullock GR (1984) The oxygen paradox and the calcium paradox: two facets of the same problem? J Mol Cell Cardiol 10: 641–668

    Article  Google Scholar 

  9. Humphrey JM, Thomson RW, Gavin JB (1984) The influence of the no-reflow phenomenon on reperfusion and reoxygenation damage and enzyme release from anoxic and ischemic isolated rat hearts. J Mol Cell Cardiol 16: 915–930

    Article  PubMed  CAS  Google Scholar 

  10. Kato T, Wokalek H, Schöpf E, Eggert H, Ernst M, Rietschel ET, Fischer H (1981) Measurement of chemiluminescence in freshly drawn human blood. I. Role of granulocytes, platelets and plasma factors in zymosan-induced chemiluminescence. Klin Wochenschr 59: 203–211

    Article  PubMed  CAS  Google Scholar 

  11. Löbel P, Schrör K (1985) Selective stimulation of coronary vascular PGI2 but not of platelet thromboxane formation by defibrotide in the platelet perfused heart. Naunyn Schmiedebergs Arch Pharmacol 331: 125–130

    Article  PubMed  Google Scholar 

  12. Lucchesi BR, Mullane KM (1986) Leukocytes and ischemia-induced myocardial injury. Annu Rev Pharmacol Toxicol 26: 201–224

    Article  PubMed  CAS  Google Scholar 

  13. Mullane KM, McGiff JC (1985) Platelet depletion and infarct size in an occlusion-reperfu- sion model of myocardial ischemia in anaesthetized dogs. J Cardiovasc Pharmacol 7:733– 738

    Google Scholar 

  14. Niada R, Mantovani M, Prino G, Pescador R, Berti F, Omini C, Folco GC (1981) Antithrombotic activity of a polydeoxyribonucleotide substance extracted from mammalian organs: a possible link with prostacyclin. Thromb Res 23: 233–246

    Article  PubMed  CAS  Google Scholar 

  15. Niada R, Porta R, Pescador R, Mantovani M, Prino G (1985) Cardioprotective effects of defibrotide in acute myocardial ischemia in the cat. Thromb Res 38: 71–81

    Article  PubMed  CAS  Google Scholar 

  16. Niada R, Porta R, Tettamanti R, Pescador R, Mantovani M, Prino G (1987) Defibrotide in experimental myocardial ischemia in the cat. Effects on hemodynamics, energy metabolism and infarct size. Thromb Haemost 58: 353

    Google Scholar 

  17. Ogletree ML, Lefer AM, Smith JB, Nicolaou KC (1979) Studies on the protective effect of prostacyclin in acute myocardial ischemia. Eur J Pharmacol 56: 95–103

    Article  PubMed  CAS  Google Scholar 

  18. Pescador R, Mantovani M, Prino G, Madonna M (1983) Pharmacokinetics of defibrotide and of its profibrinolytic activity in the rabbit. Thromb Res 30: 1–11

    Article  PubMed  CAS  Google Scholar 

  19. Prinzen FW, Van der Vusse GJ, Arts T, Roemen THM, Coumans WA, Renemann RS (1984) Accumulation of nonesterified fatty acids in ischemic canine myocardium. Am J Physiol 247: 264–272

    Google Scholar 

  20. Rosalki SML (1967) Improved procedure for creatine phosphokinase determination. J Lab Clin Med 69: 696–705

    PubMed  CAS  Google Scholar 

  21. Schrör K (1987) Eicosanoids and myocardial ischaemia. Basic Res Cardiol 82: 235–243

    PubMed  Google Scholar 

  22. Schrör K, Hecker G (1987) Potent inhibition of superoxide anion generation by PGEX and the PGE analog OP-1206 in human PMN’s - unrelated to its antiplatelet, PGI2-like activity. Vasa (Suppl) 17: 11–16

    Google Scholar 

  23. Schrör K, Köhler P, Müller M, Peskar BA, Rösen P (1981) Prostacyclin-thromboxane interactions in the platelet perfused in vitro heart. Am J Physiol 241: 18–25

    Google Scholar 

  24. Schrör K, Ohlendorf R, Darius H (1981) Beneficial effects of a new carbacyclin derivative, ZK 36374, in acute myocardial ischemia. J Pharmacol Exp Ther 219: 243–249

    PubMed  Google Scholar 

  25. Shen AC, Jennings RB (1972) Myocardial calcium and magnesium in acute ischemic injury. Am J Pathol 67: 417–440

    PubMed  CAS  Google Scholar 

  26. Simpson PJ, Mitsos SE, Ventura A, Gallagher AP, Fantone JC, Abrams GD, Schork MA, Lucchesi BR (1987) Prostacyclin protects ischemic reperfused myocardium in the dog by inhibition of neutrophil activation. Am Heart J 113: 129–137

    Article  PubMed  CAS  Google Scholar 

  27. Smith EF III, Kloster G, Stöcklin G, Schrör K (1984) Effect of iloprost (ZK 36374) on membrane integrity in ischemic rabbit hearts. Biomed Biochim Acta 43: 155–158

    CAS  Google Scholar 

  28. Sommers HM, Jennings RB (1964) Experimental acute myocardial infarction induced by temporary or permanent occlusion of a coronary artery. Lab Invest 13: 1491–1503

    PubMed  CAS  Google Scholar 

  29. Thiemermann C, Löbel P, Schrör K (1985) Usefulness of defibrotide in protecting ischemic myocardium from reperfusion damage. Am J Cardiol 56: 978–982

    Article  PubMed  CAS  Google Scholar 

  30. Thiemermann C, Schrör K (1984) Comparison of the thromboxane synthetase inhibitor daz- oxiben and the prostacyclin mimemtic iloprost (ZK 36 374) in an animal model of acute myocardial ischemia and reperfusion. Biomed Biochim Acta 43: 151–154

    CAS  Google Scholar 

Download references

Authors
  1. K. Schrör
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ch. Thiemermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Löbel
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dept. of Cardiology, University Hospital Rudolf Virchow, Spandauer Damm 130, D-1000, Berlin 19, Germany

    Horst Schmutzler , Wolfgang Rutsch  & Frank Christopher Dougherty ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Schrör, K., Thiemermann, C., Löbel, P. (1989). Stimulation of Vascular Prostacyclin Formation by Defibrotide: A New Strategy for Treatment of Acute Myocardial Ischaemia. In: Schmutzler, H., Rutsch, W., Dougherty, F.C. (eds) Limitation of Infarct Size. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73585-1_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73585-1_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-19148-3

  • Online ISBN: 978-3-642-73585-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation