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Clinical Cardiology logoLink to Clinical Cardiology
. 2009 Feb 3;23(11):837–841. doi: 10.1002/clc.4960231110

Isosorbide dinitrate inhibits platelet adhesion and aggregation in nonthrombolyzed patients with acute myocardial infarction

Jadwiga Gebalska 1,, Robert Wolk 1, Leszek Ceremuzynski 1
PMCID: PMC6654871  PMID: 11097131

Abstract

Background: Apart from their vasodilatator properties, nitrates have been shown to inhibit platelet aggregation. The effects of nitrates on platelet adhesion have not been studied. Nonselected patients with acute myocardial infarction (AMI) have been suggested to gain no benefit from administration of nitrates. However, the importance of nitrates may be greater in a subgroup of nonthrombolyzed patients with AMI.

Hypothesis: Isosorbide dinitrate (ISDN) decreases platelet adhesion and aggregation in nonthrombolyzed patients with AMI.

Methods: Consecutive 48 men with AMI, not eligible for thrombolytic therapy because of late presentation (> 12 h), were prospectively randomized 2:1 to double‐blind ISDN (mean dose 2.4 ± 0.9 mg/h) (n = 33) or placebo (0.9% sodium chloride) (n = 15) infusion. All patients received aspirin. Blood samples were taken at baseline (no study medication) and 3 h into ISDN or placebo infusion. Platelet adhesion to collagen was measured in the ethylene diamine tetraacetic acid (EDTA)‐platelet rich plasma by recording changes in light transmission with an optical aggregometer. Platelet aggregation was measured using the Born's method.

Results: Isosorbide dinitrate significantly decreased both platelet adhesion and aggregation. No effect was seen in the placebo group.

Conclusions: In patients with AMI who do not receive thrombolytic therapy, ISDN effectively inhibits platelet adhesion and aggregation. These effects of nitrates may be of therapeutic and prognostic significance in this group of patients.

Keywords: isosorbide dinitrate, myocardial infarction, platelets, adhesion, aggregation

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References

  • 1. Furlong B, Henderson AH, Lewis MJ, Smith JA: Endothelium‐derived relaxing factor inhibits in vitro platelet aggregation. Br J Pharmacol 1987; 90: 687–692 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Radomski MW, Palmer RMJ, Moncada S: Comparative pharmacology of endothelium‐derived relaxing factor, nitric oxide and prostaglandin in platelets. Br J Pharmacol 1987; 92: 181–187 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Radomski MW, Moncada S: Regulation of vascular homeostasis by nitric oxide. Thromb Haemost 1993; 70: 36–41 [PubMed] [Google Scholar]
  • 4. Radomski MW, Palmer RMJ, Moncada S: Endogenous nitric oxide inhibits platelet adhesion to vascular endothelium. Lancet 1987; 2: 1057–1058 [DOI] [PubMed] [Google Scholar]
  • 5. de Graaf JC, Banga JD, Moncada S, Palmer RM, de Groot PG, Sixma JJ: Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation 1992; 85: 2284–2290 [DOI] [PubMed] [Google Scholar]
  • 6. Schafer AI, Alexander RW, Handin RI: Inhibition of platelet function by organic nitrate vasodilators. Blood 1980; 55: 649–654 [PubMed] [Google Scholar]
  • 7. De Caterina R: Antiplatelet effects of nitrates. Thromb Haemorrh Disord 1990; 2: 61–68 [Google Scholar]
  • 8. Weber AA, Strobach H, Schror K: Direct inhibition of platelet function by organic nitrates via nitric oxide formation. Eur J Pharmacol 1993; 247: 29–37 [DOI] [PubMed] [Google Scholar]
  • 9. Drummer C, Valta‐Senfzer U, Karrenbrock B, Heim JM, Gerzer R: Comparison of antiplatelet properties of molsidomine, isosorbide‐5‐mononitrate and placebo in healthy volunteers. Eur Heart J 1991; 12: 541–549 [DOI] [PubMed] [Google Scholar]
  • 10. Chirkov YY, Naujalis JI, Sage RE, Horowitz JD: Antiplatelet effects of nitroglycerin in healthy subjects and in patients with stable angina pectoris. J Cardiovasc Pharmacol 1993; 21: 384–389 [DOI] [PubMed] [Google Scholar]
  • 11. De Caterina R, Giannessi D, Bernini W, Mazzone A: Organic nitrates: Direct antiplatelet effects and synergism with prostacyclin. Antiplatelet effects of organic nitrates. Thromb Haemost 1988; 59: 207–211 [PubMed] [Google Scholar]
  • 12. Stamler J, Cunningham M, Loscalzo J: Reduced thiols and the effect of intravenous nitroglycerin on platelet aggregation. Am J Cardiol 1988; 62: 377–380 [DOI] [PubMed] [Google Scholar]
  • 13. Sizinger H, Virgolini I, O'Grady J, Rauscha F, Fitscha P: Modification of platelet function by isosorbide dinitrate in patients with coronary artery disease. Thromb Res 1992; 65: 323–335 [DOI] [PubMed] [Google Scholar]
  • 14. Langford EJ, Wainwright RJ, Martin JF: Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors. Arterioscler Thromb Vase Biol 1996; 16: 51–55 [DOI] [PubMed] [Google Scholar]
  • 15. Diodati J, Théroux P, Latour JG, Lacoste L, Lam JYT, Waters D: Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction. Am J Cardiol 1990; 66: 683–688 [DOI] [PubMed] [Google Scholar]
  • 16. Sizinger H, Fitscha P, O'Grady J, Rauscha F, Rogatti W, Vane JR: Synergistic effect of prostaglandin E1 and isosorbide dinitrate in peripheral vascular disease. Lancet 1990; 335: 627–628 [DOI] [PubMed] [Google Scholar]
  • 17. Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico. GISSI‐3 : Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6‐week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115–1122 [PubMed] [Google Scholar]
  • 18. ISIS‐4 : A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS‐4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 1995; 345: 669–685 [PubMed] [Google Scholar]
  • 19. Fitzgerald DJ, Catella F, Roy L, Fitzgerald GA: Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988; 77: 142–150 [DOI] [PubMed] [Google Scholar]
  • 20. Bertolino G, Noris P, Previtali M, Gamba G, Ferrario M, Montani N, Balduini CL: Platelet function after in vivo and in vitro treatment with thrombolytic agents. Am J Cardiol 1992; 69: 457–461 [DOI] [PubMed] [Google Scholar]
  • 21. Karlberg KE, Chen J, Hagerman I, Bergstrom K, Wallin R, Saldeen T, Sylven C: Streptokinase, but not tissue plasminogen activator, attenuates platelet aggregation in patients with acute myocardial infarction. J Intent Med 1993; 234: 513–519 [DOI] [PubMed] [Google Scholar]
  • 22. Frandsen NJ, Winther K, Pedersen F, Christiansen I, McNair P: Time course of platelet alpha granule release in acute myocardial infarction treated with streptokinase. Heart 1996; 75: 141–144 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Born GVR, Cross MJ: The aggregation of blood platelets. J Physiol (London) 1963; 168: 178–195 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Karlberg KE, Torfgard K, Ahlner J, Sylven C: Dose‐dependent effect of intravenous nitroglycerin on platelet aggregation, and correlation with plasma glyceryl dinitrate concentration in healthy men. Am J Cardiol 1992; 69: 802–805 [DOI] [PubMed] [Google Scholar]
  • 25. Wolfram G, Meyer U, Scheske U, Horn M, Drummer C, Spannagl M, Gerzer R: Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man. Eur J Med Res 1996; 1: 291–298 [PubMed] [Google Scholar]
  • 26. De Caterina R, Giannessi D, Crea F, Chierchia S, Bernini W, Gazzetti P, L'Abbate A: Inhibition of platelet function by injectable isosorbide dinitrate. Am J Cardiol 1984; 53: 1683–1687 [DOI] [PubMed] [Google Scholar]
  • 27. Anfossi G, Massucco P, Piretto V, Mularoni E, Cavalot F, Mattiello L, Trovati M: Glyceryl trinitrate enhances the adenosine‐induced inhibition of platelet responses: A mechanism potentially involved in the in vivo anti‐aggregating effects of organic nitrates. Clin Exp Pharmacol Physiol 1995; 22: 803–811 [DOI] [PubMed] [Google Scholar]
  • 28. Yoshimoto H, Suehiro A, Higasa S, Seto T, Oku KI, Kakishita E: Inhibitory effect of isosorbide dinitrate on whole blood aggregation. J Cardiol 1997; 29: 195–201 [PubMed] [Google Scholar]
  • 29. Yoshimoto H, Suehiro A, Kakishita E: Exogenous nitric oxide inhibits platelet activation in whole blood. J Cardiovasc Pharmacol 1999; 33: 109–115 [DOI] [PubMed] [Google Scholar]
  • 30. Radomski MW, Palmer RMJ, Moncada S: The antiaggregating properties of vascular endothelium: Interaction between prostacyclin and nitric oxide. Br J Pharmacol 1987: 92: 639–646 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Radomski MW, Palmer RM, Moncada S: The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 1987; 148: 1482–1489 [DOI] [PubMed] [Google Scholar]
  • 32. Groves PH, Penny WJ, Cheadle HA, Lewis MJ: Exogenous nitric oxide inhibits in vivo platelet adhesion following balloon angioplasty. Cardiovasc Res 1992; 26: 615–619 [DOI] [PubMed] [Google Scholar]
  • 33. Wu CC, Ko FN, Teng CM: Inhibition of platelet adhesion to collagen by cGMP‐elevating agents. Biochem Biophys Res Commun 1997; 231: 412–416 [DOI] [PubMed] [Google Scholar]
  • 34. Patrono C: Aspirin and human platelets: From clinical trials to acetylation of cyclooxygenase and back. TIPS 1989; 10: 453–458 [DOI] [PubMed] [Google Scholar]
  • 35. Speat TH, Lejnicks I: A technique for estimation of platelet‐collagen adhesion. Proc Soc Exp Biol Med 1996; 132: 1038–1040 [DOI] [PubMed] [Google Scholar]
  • 36. Garcia‐Dorado D, Permanyer‐Miralda G, Brotons C, Calvo F, Camprecios M, Oliveras J, Santos MT, Moral I, Soler‐Soler J: Attenuated severity of new acute ischemic events in patients with previous coronary heart disease receiving long‐acting nitrates. Clin Cardiol 1999; 22: 303–308 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Sylven C, Karlberg KE, Chen J, Hagerman I, Egberg N, Bergstrom K: Enhanced platelet function in acute myocardial infarction is attenuated by streptokinase treatment. J Intern Med 1992; 231: 595–600 [DOI] [PubMed] [Google Scholar]
  • 38. Mehta P, Mehta J: Platelet function studies in coronary artery disease. V. Evidence for enhanced platelet microthrombus formation activity in acute myocardial infarction. Am J Cardiol 1979; 43: 757–760 [DOI] [PubMed] [Google Scholar]
  • 39. Fuchs J, Weinberger I, Rotenberg Z, Joshua H, Almozlino A, Agmon J: Circulating aggregated platelets in coronary artery disease. Am J Cardiol 1987; 60: 534–537 [DOI] [PubMed] [Google Scholar]
  • 40. Frink RJ, Rooney PA Jr, Trowbridge JO, Rose JP: Coronary thrombosis and platelet/fibrin microemboli in death associated with acute myocardial infarction. Br Heart J 1988; 59: 196–200 [DOI] [PMC free article] [PubMed] [Google Scholar]

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