Effects of Cigarette Smoke and Nicotine on Platelets and Experimental Coronary Artery Thrombosis

  • J. D. Folts
  • S. A. Gering
  • S. W. Laibly
  • B. G. Bertha
  • F. C. Bonebrake
  • J. W. Keller
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 273)


The first study linking smoking with predicted risk of cardiovascular disease was published in 1958 (1), and this has been confirmed by numerous epidemiologic studies from around the world. The major forms of coronary artery disease and peripheral vascular disease associated with smoking are the result of progressive development of atherosclerosis. Atherosclerotic plaques and fatty streaks can occur early in life as shown in the Korean war autopsy studies in 1953 (2), and confirmed by several other studies (3,4). By some unknown mechanism smoking appears to accelerate the development of the atherosclerotic process.


Coronary Artery Platelet Aggregation Arterial Blood Pressure Platelet Activity Platelet Rich Plasma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    E. C. Hammond, and D. Horn, Smoking and death rates—report on forty-four months of follow-up of 187,783 men. II. Death rates by cause, JAMA. 166:1294–308 (1958).CrossRefGoogle Scholar
  2. 2.
    W. F. Enos, R. H. Holmes, and J. Beyer, Coronary disease among united States soldiers killed in action in Korea, JAMA. 152:1090–3 1953.CrossRefGoogle Scholar
  3. 3.
    J. P. Strong, and H. C. McGill Jr., The natural history of coronary atherosclerosis, Am J Pathol. 40:37–49 (1962).PubMedGoogle Scholar
  4. 4.
    C. Tejada, J. P. Strong, M. R. Montenegro, C. Restrepo, and L. A. Solberg, Distribution of coronary and aortic atherosclerosis by geographic location, race and sex, Lab Invest. 18:509–26 (1968).PubMedGoogle Scholar
  5. 5.
    J. L. Gordon and A. J. Milner, Blood platelets as multifunctional cells, in: ‘Platelets in biology and pathology,’ Gordon, ed., Elsevier/North-Holland Biomedical Press, Cambridge, England (1976).Google Scholar
  6. 6.
    P. F. Davies, Biology of disease. Vascular cell interactions with special reference to the pathogenesis of atherosclerosis, Lab Invest. 55:5–24 (1986).PubMedGoogle Scholar
  7. 7.
    V. Fuster, J. T. Lie, L. Badimon, J. A. Rosemark, and W. Bowie, Spontaneous and diet induced coronary atherosclerosis in normal swine and swine with Von Willibrands disease, Arteriosclerosis., 5(l):67–73 (1985).PubMedGoogle Scholar
  8. 8.
    R. Ross, The pathogenesis of atherosclerosis — an update, N Engl J Med. 314(8):488–500 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    K. S. McCully, Homocysteine theory of arteriosclerosis: development and current status, in: ‘Atherosclerosis review’, A. M. Gotto, R. Paoletti, eds., Raven Press, New York (1983).Google Scholar
  10. 10.
    S. Renaud, D. Blache, E. Dumont, T. Thevenan, and T. Wissendanger, Platelet function after cigarette smoking in relation to nicotine and carbon monoxide, Clin Pharmacol Ther. 36:389–95 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    G. A. FizGerald, J. A. Oates, and J. Nowak, Cigarette smoking and hemostatic function, Am Heart J. 115:267 (1988).CrossRefGoogle Scholar
  12. 12.
    J. D. Folts, and F. C. Bonebrake, The effects of cigarette smoke and nicotine on platelet plugging in stenosed dog coronary arteries: inhibition with phentolamine, Circulation. 65(3):465–9 (1982).PubMedCrossRefGoogle Scholar
  13. 13.
    J. F. Mustard, Effect of smoking on blood coagulation and platelet survival in man, Br Med J. 1:846–9 (1963).PubMedCrossRefGoogle Scholar
  14. 14.
    V. Fuster, J. H. Chesboro, R. Frye, and L. R. Elveback, Platelet survival and the development of coronary artery disease in the young adult: effects of cigarette smoking, strong family history and medical therapy, Circulation. 63:546–51 (1983).CrossRefGoogle Scholar
  15. 15.
    G. A. FitzGerald, A. K. Pedesen, and C. Patrono, Analysis of prostacyclin and thromboxane A2 biosynthesis in cardiovascular disease [Editorial], Circulation. 67:1174–7 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    J. D. Folts, E. B. Crowell, and G. G. Rowe, Platelet aggregation in partially obstructed vessels and their elimination with aspirin, Circulation. 54:365–70 (1976).PubMedGoogle Scholar
  17. 17.
    R. Bolli, Ware J. A. Brandon T. A., D. G. Willacher, and M. L. Mace, Platelet mediated thrombosis in stenosed canine coronary arteries: Inhibition by a platelet-active alpha-adrenergic antagonist, JACC. 3(6):1417–26 (1984).PubMedGoogle Scholar
  18. 18.
    J. H. Ashton, J. M. Schmitz, W. B. Campbell, C. Fitzgerald, L. M. Buja, and J. T. Willerson, Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists, Circ Res. 59(5):568–78 (1986).PubMedGoogle Scholar
  19. 19.
    P. Golino, M. Buja, J. H. Ashton, P. Kulkarni, A. Taylor, and J. T. Willerson, Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary arteries, Circulation. 78:701–11 (1988).PubMedCrossRefGoogle Scholar
  20. 20.
    B. G. Bertha, and J.D. Folts, Inhibition of epinephrine exacerbated coronary thrombus formation by PGI2 in the dog, J Lab Clin Med. 103(2):204–14 (1984).PubMedGoogle Scholar
  21. 21.
    J. T. Strony, J. D. Folts, and B. Adelman, In vivo antiplatelet effect of gly-arg-gly-asp-ser in the stenosed canine coronary artery occlusion model, Clin Res. 37(2):388A (1989).Google Scholar
  22. 22.
    J. D. Folts, J. Stamler, and J. Loscalzo, N-acetylcysteine potentiates i.v. nitroglycerin in inhibiting periodic platelet thrombus formation in stenosed dog coronary arteries, JACC. 13(2):145A (1989).Google Scholar
  23. 23.
    J. D. Folts, Experimental arterial platelet thrombosis, platelet inhibitors, and their possible clinical relevance, Cardiovasc Rev Rep. 3(3):370–82 (1982).Google Scholar
  24. 24.
    J. D. Folts, and G. G. Rowe, Epinephrine reverses aspirin inhibition of in vivo platelet thrombus formation in stenosed dog coronary arteries, Thromb Res 50:507–16 (1988).PubMedCrossRefGoogle Scholar
  25. 25.
    J. D. Folts. D. Detmer, and R. Nadler, Possible acute platelet thrombus formation in dog and human femoral arteries, Texas Heart Institute J. 9:12–26 (1982).Google Scholar
  26. 26.
    E. Eichhorn, P. A. Grayburn, H. V. Anderson, J. B. Bedotto, M. M. Carry, and J. T. Willerson, Cyclic coronary artery flow variations before and after percutaneous transluminal coronary angioplasty in man, Circulation. (Suppl II) 80(4):371 (1989).Google Scholar
  27. 27.
    V. Fuster, J. H. Chesebro, R. L. Frye, and L. R. Elveback, Platelet survival and the development of coronary artery disease in the young adult: effects of cigarette smoking, strong family history and medical therapy, Circulation 63:546–51 (1981).PubMedCrossRefGoogle Scholar
  28. 28.
    J. Barboriak, A. J. Anderson, R. G. Hoffmann, Smoking, alcohol and coronary artery occlusion, Atherosclerosis. 43:277–82 (1982).PubMedCrossRefGoogle Scholar
  29. 29.
    D. J. Kozarorevic, N. Vojvodic, and T. Dawber, Frequency of alcohol consumption and morbidity and mortality, Lancet, I:613–6 (1980).CrossRefGoogle Scholar
  30. 30.
    M. G. Marmot, M. J. Shipley, G. Rose, and B. J. Thomas, Alcohol and mortality: a U-shaped curve, Lancet. I:580–3 (1981).CrossRefGoogle Scholar
  31. 31.
    K. Yano, G. G. Rhoads, and A. Kagan, Coffee, alcohol and risk of coronary heart disease among Japanese men living in Hawaii, N Engl J Med. 297:405–9 (1977).PubMedCrossRefGoogle Scholar
  32. 32.
    J. J. Barboriak, A. J. Anderson, and R. G. Hoffmann, Interrelationship between coronary artery occlusion, high-density lipoprotein cholesterol, and alcohol intake, J Lab Clin Med. 94:348–53 (1979).PubMedGoogle Scholar
  33. 33.
    P. H. Levine, An acute effect of cigarette smoking on platelet function-A possible link between smoking and arterial thrombosis, Circulation. 48:619–23 (1973).PubMedGoogle Scholar
  34. 34.
    R. I. Hawkens, Smoking, platelets, and thrombosis, Nature.236:450–2 (1972).CrossRefGoogle Scholar
  35. 35.
    J. W. Davis, and P. E. Phillips, The effect of ethanol on human platelet aggregation in vitro, Atherosclerosis. 11:473–7 (1970).PubMedCrossRefGoogle Scholar
  36. 36.
    D. H. Cowman, The platelet defect in alcoholism. Ann NY Acad Sci 1975; 252:328–41.CrossRefGoogle Scholar
  37. 37.
    C. G. Fenn, and J. M. Littleton, Inhibition of platelet aggregation by ethanol in vitro shows specificity for aggregating agent used and is influenced by platelet lipid composition, Thromb Haemostas. 48:49–53 (1982).Google Scholar
  38. 38.
    J. W. Keller, M. Saltzberg, and J. D. Folts, Synergistic inhibitor effects of aspirin and ethanol on epinephrine exacerbation of acute platelet thrombus formation in stenosed canine coronary arteries, Cardiovasc Res. (in press).Google Scholar
  39. 39.
    J. Ayers, C. F. Ruff, and D. I. Templer, Alcoholism, cigarette smoking, coffee drinking and extraversion, J. Stud Alcohol. 37:983–5 (1976).PubMedGoogle Scholar
  40. 40.
    P. M. Moody, Drinking and smoking behavior of hospitalized medical patients, J Stud Alcohol. 37:1316–9 (1976).PubMedGoogle Scholar
  41. 41.
    R. O. Cummins, A. G. Shaper, M. Walker, and C. J. Wale, Smoking and drinking by middle aged British men: effects of social class and town of residence, Br Med J. 283:1497–502 (1981).CrossRefGoogle Scholar
  42. 42.
    R. R. Griffiths, G. E. Bigelow, and I. Liebson, Facilitation of human tobacco self-administration by ethanol: a behavioral analysis, J Exp Anal Behav 25:279–92 (1976).PubMedCrossRefGoogle Scholar
  43. 43.
    N. K. Mello, J. H. Mendelson, M. L.Sellers, and J. L. Kuehnle, Effect of alcohol and marijuana on tobacco smoking, Clin Pharmacol Ther. 27:202–9 (1980).PubMedCrossRefGoogle Scholar
  44. 44.
    E. Wynder and D. Hoffman, Some characteristics of tobacco smoke, in: ‘Tobacco and tobacco smoke’, Academic Press, New York (1976).Google Scholar
  45. 45.
    G. H. R. Rao, G, Escolar, and J. G. White, Epinephrine reverses the inhibitory influence of aspirin on platelet-vessel wall interactions, Thromb Res. 44:65–74 (1986).PubMedCrossRefGoogle Scholar
  46. 46.
    D. H. Cowan, Effect of alcoholism in hemostasis, Semin Hematol. 17:137–47 (1980).PubMedGoogle Scholar
  47. 47.
    M. B. Feinstein, J. Fiekers, and C. Fraser, An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion, J Pharmacol Exp Ther. 197:215–28 (1976).PubMedGoogle Scholar
  48. 48.
    H. McGill, Potential mechanisms for the augmentation of atherosclerosis and atherosclerotic disease by cigarette smoking, Prev Med. 8:390–403 (1979).PubMedCrossRefGoogle Scholar
  49. 49.
    J. W. Keller, and J. D. Folts, Relative effects of cigarette smoke and ethanol on acute platelet canine coronary arteries, Cardiovasc Res. 22(l):73–8 (1988).PubMedCrossRefGoogle Scholar
  50. 50.
    A. Kershbaum, and S. Bellet, Cigarette smoking and blood lipids, JAMA. 187(1):32–6 (1964).PubMedCrossRefGoogle Scholar
  51. 51.
    D. T. Watts, The effects of nicotine and smoking on the secretion of epinephrine, Ann NY Acad Sci. 90:74–80 (1960).PubMedCrossRefGoogle Scholar
  52. 52.
    J. Trap-Jensen, Effects of smoking on the heart and peripheral circulation, Am Heart J. 115:263–7 (1988).PubMedCrossRefGoogle Scholar
  53. 53.
    G. Grignani, G. Gamba, and E. Ascari, Cigarette-smoking effect on platelet function, Thrombos Haemostas. 37:223–8 (1977).Google Scholar
  54. 54.
    P. Hill, Effects of nicotine on the serum epinephrine and cor-ticoids, Am Heart J. 87(4):491–6 (1974).PubMedCrossRefGoogle Scholar
  55. 55.
    S. R. Saba, and R. G. Mason. Some effects of nicotine on platelets, Thromb Res. 7:819–24 (1975).PubMedCrossRefGoogle Scholar
  56. 56.
    A. Wennmalm, Interaction of nicotine and prostaglandins in the cardiovascular system, Prostaglandins. 23:139–45 (1982).PubMedCrossRefGoogle Scholar
  57. 57.
    A. Wennmalm, and P. Alster, Nicotine inhibits vascular prostacyclin but not platelet thromboxane formation, Gen Pharmacol. 14:189–91 (1983).PubMedGoogle Scholar
  58. 58.
    H. Madsen, and J. Dyerberg, Cigarette smoking and its effects on the platelet-vessel wall interaction, Scand J Clin Lab Invest. 44:203–6 (1984).PubMedCrossRefGoogle Scholar
  59. 59.
    A. Boura, S. Hui, and W. Walters, Cigarette smoke inhalation specifically inhibits depressor responses to prostacyclin in the rat, Br J Pharmacol. 73:3 (1981).PubMedGoogle Scholar
  60. 60.
    R. M. Pittilo, J. M. Clark, D. Harris, I. J. Mackie, P. M. Rowles, S. J. Machin, and N. Woolf, Cigarette smoking and platelet adhesion, Br J Haematol. 58:627–32 (1984).PubMedCrossRefGoogle Scholar
  61. 61.
    H. Sinzinger, and A. Kefalides, Passive smoking severely decreases platelet sensitivity to antiaggregating prostaglandins, Lancet. ii:392–3 (1982).CrossRefGoogle Scholar
  62. 62.
    J. Hartiala, N Simberg, and P. Uotila, Exposure to CO or nicotine does not inhibit PGI2 production by rat arterial rings incubated with human platelet rich plasma, Artery. 10:412–9 (1982).PubMedGoogle Scholar
  63. 63.
    P. Nicod, R. Rehr, M. D. Winniford, W. B. Campbell, B. G. Firth, and L. P. Hillis, Acute systemic and coronary hemodynamic and serologic response to cigarette smoking in chronic smokers with atherosclerotic coronary artery disease, JACC. 4:964–71 (1984).PubMedGoogle Scholar
  64. 64.
    M. L. Bierenbaum, A. I. Fleischman, and A. Stier, Effect of cigarette smoking upon in vivo platelet function in man, Thromb Res. 12:1051–7 (1978).PubMedCrossRefGoogle Scholar
  65. 65.
    H. C. McGill Jr., The cardiovascular pathology of smoking, Am Heart J. 115:250–7 (1988).PubMedCrossRefGoogle Scholar
  66. 66.
    J. W. Davis, C. R. Hartman, H. D. Lewis Jr., L. Shelton, D. A. Eigenberg, K. M. Hassanein, C. E. Hignite, and H. A. Ruttinger, Cigarette smoking-induced enhancement of platelet function: lack of prevention by aspirin in men with coronary artery disease, J Lab Clin Med. 105:479–83 (1985).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • J. D. Folts
    • 1
  • S. A. Gering
    • 1
  • S. W. Laibly
    • 1
  • B. G. Bertha
    • 1
  • F. C. Bonebrake
    • 1
  • J. W. Keller
    • 1
  1. 1.Department of MedicineUniversity of WisconsinMadisonUSA

Personalised recommendations