European Journal of Nuclear Medicine

, Volume 23, Issue 11, pp 1442–1447 | Cite as

Long-term cigarette smoking is associated with increased myocardial perfusion heterogeneity assessed by positron emission tomography

  • Joan G. Meeder
  • Paul K. Blanksma
  • Ernst E. van der Wall
  • Rutger L. Anthonio
  • Antoon T. M. Willemsen
  • Jan Pruim
  • Wim Vaalburg
  • Kong I. Lie
Original Article


The pathophysiology of smoking-related coronary events in patients with normal coronary arteries is incompletely understood. This study was conducted to explore, in subjects without symptoms of cardiovascular disease, the long-term effects of smoking on regional coronary artery vasoactivity, especially during sympathetic stimulation. In ten smoking and ten non-smoking sex- and age-matched healthy volunteers, segmental myocardial perfusion was studied using dynamic parametric nitrogen-13 ammonia positron emission tomography at rest and during sympathetic stimulation evoked by the cold pressor stimulation. Smokers demonstrated a higher myocardial perfusion at rest (116±17 ml/min/100 g vs 96±20 ml/min/100 g,P <0.01) and an impaired myocardial perfusion increase during cold pressor stimulation (1.02±0.15 vs 1.18±0.17,P <0.05). The heterogeneity of perfusion, expressed as coefficient of variation, was significantly different between the smoking and the non-smoking group. The coefficient of variation of segmental myocardial perfusion was higher in smokers at rest (17.5%±4.2% vs 13.5%±1.9%,P <0.05) and during cold pressor stimulation (17.0%±3.2% vs 13.9%±1.8%,P <0.05). We conclude that the long-term effects of smoking in healthy volunteers are associated with (1) increased myocardial perfusion at rest, (2) impaired myocardial perfusion response to cold pressor stimulation, and (3) increased myocardial perfusion heterogeneity both at rest and during cold pressor stimulation. These results may suggest that in healthy subjects the longterm effect of smoking is related to abnormal coronary artery vasoactivity, presumably induced by an interplay of regional endothelial dysfunction and autonomic dysregulation.

Key words

Smoking Positron emission tomography Myocardial perfusion heterogeneity Cold pressor stimulation Endothelial function 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Holbrook S, Grundy SM, Hennekens CH, Kannel WB, Strong JP. Cigarette smoking and cardiovascular disease: a statement for health professionals by a task force appointed by the steering committee of the American Heart Association.Circulation 1984; 70: 1114–1117.Google Scholar
  2. 2.
    Hayano J, Yamada M, Sakakibara Y, et al. Short- and longterm effects of cigarette smoking on heart rate variability.Am J Cardiol 1990; 65: 84–88.PubMedGoogle Scholar
  3. 3.
    Molgaard H, Sorensen KE, Bjerregaard P. Circadian variation and influence of risk factors on heart rate variability in healthy subjects.Am J Cardiol 1991; 68: 777–784.PubMedGoogle Scholar
  4. 4.
    Levin FR, Levin HR, Nagoshi C. Autonomic functioning and cigarette smoking: heart rate spectral analysis.Biol Psychiatry 1992; 31: 639–643.PubMedGoogle Scholar
  5. 5.
    Zimmerman M, McGeachie J. The effect for nicotine on aortic endothelial cell turnover. An autoradiographic study.Atherosclerosis 1985; 58: 39–47.PubMedGoogle Scholar
  6. 6.
    Pittilo RM, Bull HA, Gulati S, et al. Nicotine and cigarette smoking: effects on the ultrastructure of aortic endothelium.Int J Exp Pathol 1990; 71: 573–586.PubMedGoogle Scholar
  7. 7.
    Nitenberger A, Antony I, Foult JM. Acetylcholine-induced coronary vasoconstriction in young, heavy smokers with normal coronary arteriographic findings.Am J Med 1993; 95: 71–77.PubMedGoogle Scholar
  8. 8.
    Sugiishi M, Takatsu F. Cigarette smoking is a major risk factor for coronary spasm.Circulation 1993; 87: 76–79.PubMedGoogle Scholar
  9. 9.
    McKenna WJ, Chew CY, Oakley CM. Myocardial infarction with normal coronary angiogram: possible mechanism of smoking risk in coronary artery disease.Br Heart J 1980; 43: 493–498.PubMedGoogle Scholar
  10. 10.
    Kannel WB, Schatzkin A. Sudden death: lessons from subsets in population studies.J Am Coll Cardiol 1985; 5: 141–149.Google Scholar
  11. 11.
    Meeder JG, Blanksma PK, Anthonio RL, Willemsen ATM, Pruim J. Positron emission tomography and detection of endothelial dysfunction. In: Gilst van WH, Lie KI, eds.Neurohumoral regulation of coronary flow. Dordrecht: Kluwer Academic; 1993: 73–88.Google Scholar
  12. 12.
    Blanksma PK, Willemsen ATM, Meeder JG, et al. Quantitative myocardial mapping of perfusion and metabolism using parametric polar map displays in cardiac PET.J Nucl Med 1995; 35: 153–158.Google Scholar
  13. 13.
    Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium.J Am Coll Cardiol 1989; 14: 1181–1190.PubMedGoogle Scholar
  14. 14.
    Zeiher AM, Drexler H, Wollschläger H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with impaired coronary blood flow regulation in patients with early atherosclerosis.Circulation 1991; 84: 1984–1992.PubMedGoogle Scholar
  15. 15.
    Meeder JG, Peels HOH, Blanksma PK, Tan ES, Pruim J, Vaalburg W, Lie KI. Assessment of coronary endothelial function in man: comparison between positron emission tomographic perfusion imaging and intracoronary Doppler flow velocity technique [abstract].Eur Heart J 1995; 16: 566.Google Scholar
  16. 16.
    Smits P, Thien T, van't Laar A. Circulatory effects of coffee in relation to the pharmacokinetics of caffeine.Am J Cardiol 1985; 56: 958–963.PubMedGoogle Scholar
  17. 17.
    Benowitz N. Drug therapy: pharmacologic aspects of cigarette smoking and nicotine addiction.N Engl J Med 1988; 319: 1318–1330.PubMedGoogle Scholar
  18. 18.
    Cryer PE, Haymond MW, Santiago JV, Shah SD. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated changes in hemodynamic and metabolic events.N Engl J Med 1976; 295: 573–577.PubMedGoogle Scholar
  19. 19.
    Schelbert HR, Phelps ME, Huang SC, McDonald NS, Hansen H, Selin C, Kuhl DE. N-13 ammonia as an indicator of myocardial blood flow.Circulation 1981; 63: 1259–1272.PubMedGoogle Scholar
  20. 20.
    Bellina CR, Parodi O, Camici P, et al. Simultaneous in vitro and in vivo validation of nitrogen-13-ammonia for the assessment of regional myocardial blood flow.J Nucl Med 1990; 31: 1335–1343.PubMedGoogle Scholar
  21. 21.
    Antony I, Aptecar E, Lerebours G, Nitenberg A. Coronary artery constriction caused by the cold pressor test in human hypertension.Hypertension 1994; 24: 212–259.PubMedGoogle Scholar
  22. 22.
    Robertson D, Johnson GA, Robertson RM, Nies AS, Shand DG, Oates JA. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man.Circulation 1979; 59: 637–642.PubMedGoogle Scholar
  23. 23.
    Geltman EM, Henes G, Senneff MJ, Sobel BE, Bergmann SR. Increased myocardial perfusion at rest and diminished perfusion reserve in patients with angina and angiographically normal coronary arteries.J Am Coll Cardiol 1990; 16: 586–589.PubMedGoogle Scholar
  24. 24.
    Galassi AR, Crea F, Araujo LI, et al. Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease.Am J Cardiol 1993; 72: 134–139.PubMedGoogle Scholar
  25. 25.
    Meeder JG, Blanksma PK, Crijns HJGM, et al. Mechanisms of angina pectoris in syndrome X assessed by myocardial perfusion dynamics and heart rate variability.Eur Heart J 1995; 16: 1571–1577.PubMedGoogle Scholar
  26. 26.
    Ludmer PL, Selwyn AP, Shook THL, Wayne RR, Mudge GH, Alexander RY, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.N Engl J Med 1986; 315: 1046–1051.PubMedGoogle Scholar
  27. 27.
    Werns SW, Walton JA, Hsia HH, Nabel EG, Ganz ML, Pitt B. Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease.Circulation 1989; 79: 287–291.PubMedGoogle Scholar
  28. 28.
    Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P. Coronary vasomotive response to acetylcholine relates to risk factors for coronary artery disease.Circulation 1990; 81: 491–497.PubMedGoogle Scholar
  29. 29.
    Vane JR, Änggard EE, Botting RM. Regulatory functions of the vascular endothelium.N Engl J Med 1990; 323: 27–36.PubMedGoogle Scholar
  30. 30.
    Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans.Circulation 1989; 79: 93–100.PubMedGoogle Scholar
  31. 31.
    Vogel RA. Endothelium-dependent vasoregulation of coronary artery diameter and blood flow.Circulation 1993; 88: 325–327.PubMedGoogle Scholar
  32. 32.
    Zeiher AM, Schächinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function.Circulation 1995; 92: 1094–1100.PubMedGoogle Scholar
  33. 33.
    Celermajer DS, Sorensen KE, Georgakopoulos D, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults.Circulation 1993, 88: 2149–2155.PubMedGoogle Scholar
  34. 34.
    Kiowski W, Linder L, Stoschitzky K, et al. Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers.Circulation 1994; 90: 27–34.PubMedGoogle Scholar
  35. 35.
    De Sousa P, Cherian G, Thomas J, Thulesius O. Coronary artery constriction is enhanced with nicotine and propranolol, particularly after endothelial damage.Clin Physiol 1991; 11: 143–153.PubMedGoogle Scholar
  36. 36.
    Deanfield JE, Shea MJ, Wilson RA, Horlock P, de Landsheere CM, Selwyn AP. Direct effects of smoking on the heart: silent ischemic disturbances of coronary flow.Am J Cardiol 1986; 57: 1005–1009.PubMedGoogle Scholar
  37. 37.
    Moliterno DJ, Willard JE, Lange RA. Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both.N Engl J Med 1994; 330: 454–459.PubMedGoogle Scholar
  38. 38.
    Czernin J, Sun K, Brunken R, Böttcher M, Phelps M, Schelbert H. Effect of acute and long-term smoking on myocardial blood flow and flow reserve.Circulation 1995; 91: 2891–2897.PubMedGoogle Scholar
  39. 39.
    Groppelli A, Omboni S, Parati G, Mancia G. Blood pressure and heart rate response to repeated smoking before and after beta-blockade and selective alpha 1 inhibition.J Hypertens 1990; 8 Suppl 5: S35-S40.Google Scholar
  40. 40.
    Goldbourt U, Medalie JH. Characteristics of smokers, nonsmokers and ex-smokers among 10000 adult males in Israel. II. Physiologic, biochemical and genetic characteristics.Am J Epidemiol 1977; 105: 78–86.Google Scholar
  41. 41.
    Green MS, Jucha E, Luz Y. Blood pressure in smokers and nonsmokers: epidemiologic findings.Am Heart J 1986; 111: 932–940.PubMedGoogle Scholar
  42. 42.
    Klein LW. Cigarette smoking, atherosclerosis and the coronary hemodynamic response: a unifying hypothesis.J Am Coll Cardiol 1984; 4: 972–974.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Joan G. Meeder
    • 1
  • Paul K. Blanksma
    • 1
  • Ernst E. van der Wall
    • 2
  • Rutger L. Anthonio
    • 1
  • Antoon T. M. Willemsen
    • 1
  • Jan Pruim
    • 1
  • Wim Vaalburg
    • 1
  • Kong I. Lie
    • 1
  1. 1.Department of Cardiology and National Research PET CenterUniversity Hospital GroningenThe Netherlands
  2. 2.Department of CardiologyLeiden University HospitalLeidenThe Netherlands

Personalised recommendations