Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1994 Jul;38(1):63–70. doi: 10.1111/j.1365-2125.1994.tb04323.x

Effects of treatment with oral isosorbide dinitrate on platelet function in vivo; a double-blind placebo-controlled study in patients with stable angina pectoris.

N H Wallén 1, A Andersson 1, P Hjemdahl 1
PMCID: PMC1364839  PMID: 7946939

Abstract

1. A randomised double-blind placebo-controlled cross-over study was performed to investigate the effects of oral isosorbide dinitrate (ISDN; 20 mg twice daily for 2 weeks) on various aspects of platelet function in vivo in 20 patients with stable angina pectoris. Measurements were performed at rest and after platelet activation by physical exercise (bicycle ergometry). 2. Compared with placebo, treatment with ISDN significantly decreased systolic blood pressure at rest by 7 (-14 to -1) mm Hg (mean and 95% CI) and tended to increase exercise capacity by 7 (-1 to 14) W and attenuate perceived chest pain during maximal work. The dosage was high, as judged by side-effects reported (mainly headache). Compliance was good, as assessed by electronic counter equipped tablet bottles (Medication Event Monitoring System); only one patient had a compliance rate below 60%. 3. Exercise significantly increased platelet aggregability as measured by filtragometry ex vivo; the time taken for platelet aggregates in whole blood drawn directly from an antecubital vein to occlude a microfilter was significantly decreased from 155 to 95 s (antilog of mean log values). Platelet secretion in vivo also increased, as indicated by significant elevations of beta-thromboglobulin in plasma; from 22 to 35 ng ml-1 (P = 0.006). 4. ISDN treatment did not inhibit platelet function. Relative to placebo, filtragometry readings (ISDN/placebo ratios; mean and 95% CI) were not altered either at rest (1.05 (0.83 to 1.32)) or immediately after exercise (0.98 (0.80 to 1.20)). Similarly, beta TG in plasma was unaltered by ISDN treatment; 1.09 (0.98 to 1.21) at rest, and 1.04 (0.82 to 1.30) immediately after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
63

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beck O., Wallén N. H., Bröijersén A., Larsson P. T., Hjemdahl P. On the accurate determination of serotonin in human plasma. Biochem Biophys Res Commun. 1993 Oct 15;196(1):260–266. doi: 10.1006/bbrc.1993.2243. [DOI] [PubMed] [Google Scholar]
  2. Benson H., McCallie D. P., Jr Angina pectoris and the placebo effect. N Engl J Med. 1979 Jun 21;300(25):1424–1429. doi: 10.1056/NEJM197906213002508. [DOI] [PubMed] [Google Scholar]
  3. Brezinski D. A., Tofler G. H., Muller J. E., Pohjola-Sintonen S., Willich S. N., Schafer A. I., Czeisler C. A., Williams G. H. Morning increase in platelet aggregability. Association with assumption of the upright posture. Circulation. 1988 Jul;78(1):35–40. doi: 10.1161/01.cir.78.1.35. [DOI] [PubMed] [Google Scholar]
  4. Chamberlain K. G., Tong M., Penington D. G. Properties of the exchangeable splenic platelets released into the circulation during exercise-induced thrombocytosis. Am J Hematol. 1990 Jul;34(3):161–168. doi: 10.1002/ajh.2830340302. [DOI] [PubMed] [Google Scholar]
  5. Chirkov Y. Y., Naujalis J. I., Sage R. E., Horowitz J. D. Antiplatelet effects of nitroglycerin in healthy subjects and in patients with stable angina pectoris. J Cardiovasc Pharmacol. 1993 Mar;21(3):384–389. doi: 10.1097/00005344-199303000-00006. [DOI] [PubMed] [Google Scholar]
  6. Cramer J. A., Mattson R. H., Prevey M. L., Scheyer R. D., Ouellette V. L. How often is medication taken as prescribed? A novel assessment technique. JAMA. 1989 Jun 9;261(22):3273–3277. [PubMed] [Google Scholar]
  7. Davì G., Cannizzaro S., Giubilato A., Novo S., Mattina A., Strano A. Enhanced platelet sensitivity to prostacyclin after isosorbide-5-mononitrate in patients with stable angina pectoris. Z Kardiol. 1986;75 (Suppl 3):80–82. [PubMed] [Google Scholar]
  8. 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 Jun 1;53(11):1683–1687. doi: 10.1016/0002-9149(84)90602-7. [DOI] [PubMed] [Google Scholar]
  9. Diodati J., Théroux P., Latour J. G., Lacoste L., Lam J. Y., Waters D. Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction. Am J Cardiol. 1990 Sep 15;66(7):683–688. doi: 10.1016/0002-9149(90)91130-x. [DOI] [PubMed] [Google Scholar]
  10. Fitzgerald D. J., Roy L., Robertson R. M., FitzGerald G. A. The effects of organic nitrates on prostacyclin biosynthesis and platelet function in humans. Circulation. 1984 Aug;70(2):297–302. doi: 10.1161/01.cir.70.2.297. [DOI] [PubMed] [Google Scholar]
  11. Fuster V., Badimon L., Badimon J. J., Chesebro J. H. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med. 1992 Jan 23;326(4):242–250. doi: 10.1056/NEJM199201233260406. [DOI] [PubMed] [Google Scholar]
  12. Förstermann U., Mügge A., Alheid U., Haverich A., Frölich J. C. Selective attenuation of endothelium-mediated vasodilation in atherosclerotic human coronary arteries. Circ Res. 1988 Feb;62(2):185–190. doi: 10.1161/01.res.62.2.185. [DOI] [PubMed] [Google Scholar]
  13. Gerzer R., Drummer C., Karrenbrock B., Heim J. M. Inhibition of platelet activating factor-induced platelet aggregation by molsidomine, SIN-1, and nitrates in vitro and ex vivo. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S115–S119. [PubMed] [Google Scholar]
  14. Hjemdahl P., Perneby C., Theodorsson E., Egberg N., Larsson P. T. A new assay for beta-thromboglobulin in urine. Thromb Res. 1991 Oct 1;64(1):33–43. doi: 10.1016/0049-3848(91)90203-9. [DOI] [PubMed] [Google Scholar]
  15. Hogan J. C., Lewis M. J., Henderson A. H. Glyceryl trinitrate and platelet aggregation: effects of N-acetyl-cysteine. Br J Clin Pharmacol. 1989 May;27(5):617–619. doi: 10.1111/j.1365-2125.1989.tb03425.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hornstra G., ten Hoor F. The filtragometer: a new device for measuring platelet aggregation in venous blood of man. Thromb Diath Haemorrh. 1975 Nov 15;34(2):531–544. [PubMed] [Google Scholar]
  17. Jensen P. N., Glud T. K., Arnfred T. Platelet number and platelet volume in healthy young men during exercise and changes in posture. Scand J Clin Lab Invest. 1984 Dec;44(8):735–738. doi: 10.3109/00365518409083637. [DOI] [PubMed] [Google Scholar]
  18. Karlberg K. E., Torfgård K., Ahlner J., Sylvén C. Dose-dependent effect of intravenous nitroglycerin on platelet aggregation, and correlation with plasma glyceryl dinitrate concentration in healthy men. Am J Cardiol. 1992 Mar 15;69(8):802–805. doi: 10.1016/0002-9149(92)90509-w. [DOI] [PubMed] [Google Scholar]
  19. Kestin A. S., Ellis P. A., Barnard M. R., Errichetti A., Rosner B. A., Michelson A. D. Effect of strenuous exercise on platelet activation state and reactivity. Circulation. 1993 Oct;88(4 Pt 1):1502–1511. doi: 10.1161/01.cir.88.4.1502. [DOI] [PubMed] [Google Scholar]
  20. Larsson P. T., Hjemdahl P., Olsson G., Egberg N., Hornstra G. Altered platelet function during mental stress and adrenaline infusion in humans: evidence for an increased aggregability in vivo as measured by filtragometry. Clin Sci (Lond) 1989 Apr;76(4):369–376. doi: 10.1042/cs0760369. [DOI] [PubMed] [Google Scholar]
  21. Ludmer P. L., Selwyn A. P., Shook T. L., Wayne R. R., Mudge G. H., Alexander R. W., Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986 Oct 23;315(17):1046–1051. doi: 10.1056/NEJM198610233151702. [DOI] [PubMed] [Google Scholar]
  22. Martin J. F., Bath P. M., Burr M. L. Influence of platelet size on outcome after myocardial infarction. Lancet. 1991 Dec 7;338(8780):1409–1411. doi: 10.1016/0140-6736(91)92719-i. [DOI] [PubMed] [Google Scholar]
  23. Masuhara M., Kami K., Umebayashi K., Tatsumi N. Effect of strenuous exercise on platelet. J Sports Med Phys Fitness. 1987 Jun;27(2):178–183. [PubMed] [Google Scholar]
  24. Mehta J., Mehta P. Comparative effects of nitroprusside and nitroglycerin on platelet aggregation in patients with heart failure. J Cardiovasc Pharmacol. 1980 Jan-Feb;2(1):25–33. doi: 10.1097/00005344-198001000-00004. [DOI] [PubMed] [Google Scholar]
  25. Naesh O., Hindberg I., Trap-Jensen J., Lund J. O. Post-exercise platelet activation--aggregation and release in relation to dynamic exercise. Clin Physiol. 1990 May;10(3):221–230. doi: 10.1111/j.1475-097x.1990.tb00090.x. [DOI] [PubMed] [Google Scholar]
  26. Peatfield R. C., Gawel M. J., Clifford-Rose F., Guthrie D. L., Pearson T. C. The effects of exercise on platelet numbers and size. Med Lab Sci. 1985 Jan;42(1):40–43. [PubMed] [Google Scholar]
  27. Sinzinger 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 Feb 1;65(3):323–335. doi: 10.1016/0049-3848(92)90163-5. [DOI] [PubMed] [Google Scholar]
  28. Stamler J. S., Loscalzo J. The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders. J Am Coll Cardiol. 1991 Nov 15;18(6):1529–1536. doi: 10.1016/0735-1097(91)90686-4. [DOI] [PubMed] [Google Scholar]
  29. Vane J. R., Anggård E. E., Botting R. M. Regulatory functions of the vascular endothelium. N Engl J Med. 1990 Jul 5;323(1):27–36. doi: 10.1056/NEJM199007053230106. [DOI] [PubMed] [Google Scholar]
  30. Wadenvik H., Kutti J. The spleen and pooling of blood cells. Eur J Haematol. 1988 Jul;41(1):1–5. doi: 10.1111/j.1600-0609.1988.tb00861.x. [DOI] [PubMed] [Google Scholar]
  31. Wallén N. H., Larsson P. T., Bröijersén A., Andersson A., Hjemdahl P. Effects of an oral dose of isosorbide dinitrate on platelet function and fibrinolysis in healthy volunteers. Br J Clin Pharmacol. 1993 Feb;35(2):143–151. doi: 10.1111/j.1365-2125.1993.tb05680.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Willich S. N., Maclure M., Mittleman M., Arntz H. R., Muller J. E. Sudden cardiac death. Support for a role of triggering in causation. Circulation. 1993 May;87(5):1442–1450. doi: 10.1161/01.cir.87.5.1442. [DOI] [PubMed] [Google Scholar]
  33. Wiman B., Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease. Semin Thromb Hemost. 1990 Jul;16(3):207–216. doi: 10.1055/s-2007-1002671. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES