Skip to main content
SpringerLink
Log in
Book cover

Prostacyclin and Its Stable Analogue Iloprost pp 179–194Cite as

Myocardial Ischemia: The Potential Therapeutic Role of Prostacyclin and Its Analogues

  • Conference paper

Abstract

Prostacyclin (PGI2) and its stable analogues are potentially valuable therapeutic agents in at least three important cardiovascular disorders. By virtue of the vasodilatory properties of these agents and their ability to inhibit platelet activation by virtually all aggregating stimuli PGI2 analogues may be effective anti–thrombotic agents in vivo. Romson et al. [41] demonstrated that PGI2 infusion in the anesthetized dog was effective in preventing coronary artery thrombosis. Furthermore, administration of low dose PGI2 concomittantly with a phosphor–diesterase inhibitor, potentiated the antithrombotic effects of PGI2 without the decrease in blood pressure associated with higher doses of the prostanoid [43, 44].

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

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. Bannister JV, Bannister WH, Hill HAO, Thornally PI (1982) Enhanced production of hydroxyl radicals by the xanthine-xanthine oxidase reaction in the presence of lactoferrin. Biochim Biophys Acta 715–116–120

    Article  PubMed  CAS  Google Scholar 

  3. Bednar M, Smith B, Pinto A, Mullane KM (1985) Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function. Circ Res 57: 131–141

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. Biochem J 134: 707–716

    PubMed  CAS  Google Scholar 

  6. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527–605

    PubMed  CAS  Google Scholar 

  7. Egan KR, Gale PH, Kuehl FA (1974) Reduction of hydroperoxides in the prostaglandin biosynthetic pathway by a microsomal peroxidase. J Biol Chem 254: 3295–3302

    Google Scholar 

  8. Fantone JC, Kunkel SL, Ward PA, Zurier RB (1980) Suppression by prostaglandin Ei of vascular permeability induced by vasoactive mediators. J Immunol 125: 2591–2595

    PubMed  CAS  Google Scholar 

  9. Fantone JC, Kunkel SL, Ward PA, Zurier RB (1981) Suppression of human polymorpho-nuclear leukocyte function after intravenous infusion of PGE1 Prostaglandins Leukotrienes Med 2: 195

    Google Scholar 

  10. Fantone JC, Marasco WA, Elgas LJ, Ward PA (1983) Anti-inflammatory effects of prostaglandin Ej: In vivo modulation of the formyl peptide chemotactic receptor on the rat neutrophil. J Immunol 130: 1495–1497

    Google Scholar 

  11. Fantone JC, Kinnes DA (1983) Prostaglandin E1 and prostaglandin I2 modulation of superoxide production by human neutrophils. Biochem Biophys Res Commun 113: 506–512

    Article  PubMed  CAS  Google Scholar 

  12. Fantone JC, Kunkel SL, Zurier RB (1984) Effects of prostaglandins on in vivo immune and inflammatory reactions. In: Goodwin J (ed) Prostaglandins and immunity. Martinez and Nijhoff, Boston, pp 123–146

    Google Scholar 

  13. Fantone JC, Marasco WA, Elgas LJ, Ward PA (1984) Stimulus specificity of prostaglandin inhibition of rabbit polymorphonuclear leukocyte lysosomal enzyme release and superoxide anion production. Am J Pathol 115: 9–16

    PubMed  CAS  Google Scholar 

  14. Fantone JC, Ward PA (1982) Role of oxygen derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107: 397–418

    CAS  Google Scholar 

  15. Gobel FL, Nordsstrom LA, Nelson RR, Jorgenson CR, Wang Y (1978) The rate pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 57: 549–556

    PubMed  CAS  Google Scholar 

  16. Ham EA, Soderman DD, Zanetti ME, Dougherty HW, McCauley E, Kuehl F (1983) Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci USA 80: 4349–4353

    Article  PubMed  CAS  Google Scholar 

  17. Hearse DJ, Humphrey SM, Nayler WG, Slade A, Border D (1975) Ultrastructural damage associated with reoxygenation of the anoxic myocardium. J Mol Cell Cardiol 7: 315–324

    Article  PubMed  CAS  Google Scholar 

  18. Heyndricks GR, Baig H, Neilens D, Leusen I, Fishbein MC, Vatner SF (1978) Depression of regional blood flow and wall thickening after brief coronary occlusion. Am J Physiol 234: H653–H659

    Google Scholar 

  19. Jennings RB, Ganote GB, Kloner RA, Whalen DA, Hamilton DG (1975) Explosive cell swelling of myocardial cells irreversibly injured by transmural ischemia. In: Fleckenstein A, Rona G (eds) Pathophysiology and morphology of myocardial cell alteration. University Park Press, Baltimore (Recent advances in studies on cardiac structure and metabolism, vol 6 )

    Google Scholar 

  20. Jennings RB, Reimer K (1979) Biology of experimental acute myocardial ischemia and in–farction. In: Hearse DJ, deLeiris J (eds) Enzymes in cardiology: diagnosis and research. Wiley, Chichester, pp 21–57

    Google Scholar 

  21. Johnson KJ, Varani J, Oliver J, Ward PA (1979) Immunologic vasculitis in beige mice with deficiency of leukocytic neutral proteases. J Immunol 122: 1807–1812

    PubMed  CAS  Google Scholar 

  22. Johnson KJ, Ward PA (1981) Role of oxygen metabolites in immune complex injury of lung. J Immunol 122: 1807–1812

    Google Scholar 

  23. Jolly SR, Kane WJ, Bailie MB, Abrams GD, Lucchesi BR (1984) Canine myocardial reperfusion injury: its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 54: 277–285

    PubMed  CAS  Google Scholar 

  24. Jolly SR, Schumacher WA, Kunkel SL, Abrams GD, Liddicoat J, Lucchesi BR (1985) Platelet depletion in experimental myocardial infarction. Basic Res Cardiol 80: 269–279

    Article  PubMed  CAS  Google Scholar 

  25. Jugdutt BI, Hutchins GM, Bulkley BH, Becker LC (1981) Dissimilar effects of prostacyclin, prostaglandin Ex and prostaglandin E2, on myocardial infarct size after coronary occlusion in conscious dogs. Circ Res 49: 685–700

    PubMed  CAS  Google Scholar 

  26. Kloner R, Braunwald E (1980) Observations on experimental myocardial ischemia. Cardiovasc Res 14: 371–395

    Article  PubMed  CAS  Google Scholar 

  27. Lefer AM, Ogletree MNL, Smith JB, Silver MJ, Nicolaou KC, Barnette WE, Gasic GP (1978) Prostacyclin: a potentially valuable agent for preserving ischemic myocardial tissue in acute myocardial ischemia. Science 200: 52–54

    Article  PubMed  CAS  Google Scholar 

  28. Lucchesi BR, Romson JL, Jolly SR (1984) Do leukocytes influence infarct size? In: Hearse DJ, Yellon DM (eds) Therapeutic approaches to myocardial infarct size limitation. Raven, New York, pp 219–248

    Google Scholar 

  29. Maroko PR, Kjekshus JK, Sobel BE, Watanabe T, Covell JW, Ross J, Braunwald E (1971) Factors influencing infarct size following experimental coronary artery occlusions. Circulation 53: 67–82

    Google Scholar 

  30. Marone G, Thomas LC, Lichtenstein LM (1980) The role of agonists that activate adenylate cyclase in the control of cAMP metabolism and enzyme release by human polymorphonuclear leukocytes. J Immunol 125: 2277–2283

    PubMed  CAS  Google Scholar 

  31. McCord JM, Fridovitch I (1969) Superoxide dismutase: an enzymic function for erythrocu-prein (hemocuprein). J Biol Chem 244: 6049–6055

    PubMed  CAS  Google Scholar 

  32. Meerson FZ, Gagan VE, Kozlow YuP, Belkin LM, Arkipenko YV (1982) The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart. Basic Res Cardiol 77:465–480

    Article  PubMed  CAS  Google Scholar 

  33. Melin JA, Becker LC (1983) Salvage of ischemic myocardium by prostacyclin during experimental myocardial infarction. J Am Coll Cardiol 2: 279–286

    Article  PubMed  CAS  Google Scholar 

  34. Nicholson NS, Smith SL, Taite BB, Krueger A, Fuller GC (1985) Evaluation of a stable 5-F prostacyclin analogue as an antithrombotic agent in hemodialysis. Submitted to Drugs Under Experimental Research

    Google Scholar 

  35. Ogletree ML, Lefer AM (1978) Prostaglandin-induced preservation of the ischemic myocardium. Circ Res 42: 218–224

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Opie LH (1979) Energy metabolism of heart muscle during hypoxia and ischemia. In: Gross F (ed) Modulation of sympathetic tone in the treatment of cardiovascular diseases. Huber, Bern, p 43

    Google Scholar 

  38. Otani H, Tanaka H, Inoue T, Umemoto M, Omoto K, Tanaka K, Sato T, Osako T, Masuda A, Nonoyama A, Kagawa T (1984) In vitro study on contribution of oxidative metabolism of isolated rabbit heart mitochondria to myocardial reperfusion injury. Circ Res 55:168– 175

    Google Scholar 

  39. Rao PS, Mueller HS (1983) Lipid peroxidation and acute myocardial ischemia. Adv Exp Med Biol 161: 347–363

    PubMed  CAS  Google Scholar 

  40. Rivkin I, Rosenblatt J, Becker EI (1975) The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils. J Immunol 115: 1126–1134

    PubMed  CAS  Google Scholar 

  41. Romson JL, Haack DW, Abrams GD, Lucchesi BR (1981) Prevention of occlusive coronary artery thrombosis by prostacyclin infusion in the dog. Circulation 64: 906–914

    Article  PubMed  CAS  Google Scholar 

  42. Romson JL, Hook BG, Rigot VH, Schork MA, Swanson DP, Lucchesi BR (1982) The effects of ibuprofen on accumulation of Ill–indium labeled platelets and leukocytes in experimental myocardial infarction. Circulation 66: 1002–1011

    Article  PubMed  CAS  Google Scholar 

  43. Romson JL, Hook BG, Lucchesi BR (1983) Potentiation of the antithrombotic effect of prostacyclin by simultaneous administration of aminophylline in a canine model of coronary artery thrombosis. J Pharmacol Exp Ther 227: 288–294

    PubMed  CAS  Google Scholar 

  44. Romson JL, Hook BG, Kunkel SL, Abrams GD, Schork MA, Lucchesi BR (1983) Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation 67: 1016–1023

    Article  PubMed  CAS  Google Scholar 

  45. Roos D, Weening RS, Wyss SR (1980) Protection of human neutrophils by endogenous catalase: studies with cells from catalase deficient individuals. J Clin Invest 65: 1515–1522

    Article  PubMed  CAS  Google Scholar 

  46. Schror K, Addicks K, Darius H, Ohlendorf R, Rosen P (1981) PGI2 inhibits ischemia induced platelet activation and prevents myocardial damage by inhibition of catecholamine release from adrenergic nerve terminals. Evidence for cAMP as common denominator. Thromb Res 21: 175–180

    Article  PubMed  CAS  Google Scholar 

  47. Schror 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  CAS  Google Scholar 

  48. Schror K, Darius H, Ohlendorf R, Matzky R, Klaus W (1982) Dissociation of antiplatelet effects from myocardial cytoprotective activity during acute myocardial ischemia in cats by a new carbacyclin derivative (ZK 36375). J Cardiovasc Pharmacol 4: 554–561

    PubMed  CAS  Google Scholar 

  49. Schumacher WA, Lee EC, Lucchesi BR (1985) Augmentation of streptokinase thrombolysis by heparin and prostacyclin. J Cardiovasc Pharmacol 7: 739–746

    Article  PubMed  CAS  Google Scholar 

  50. Simpson PS, Mitsos SE, Ventura A, Gallagher KP, Fantone JC, Abrams GD, Schork MA, Lucchesi BR (1986) Prostacyclin protects ischemic-reperfused myocardium in the dog by inhibition of neutrophil activation. Am Heart J (in press)

    Google Scholar 

  51. Smith RJ, Iden SS (1980) Pharmacological modulation of chemotactic factor-elicited release of granule-associated enzymes from human neutrophils. Biochem Pharmacol 29:2389– 2395

    Article  PubMed  CAS  Google Scholar 

  52. Smith EF, Lefer AM (1981) Stabilization of cardiac lysosomal and cellular membranes in protection of ischemic myocardium due to coronary occlusion: efficacy of the nonsteroidal anti-inflammatory agent, naproxen. Am Heart J 101: 394–402

    Article  PubMed  CAS  Google Scholar 

  53. Thiemermann C, Steinhagen-Thiessen E, Schror K (1984) Inhibition of oxygen centered free radical formation by the stable prostacyclin-mimetic Iloprost (ZK 36 374) in acute myocardial ischemia. J Cardiovasc Pharmacol 6: 365–366

    Article  PubMed  CAS  Google Scholar 

  54. Ward PA, Till GO, Kunkel R, Beauchamp C (1983) Evidence for role of hydroxyl radical in compliment and neutrophil dependent tissue injury. J Clin Invest 72: 789–801

    Article  PubMed  CAS  Google Scholar 

  55. Werns SW, Shea MJ, Driscoll EM, Cohen C, Abrams GD, Pitt B, Lucchesi BR (1985) The independent effects of oxygen radical scavengers on canine infarct size. Reduction by superoxide dismutase and not catalase. Circ Res 56: 895–898

    PubMed  CAS  Google Scholar 

  56. Werns SW, Shea MJ, Lucchesi BR (1985) Free radicals in ischemic myocardial injury. J Free Radicals Biol Med 1: 103–110

    Article  CAS  Google Scholar 

  57. Wildenthal K (1978) Lysosomal alterations in ischemic myocardium: results or cause of myocellular damage? J Mol Cell Cardiol 10: 595–603

    Article  PubMed  CAS  Google Scholar 

  58. Wildenthal K, Decker RS, Poole AR, Griffin EE, Dingle JT (1978) Sequential lysosomal alterations during cardiac ischemia. I. Biochemical and immunohistochemical changes. Lab Invest 38: 656–661

    PubMed  CAS  Google Scholar 

  59. Zurier RB, Quagliata F (1971) Effects of prostaglandin El on adjuvant arthritis. Nature 234: 304

    Article  PubMed  CAS  Google Scholar 

  60. Zurier RB, Damjanou I, Sayadoff DM, Rothfield N (1979) Prostaglandin Bu treatment of NZB/NZW Fi hybrid mice. II. Prevention of glomerulonephritis. Arthritis Rheum 20: 1449

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical School, Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan, USA

    P. J. Simpson & B. R. Lucchesi

Authors
  1. P. J. Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. R. Lucchesi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Copernicus Academy of Medicine, 16 Grzegórzecka, 31531, Cracow, Poland

    R. J. Gryglewski

  2. Cardiovascular Pharmacology, Schering AG, Müllerstraße 170–178, 1000, Berlin 65, Germany

    G. Stock

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Springer-Verlag, Berlin Heidelberg

About this paper

Cite this paper

Simpson, P.J., Lucchesi, B.R. (1987). Myocardial Ischemia: The Potential Therapeutic Role of Prostacyclin and Its Analogues. In: Gryglewski, R.J., Stock, G. (eds) Prostacyclin and Its Stable Analogue Iloprost. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71499-3_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71499-3_20

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71501-3

  • Online ISBN: 978-3-642-71499-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation