Clinical Significance of Coronary Vasomotor Tone in Myocardial Ischemia

  • Juan C. Kaski
  • Attilio Maseri


Our understanding of the pathogenic mechanisms underlying chronic stable angina, unstable angina and Prinzmetal’s variant angina has increased in recent years. There is now general agreement that dynamic coronary stenoses may contribute to these ischemic syndromes [15, 24, 25]. Dynamic stenoses can be caused by increase of coronary vasomotor tone, coronary thrombosis or by a combination of the two. The thrombotic component confers to the anginal syndromes the feature of instability and the tendency to evolve towards myocardial infarction [18, 32]. It is now generally accepted that an episodic increase of the vasomotor tone of epicardial coronary arteries is not only the cause of variant angina but may also be a pathogenic component in other more common anginal syndromes [15,18, 24, 25, 32, 50, 77]. Although the terms “coronary spasm” and “coronary vasoconstriction” are frequently used synonymous in medical literature to indicate increases in coronary vasomotor tone, a distinction between the two is necessary, as the difference between coronary spasm, as seen in variant angina, and the coronary vasoconstriction commonly observed in chronic stable angina is not only one of degree, but it seems to reflect also different underlying mechanisms.


Acute Myocardial Infarction Unstable Angina Stable Angina Chronic Stable Angina Epicardial Coronary Artery 
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.


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  1. 1.
    Ambrose J, Winters S, Stern A, Eng A, Teicholz L, Gorlin R, Fuster V (1985) Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 5:609–616PubMedCrossRefGoogle Scholar
  2. 2.
    Bayliss (1902) On the local reaction of the arterial wall to changes in internal pressure. J Physiol (London) 28:220–231Google Scholar
  3. 3.
    Bertrand ME, Lablanche JM, Tilmant PY, Thienleux FA, Delforge MR, Carre AG, Asseman P, Berzin B, Libersa B, Laurent JM (1982) Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation 65:1299–1306PubMedCrossRefGoogle Scholar
  4. 4.
    Bertrand ME, Lablanche JM, Tilmant PY, Thieuleux FA, Delforge MG, Chahine RA (1983) The provocation of coronary arterial spasm in patients with recent transmural myocardial infarction. Eur Heart J 4:532–535PubMedGoogle Scholar
  5. 5.
    Biagini A, Mazzei MG, Carpeggiani C, Testa R, Antonelli R, Michelassi C, L’Abbate A, Maseri A (1982) Vasospastic ischemic mechanism of frequent asymptomatic transient ST-T changes during continuous electrocardiographic monitoring in selected unstable angina patients. Am Heart J 103:13–20PubMedCrossRefGoogle Scholar
  6. 6.
    Brown BG, Bolson E, Petersen RB, Pierce CD, Dodge HT (1981) The mechanisms of nitroglycerin action: stenosis vasodilatation as a major component of the drug response. Circulation 69:1089–1097CrossRefGoogle Scholar
  7. 7.
    Brown BG, Lee AB, Bolson EL, Dodge HT (1984) Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise. Circulation 70:18–24PubMedCrossRefGoogle Scholar
  8. 8.
    Brown BG (1985) Response of normal and diseased epicardial coronary arteries to vasoactive drugs: Quantitative arteriographic studies. Am J Cardiol 56:23E-29EPubMedCrossRefGoogle Scholar
  9. 9.
    Burnstock G (1985) Neurohumoral control of blood vessels: some future directions. J Cardiovasc Pharmacol 7:S137-S146PubMedCrossRefGoogle Scholar
  10. 10.
    Capone G, Wolf NM, Meyer B, Meister SG (1985) Frequency of intracoronary filling defects by angiography in angina pectoris at rest. Am J Cardiol 56:403–406PubMedCrossRefGoogle Scholar
  11. 11.
    Chierchia S, Balasubramanian V, Muiesan L, Sonecha T, Davies A, Maseri A (1984) Transient impairment of coronary flow: a frequent cause of ischemia in chronic stable angina during normal daily life. J Am Coll Cardiol 3:579 (abstract)Google Scholar
  12. 12.
    Chierchia S, Gallino A, Smith G, Deanfield J, Morgan M, Croom M, Maseri A (1984) The role of heart rate in the pathophysiology of chronic stable angina. Lancet II:1353–1357CrossRefGoogle Scholar
  13. 13.
    Clarke J, Davies G, Kerwin R, Hackett D, Larkin S, Dawbarn D, Lee Y, Bloom SR, Yacoub M, Maseri A (1987) Coronary artery infusion of neuropeptide Y in patients with angina pectoris. Lancet I:1057–1059CrossRefGoogle Scholar
  14. 14.
    Constantinides P (1966) Plaque fissures in human coronary thrombosis. J Atherosclerosis Res 6:1–17CrossRefGoogle Scholar
  15. 15.
    Crea F, Davies G, Romeo F, Chierchia S, Bugiardini R, Freedman B, Kaski JC, Maseri A (1984) Myocardial ischemia during ergonovine testing: different susceptibility to coronary vasoconstriction in patients with exertional and variant angina. Circulation 69:690–695PubMedCrossRefGoogle Scholar
  16. 16.
    Crea F, Margonato A, Kaski JC, Rodriguez-Plaza L, Meran DO, Davies G, Chierchia S, Maseri A (1986) Variability of results during repeat exercise stress testing in patients with stable angina pectoris: role of dynamic coronary flow reserve. Am Heart J 112:249–254PubMedCrossRefGoogle Scholar
  17. 17.
    Davies G, Chierchia S, Maseri A (1984) Prevention of myocardial infarction by very early treatment with intracoronary streptokinase. Some clinical observations. N Engl J Med 311:1488–1492PubMedCrossRefGoogle Scholar
  18. 18.
    Davies M, Thomas A (1985) Plaque fissuring — the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 53:363–373PubMedCrossRefGoogle Scholar
  19. 19.
    Davies M, Thomas A (1984) Thrombosis and acute coronary artery lesions in sudden cardiac ischemic death. N Engl J Med 310:1137–1140PubMedCrossRefGoogle Scholar
  20. 20.
    De Zwaan C, Bar FW, Janssen JHA, De Swart HB, Vermeer F, Wellens HJJ (1988) Effects of thrombolytic therapy in unstable angina: clinical and angiographic results. J Am Coll Cardiol 12:301–309PubMedCrossRefGoogle Scholar
  21. 21.
    Deanfield JE, Maseri A, Selwyn AP, Chierchia S, Ribeiro P, Krikler S, Morgan M (1983) Myocardial ischaemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes. Lancet II:753–758CrossRefGoogle Scholar
  22. 22.
    Dhurandhar RW, Watt DL, Silver MD, Trimble AS, Adelmann AG (1972) Prinzmetal’s variant form of angina with arteriographic evidence of coronary arterial spasm. Am J Cardiol 30:902–905PubMedCrossRefGoogle Scholar
  23. 23.
    El-Maraghi NRH, Sealey BJ (1980) Recurrent myocardial infarction in a young man due to coronary arterial spasm demonstrated at autopsy. Circulation 61:199–207PubMedCrossRefGoogle Scholar
  24. 24.
    Epstein SE, Palmeri ST (1984) Mechanisms contributing to precipitation of unstable angina and acute myocardial infarction: implications regarding therapy. Am J Cardiol 54:1245–1252PubMedCrossRefGoogle Scholar
  25. 25.
    Epstein SE, Talbot TL (1981) Dynamic coronary tone in precipitation, exacerbation and relief of angina pectoris. Am J Cardiol 48:797–803PubMedCrossRefGoogle Scholar
  26. 26.
    Falk E (1985) Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death: autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 71:699–708PubMedCrossRefGoogle Scholar
  27. 27.
    Feigl EO (1983) Coronary physiology. Physiol Rev 63:1–205PubMedGoogle Scholar
  28. 28.
    Feldman RL (1987) Coronary thrombosis, coronary spasm and coronary atherosclerosis and speculation on the link between unstable angina and acute myocardial infarction. Am J Cardiol 59:1187–1190PubMedCrossRefGoogle Scholar
  29. 29.
    Fitzgerald DJ, Roy L, Catella F, Fitzgerald GA (1986) Platelet activation in unstable coronary disease. N Engl J Med 315:983–989PubMedCrossRefGoogle Scholar
  30. 30.
    Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376PubMedCrossRefGoogle Scholar
  31. 31.
    Furchgott RF (1983) Role of endothelium in responses of vascular smooth muscle. Circ Res 53:557–573PubMedCrossRefGoogle Scholar
  32. 32.
    Fuster V, Badimon L, Cohen M, Ambrose JA, Badimon JJ, Chesebro J (1988) Insights into the pathogenesis of acute ischemic syndromes. Circulation 77:1213–1220PubMedCrossRefGoogle Scholar
  33. 33.
    Fuster V, Chesebro JH (1986) Mechanisms of unstable angina. N Engl J Med 315:1023–1025PubMedCrossRefGoogle Scholar
  34. 34.
    Gage JE, Hess OM, Murakami T, Ritter M, Grimm J, Krayenbühl HP (1986) Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris: reversibility by nitroglycerin. Circulation 73:865–876PubMedCrossRefGoogle Scholar
  35. 35.
    Ginsburg R, Bristow M, Davis K, Dibiaze A, Billingham M (1984) Quantitative pharmacologic responses of normal and atherosclerotic isolated human epicardial coronary arteries. Circulation 69:430–440PubMedCrossRefGoogle Scholar
  36. 36.
    Hackett D, Davies G, Chierchia S, Maseri A (1987) Intermittent coronary occlusion in acute myocardial infarction. Value of combined thrombolytic and vasodilator therapy. N Engl J Med 317:1055–1059PubMedCrossRefGoogle Scholar
  37. 37.
    Hackett D, Davies G, Maseri A (1988) Pre-existing stenoses in patients with first myocardial infarction are not necessarily severe. Eur Heart J 9:1317–1323PubMedCrossRefGoogle Scholar
  38. 38.
    Hackett D, Larkin S, Chierchia S, Davies G, Kaski JC, Maseri A (1987) Induction of coronary artery spasm by a direct local action of ergonovine. Circulation 75:577–582PubMedCrossRefGoogle Scholar
  39. 39.
    Horio Y, Yasue H, Rokutanda M, Nakamura N, Ogawa H, Takaoka K, Matsuyama K, Kimura T (1986) Effects of intracoronary injection of acetylcholine on coronary arterial diameter. Am J Cardiol 57:984–989PubMedCrossRefGoogle Scholar
  40. 40.
    Johnson PC (1983) The myogenic response. In: Bohr DF, Somlyo AV, Sparks HV Jr (eds) Handbook of Physiology, Circulation 2, Vascular Smooth Muscle, pp 409–439Google Scholar
  41. 41.
    Kaski JC, Crea F, Meran D, Rodriguez L, Araujo L, Chierchia S, Davies G, Maseri A (1986) Local coronary super-sensitivity to diverse vasoconstrictive stimuli in patients with variant angina. Circulation 74:1255–1265PubMedCrossRefGoogle Scholar
  42. 42.
    Kaski JC, Crea F (1987) Practical assessment of the role of dynamic coronary stenoses in patients with stable exertional angina. In: Maseri A, Sobel BE, Chierchia S (eds) Hammersmith Cardiology Workshop Series Vol 3. Raven Press, New York: 117Google Scholar
  43. 43.
    Kaski JC, Rodriguez-Plaza L, Meran DO, Araujo L, Chierchia S, Maseri A (1985) Improved coronary supply: the prevailing mechanism of action of nitrates in chronic stable angina. Am Heart J 110:238–245PubMedCrossRefGoogle Scholar
  44. 44.
    Keefer CS, Resnik WH (1928) Angina pectoris. A syndrome caused by anoxemia of the myocardium. Arch Intern Med 41:769–807CrossRefGoogle Scholar
  45. 45.
    Klassen GA, Wong AYK (1982) Coronary artery compliance in the dog. Can J Physiol Pharmacol 60:942–951PubMedCrossRefGoogle Scholar
  46. 46.
    Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P (1986) Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315:1046–1051PubMedCrossRefGoogle Scholar
  47. 47.
    MacAlpin RN, Kattus AA, Alvaro AB (1973) Angina pectoris at rest with preservation of exercise capacity: Prinzmetal’s variant angina. Circulation 47:946–958PubMedCrossRefGoogle Scholar
  48. 48.
    MacAlpin RN (1980) Contribution of dynamic vascular wall thickening to luminal narrowing during coronary arterial constriction. Circulation 61:296–301PubMedCrossRefGoogle Scholar
  49. 49.
    Maseri A, Chierchia S, Davies G (1986) Pathophysiology of coronary occlusion in acute infarction. Circulation 73:233–239PubMedCrossRefGoogle Scholar
  50. 50.
    Maseri A, Chierchia S, Kaski JC (1985) Mixed angina pectoris. Am J Cardiol 56:30E-33EPubMedCrossRefGoogle Scholar
  51. 51.
    Maseri A, Chierchia S (1982) Coronary artery spasm: demonstration, definition, diagnosis and consequences. Prog Cardiovasc Dis 25:169–192PubMedCrossRefGoogle Scholar
  52. 52.
    Maseri A, L’Abbate A, Baroldi G, Chierchia S, Marzilli M, Ballestra AM, Severi S, Parodi O, Biagini A, Distante A, Pesola A (1978) Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of “preinfarction” angina. N Engl J Med 299:1271–1277PubMedCrossRefGoogle Scholar
  53. 53.
    Maseri A, Mimmo R, Chierchia S, Marchesi C, Pesola A, L’Abbate A (1975) Coronary artery spasm as a cause of acute myocardial ischemia in man. Chest 68:625–633CrossRefGoogle Scholar
  54. 54.
    Maseri A, Parodi O, Severi S, Pesola A (1976) Transient transmural reduction of myocardial blood flow, demonstrated by thallium-201 scintigraphy, a cause of variant angina. Circulation 54:280–288PubMedCrossRefGoogle Scholar
  55. 55.
    Maseri A, L’Abbate A, Pesola A, Ballestra AM, Marzilli M, Maltini G, Severi S, De Nes DM, Parodi O, Biagini A (1977) Coronary vasospasm in angina pectoris. Lancet I:713–717CrossRefGoogle Scholar
  56. 56.
    Maseri A, Seven S, De Nes M, L’Abbate A, Chierchia S, Marzilli M, Ballestra AM, Parodi O, Biagini A, Distante A (1978) “Variant” angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 42:1019–1035PubMedCrossRefGoogle Scholar
  57. 57.
    Maseri A, Seven S, Marzullo P (1982) Role of coronary arterial spasm in sudden coronary ischemic death. Ann N Y Acad Sci 204–217Google Scholar
  58. 58.
    Maseri A (1980) Pathogenetic mechanisms of angina pectoris: expanding views. Br Heart J 43:648–660PubMedCrossRefGoogle Scholar
  59. 59.
    Maseri A (1984) Spasm and dynamic coronary stenosis. J Cardiovasc Pharmacol 6:S683-S690PubMedCrossRefGoogle Scholar
  60. 60.
    Meller J, Pickard A, Dack S (1976) Coronary arterial spasm in Prinzmetal’s angina: a proved hypothesis. Am J Cardiol 37:938–940PubMedCrossRefGoogle Scholar
  61. 61.
    Nakamura M, Takeshita A, Nose Y (1987) Clinical characteristics associated with myocardial infarction, arrhythmias, and sudden death in patients with vasospastic angina. Circulation 75:1110–1116PubMedCrossRefGoogle Scholar
  62. 62.
    Oliva PB, Breckinridge JC (1977) Arteriographic evidence of coronary arterial spasm in acute myocardial infarction. Circulation 56:366–374PubMedCrossRefGoogle Scholar
  63. 63.
    Oliva PB, Potts DE, Pluss RG (1973) Coronary arterial spasm in Prinzmetal angina. Documentation by coronary arteriography. N Engl J Med 288:745–751PubMedCrossRefGoogle Scholar
  64. 64.
    Osler W (1910) The Lumlean lectures on angina pectoris II. Lancet I:839–844CrossRefGoogle Scholar
  65. 65.
    Pickering GW (1951) Vascular spasm. Lancet II:845–850CrossRefGoogle Scholar
  66. 66.
    Prinzmetal M, Kennamer R, Merliss R (1959) Angina pectoris. A variant form of angina pectoris. Am J Med 27:375–388PubMedCrossRefGoogle Scholar
  67. 67.
    Roberts WC, Curry RC Jr, Isner JM, Waller BF, McManus BM, Mariani-Constantini R, Ross AM (1982) Sudden death in Prinzmetal’s angina with coronary spasm documented by angiography. Am J Cardiol 50:203–210PubMedCrossRefGoogle Scholar
  68. 68.
    Seven S, Davies G, Maseri A, Marzullo P, L’Abbate A (1980) Long-term prognosis of “variant” angina with medical treatment. Am J Cardiol 46:226–232CrossRefGoogle Scholar
  69. 69.
    Sheehan FH, Epstein SE (1982) Determinants of arrhythmic death due to coronary spasm: effect of preexisting coronary artery stenosis on the incidende of reperfusion arrhythmia. Circulation 65:259–264PubMedCrossRefGoogle Scholar
  70. 70.
    Sherman CT, Litvack F, Grundfest W, Lee M, Hickey A, Chaux A, Kass R, Blanche C, Matloff J, Morgenstern L, Ganz W, Swan HJC, Forrester J (1986) Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med 315:913–919PubMedCrossRefGoogle Scholar
  71. 71.
    Shubrooks SJ (1979) Variant angina: more variants of the variant. Am J Cardiol 43:1245–1247PubMedCrossRefGoogle Scholar
  72. 72.
    Specchia G, De Servi S, Falcone C, Bramucci E, Angoli L, Mussini A, Marinoni GP, Montemartini C, Bobba P (1979) Coronary arterial spasm as a cause of exercise-induced ST-segment elevation in patients with variant angina. Circulation 59:948–954PubMedCrossRefGoogle Scholar
  73. 73.
    Theroux P, Ouimet H, McCans J, Latour JG, Joly P, Levy G, Pelletier E, Juneau M, Stasiak J, DeGuise P, Pelletier GB, Rinzler D, Waters DD (1988) Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 319:1105–1111PubMedCrossRefGoogle Scholar
  74. 74.
    Vincent MG, Anderson JL, Marshall HW (1983) Coronary spasm producing coronary thrombosis and myocardial infarction. N Engl J Med 309:220–223PubMedCrossRefGoogle Scholar
  75. 75.
    Vlodaver Z, Edward JE (1971) Pathology of coronary atherosclerosis. Prog Cardiovasc Dis 14:256–259PubMedCrossRefGoogle Scholar
  76. 76.
    Waters DD, Szlachcic J, Bonan R, Miller DD, Davue R, Theroux P (1983) Comparative sensitivity of exercise, cold pressor and ergonovine testing in provoking attacks of variant angina in patients with active disease. Circulation 67:310–315PubMedCrossRefGoogle Scholar
  77. 77.
    Willerson JT, Hillis LD, Winniford M, Buja LM (1986) Speculation regarding mechanisms responsible for acute ischemic heart disease syndromes. J Am Coll Cardiol 8:245–250PubMedCrossRefGoogle Scholar
  78. 78.
    Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415PubMedCrossRefGoogle Scholar
  79. 79.
    Yasue H, Horio Y, Nakamura N, Fujii H, Imoto N, Sonoda R, Kugiyama K, Obata K, Morikami Y, Kimura T (1986) Induction of coronary artery spasm by acetylcholine in patients with variant angina: possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm. Circulation 74:955–963PubMedCrossRefGoogle Scholar
  80. 80.
    Yasue H, Omote S, Takizawa A, Nagao M, Miwa K, Tanaka S (1979) Circadian variation of exercise capacity in patients with Prinzmetal’s variant angina: Role of exercise-induced coronary arterial spasm. Circulation 59:938–948PubMedCrossRefGoogle Scholar
  81. 81.
    Yasue H, Omote S, Takizawa A, Masao N, Hyon H, Nishida S, Horie M (1981) Comparison of coronary arteriographic findings during angina pectoris associated with S-T elevation or depression. Am J Cardiol 47:539–546PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • Juan C. Kaski
    • 1
  • Attilio Maseri
    • 1
  1. 1.The Cardiovascular Research Unit, Royal Postgraduate Medical SchoolHammersmith HospitalLondonEngland

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