Advertisement

Pathophysiology of Ischemic Heart Disease with Special Reference to Coronary Artery Spasm

  • M. Nakamura

Summary

Traditionally, ischemic heart disease has been considered the sequence of fixed atherosclerotic obstruction of the large epicardial coronary arteries. However, clinical hemodynamic, angiographic, scintigraphic and metabolic and animal studies have provided independent evidence for an increase in vasomotor tone, especially coronary spasm, as an important cause of various stages of ischemic heart disease. Factors that initiate or sustain the syndrome related to coronary spasm have not been completely defined, and a porcine model of coronary spasm was prepared in our laboratory.

The hypothesis of coronary spasm as a cause of angina pectoris was proposed during the 19th century. In the 1920’s, the close association between angina and atherosclerotic coronary narrowing was confirmed by pathological studies and coronary angiographic support was obtained in 1960s and 1970s, which neglected the presence of coronary spasm.

Beginning in the 1930s, there were reports of spontaneous angina not associated with increased myocardial oxygen demand. In 1959, Prinzmetal et al. summarized these cases, and reported a variant form of angina pectoris, ignoring the myocardial oxygen demand-supply imbalance theory. They proposed that increased coronary artery tonus was the cause of this variant angina. During the 1970s, Maseri and other investigators clearly demonstrated that coronary spasm is a major cause of variant angina.

Coronary spasm is now accepted as a major cause of variant angina, a significant proportion of rest angina and rest and effort angina, some cases of effort angina and postmyocardial infarctional angina, and possibly acute ischemia related death including acute myocardial infarction. However the link between coronary spasm, progression of organic stenosis, and thrombotic occlusion of coronary arteries is missing.

The pathophysiology of acute myocardial infraction is also uncertain. Recent clinical and pathophysiological studies have indicated that coronary-occlusive thrombi occur frequently in the early stage of transmural infarct, but infrequently with subendocardial infarct and sudden ischemic death. Mechanisms and factors which initiate coronary thrombosis are unknown. Falk deduced from pathological studies that rupture of the atheromatous plaque surface was always accompanied by hemorrhage into the plaque, but occlusive thorombosis was rare unless the rupture was associated with a stenosis greater than 75%. Thrombi in arteries are frequently located on the surface of atherosclerotic plaques, and not necessarily in the arteries related to myocardial infarction.

The antithesis to thrombosis as a cause of acute myocardial infarction is intramural hemorrhage in the atheroma as the primary event causing coronary occlusion. Clinical evidence supporting coronary spasm as the pathogenesis of acute myocardial infarct has been reported. The recent hypothesis that acute myocardial infarction occurs as a direct result of coronary spasm has not been fully proven. Thus, various studies on the development of suitable animal models of coronary spasm have been performed.

An animal model of coronary spasm should be helpful in clarifying mechanisms and roles of spasm in various stages of ischemic heart disease, including progression of organic stenosis and possibly acute coronary occlusion.

Gensini et al. were the first to demonstrate diffuse coronary spasm by giving pitressin to a normal dog, in 1962. In 1983, we developed a porcine model of coronary spasm in mildly atherosclerotic miniature swine, by injecting histamine and serotonin. We have recently improved the animal model of coronary spasm in moderate coronary atherosclerosis by giving serotonin, ergonovine, and hyperventilation, similar to what occurs in patients with variant angina.

In isolated coronary artery segments from atherosclerotic miniature swine, we found that a decrease in endothelium-dependent relaxing function and abnormal hypercontraction of the media of atherosclerotic coronary arteries. These events may result from an increased number of receptors for agonists, and/or augumentation of signal transduction, but not by increased calcium sensitivity of contractile proteins in the medial smooth muscle cells.

I will discuss about the following; a) the role of preexisting coronary atherosclerosis, b) neural factors, such as the adrenergic and parasympathetic nervous systems, c) autacoids, such as histamine and serotonin in the development of coronary spasm, and d) variations in in vitro, in vivo, and inter-species evidence.

Keywords

Coronary Artery Acute Myocardial Infarction Ischemic Heart Disease Angina Pectoris Human 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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    MacAlpine RN (1980) Coronary arterial spasm; A historical perspective. J Hist Med Allied Sci 35: 288–311Google Scholar
  2. 2.
    Osier W (1910) The Lumleian lectures on angina pectoris II. Lancet I: 839–844Google Scholar
  3. 3.
    Keefer CS, Resnik WH (1928) Angina pectoris: A syndrome caused by anoxemia of the myocardium. Arch Intern Med 41: 769–807Google Scholar
  4. 4.
    Blumgart HL, Schlesinger MJ, Davis D (1940) Studies on the relation of the clinical manifestations of angina pectoris, coronary thrombosis and myocardial infarction to the pathologic findings. Am Heart J 19: 1–91Google Scholar
  5. 5.
    Zoll PM, Wessler S, Blumgart HL (1951) Angina pectoris; a clinical and pathological correlation. Am J Med 11: 331–357PubMedGoogle Scholar
  6. 6.
    Proudfit WL, Shirey EK, Sones FM (1966) Selective cine coronary arteriography; Correlation with clinical findings in 1,000 patients. Circulation 33: 901–910PubMedGoogle Scholar
  7. 7.
    Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N (1959) Angina pectoris I: A variant form of angina pectoris preliminary report. Am J Med 27: 375–388PubMedGoogle Scholar
  8. 8.
    Guazzi M, Polese A, Fiorentini C, Magrini F, Bartorelli C (1971) Left ventricular performance and related hemodynamic changes in Prinzmetal’s variant angina pectoris. Br Heart J 33: 84–94PubMedGoogle Scholar
  9. 9.
    Scherf D, Cohen J (1974) Variant ’’ angina pectoris. Circulation 49: 787–789PubMedGoogle Scholar
  10. 10.
    Epstein SE, Redwood DR, Goldstein RE, Beiser GD, Rosing DR, Glancy DL, Reis RL, Stinson EB (1971) Angina pectoris: pathophysiology, evaluation and treatment. Ann Intern Med 75: 263–296Google Scholar
  11. 11.
    Maseri A, Minno 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: 625–632Google Scholar
  12. 12.
    Maseri A, Severi S, DeNes M, L’Abbate A, Chierchia S, Marzilli M, Ballestra AM, Parodi O, Biagini A, Distante A (1978) “Variant” angina: One aspect of continuous spectrum of vasospastic myocardial ischemia. Pathogenetic mechanisms, estimated incidence, clinical and coronarographic findings in 138 patients. Am J Cardiol 42: 1019–1035PubMedGoogle Scholar
  13. 13.
    Maseri A, Chierchia S (1982) Coronary artery spasm: Demonstration, definition, diagnosis, and consequences. Prog Cardiovasc Dis. 25: 169–192PubMedGoogle Scholar
  14. 14.
    Shimokawa H, Nagasawa K, Irie T, Egashira S, Egashira K, Sagara T, Kikuchi Y, Nakamura M (1988) Clinical characteristics and long term prognosis of patients with variant angina. A comparative study between western and Japanese populations. Int J Cardiol 18: 331–349Google Scholar
  15. 15.
    Nakamura M (1987) Task report: Basic and clinical studies of coronary spasm (in Japanese). J Jap. Soc Intern Med 76: 1171–1187Google Scholar
  16. 16.
    Hiramori K (1985) Clinical problems related to vasospastic angina (in Japanese). J Jap. Coll Angiol 25: 399–403Google Scholar
  17. 17.
    Nakamura M, Takeshita A, Nose Y (1987) Clinical characteristics associated with myocardial infarction, arrhythmias and sudden death in patients with vasospastic angina. Circulation 75: 1160–1116Google Scholar
  18. 18.
    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: 948–954PubMedGoogle Scholar
  19. 19.
    Yasue H, Omote S, Takizawa A, Nagao M, Miwa K, Tanaka S (1979) Exertional angina pectoris caused by coronary arteria spasm; effects of various drugs. Am J Cardiol 43: 647–652PubMedGoogle Scholar
  20. 20.
    Bertrand ME, Lablanche JM, Tilmant PY (1980) Frequency of provocated coronary artery spasm in 273 patients with chest pain (abstract). Am J Cardiol 45: 390Google Scholar
  21. 21.
    Koiwaya Y, Torii S, Takeshita A, Nakagaki O, Nakamura M (1982) Postinfarction angina caused by coronary arterial spasm. Circulation 65: 275–280PubMedGoogle Scholar
  22. 22.
    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: 1271–1277PubMedGoogle Scholar
  23. 23.
    Oliva PB, Breckinridge JC (1977) Arteriographic evidence of coronary arterial spasm in acute myocardial infarction. Circulation 56: 336–374Google Scholar
  24. 24.
    Marzilli M, Goldstein S, Trirella MG, Palumbo C, Maseri A (1980) Some clinical considerations regarding the relation of coronary vasospasm to coronary atherosclerosis; A hypothetical pathogenesis. Am J Cardiol 45: 882–886PubMedGoogle Scholar
  25. 25.
    Lown B, Desilva RA (1980) Is coronary arterial spasm a risk factor for coronary atherosclerosis? (editorials), Am J Cardiol 45: 901–903PubMedGoogle Scholar
  26. 26.
    Shimokawa H, Tomoike H, Nabeyama S, Yamamoto H, Araki H, Nakamura M, Ishii Y, Tanaka K (1983) Coronary artery spasm induced in atherosclerotic miniature swine. Science 221: 560–562PubMedGoogle Scholar
  27. 27.
    Nagasawa K, Tomoike H, Hayashi Y, Yamada A, Yamamoto T, Nakamura M (1989) Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in X-ray irradiated hypercholesterolemic pigs. Circ Res 65: 272–282PubMedGoogle Scholar
  28. 28.
    Dewood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT (1980) Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 303: 897–902PubMedGoogle Scholar
  29. 29.
    Benacerraf A, Scholl JM, Achard F, Tonnelier M, Lavergne G (1983) Coronary spasm and thrombosis associated myocardial infarction in a patient with nearly normal coronary arteries. Circulation 67: 1147–1150PubMedGoogle Scholar
  30. 30.
    Vincent GM, Anderson JL, Marshall HW (1983) Coronary spasm producting coronary thrombosis and myocardial infarction. N Engl J Med 309: 220–223PubMedGoogle Scholar
  31. 31.
    Conti RC, Feldman RL (1985) Acute myocardial infarction: Thoughts about pathogenesis and treatment. Mod Con Cardiovasc Dis 54: 35–38Google Scholar
  32. 32.
    Spann JF (1983) Changing concepts of pathophysiology, prognosis and therapy in acute myocardial infarction. Am J Med 74: 877–886PubMedGoogle Scholar
  33. 33.
    Rentrop P, Blanke H, Karsch KR, Kaiser H, Kostering H, Leitz K (1981) Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 63: 307–317PubMedGoogle Scholar
  34. 34.
    Leinbach RC, Gold HK (1982) Coronary angiography during acute myocardial infarction: A search for spasm. Am Heart J 103: 768–772PubMedGoogle Scholar
  35. 35.
    Scotti TM, Hackel DB (1985) Heart. In: Kissane J (ed) Anderson’s pathology, 8th edn. Mosby, St. Louis, pp 560–662Google Scholar
  36. 36.
    Hatanaka K, Ito T, Shiomi M, Yamamoto A, Watanabe Y (1987) Ischemic heart disease in the WHHL rabbit; A model for myocardial injury in genetically hyperlipidemic animals. Am Heart J 113: 280–288PubMedGoogle Scholar
  37. 37.
    Falk E (1983) Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis; Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 50: 127–134PubMedGoogle Scholar
  38. 38.
    Constantinides P (1984) Atherosclerosis-A general survey and synthesis. Surv Syn Path Res 3: 477–498Google Scholar
  39. 39.
    Wartman WB (1938) Occlusion of the coronary arteries by hemorrhage into their walls. Am Heart J 15: 459–470Google Scholar
  40. 40.
    Paterson JC (1938) Capillary rupture with intimal hemorrhage as a causative factor in coronary thrombosis. Arch Pathol 25: 474–487Google Scholar
  41. 41.
    Singh RN (1984) Progression of coronary atherosclerosis; Clues to pathogenesis from serial coronary arteriography. Br Heart J 52: 451–461PubMedGoogle Scholar
  42. 42.
    Davies MJ, Thomas AC (1985) Plaque fissuring-the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J 53: 363–373PubMedGoogle Scholar
  43. 43.
    Conti RC (1985) Variant angina and coronary artery spasm. In: Connor WE, Bristow ID (eds) coronary heart disease. Lippincott, Philadelphia, pp 251–267Google Scholar
  44. 44.
    Maseri A, L’Abbate A, Chierchia S, Parodi O, Severi S, Biagini A, Distante A, Marzilli M, Ballestra AM (1979) Significance of spasm in the pathogenesis of ischemic heart disease. Am J Cardiol 44: 788–792PubMedGoogle Scholar
  45. 45.
    Oliva PB, Ridge W (1984) Unstable rest angina with ST-segment depression. Ann Intern Med 100: 424–440PubMedGoogle Scholar
  46. 46.
    Brown BG, Dodge HT (1982) Unstable angina; Guidelines for therapy based on the last decade of clinical observations. Ann Intern Med 97: 921–923PubMedGoogle Scholar
  47. 47.
    Epstein SE, Palmeri ST (1984) Mechanisms contributing to precipitation of unstable angina and acute myocardial infarction; implications regarding therapy. Am J Cardiol 54: 1245–1252PubMedGoogle Scholar
  48. 48.
    Buxon A, Goldberg S (1980) Refractory ergonovine induced coronary vasospasm; importance of intracoronary nitroglycerlin. Am J Cardiol 46: 329–334Google Scholar
  49. 49.
    Crevey BJ, Owen SF, Pitt B (1981) Irreversible coronary occlusion related to administration of ergonovine. Circulation 64: 853–856Google Scholar
  50. 50.
    Bertrand ME, Lablanche JM, Tilmant PY, Thieuleux FA, Delforge MR, Carre AG, Asseman P, Berzin B, Libersa C, Laurrent JM (1982) Frequency of provoked coronary artery spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation 65: 1229–1306Google Scholar
  51. 51.
    Lange R, Reid M, Tresch D, Keelan M, Bernhard V, Coolidge G (1972) Nonatheromatous ischemic heart disease following withdrawal from chronic industrial nitroglycerin exposure. Circulation 46: 666–678PubMedGoogle Scholar
  52. 52.
    MacAlpine RN (1980) Contribution of dynamic vascular wall thickening to luminal narrowing during coronary arterial constriction. Circulation 61: 296–301Google Scholar
  53. 53.
    Cipriano PR, Guthaner DF, Orlick AE, Ricci DR, Wexler L, Silverman JF (1979) The effects of ergonovine maleate on coronary arterial size. Circulation 59: 82–89PubMedGoogle Scholar
  54. 54.
    Tomoike H, Egashira K, Yamada A, Hayashi Y, Nakamura M (1987) Leukotriene C4-and D4-induced diffuse peripheral constriction of swine coronary artery accompanied by ST elevation on the electrocardiogram; angiographic analysis. Circulation 76: 480–487PubMedGoogle Scholar
  55. 55.
    Muramatsu K, Tomoike H, Ohara Y, Egashira S, Nakamura M (to be published) Effects of endothelin on epicardial coronary diameter, coronary blood flow, ECGST changes and wall motion. Heart and VesselsGoogle Scholar
  56. 56.
    Gensini GG, di Giorgi S, Murad-Netto S, Black A (1962) Arteriographic demonstration of coronary artery spasm and its release after the use of a vasodilator in a case of angina pectoris and in the experimental animal. Angiology 13: 550–553PubMedGoogle Scholar
  57. 57.
    Perez JE, Saffitz JE, Gutierrez FA, Henry PD (1983) Coronary artery spasm in intact dogs induced by potassium and serotonin. Circ Res 52: 423–431PubMedGoogle Scholar
  58. 58.
    Shimokawa H, Tomoike H, Nabeyama S, Yamamoto H, Ishii Y, Tanaka K, Nakamura M (1985) Coronary artery spasm induced in miniature swine; angiographic evidence and relation to coronary atherosclerosis. Am Heart J 110: 300–310PubMedGoogle Scholar
  59. 59.
    Yui Y, Sakaguchi K, Susawa T, Hattori R, Takatsu Y, Yui N, Kawai C (1987) Thromboxane A2 analogue induced coronary artery vasoconstriction in the rabbit. Cardiovasc Res 21: 119–123PubMedGoogle Scholar
  60. 60.
    Iwaki M, Mizobuchi S, Nakaya Y, Kawano K, Niki T, Mori H (1987) Tetraethylammonium induced coronary spasm in isolated perfused rabbit heart: A hypothesis for the mechanism of coronary spasm. Cardiov Res. 21: 130–139Google Scholar
  61. 61.
    Yasue H, Touyama M, Kato H, Tanaka S, Akiyama F (1976) Prinzmetal’s variant form of angina as a manifestation of alpha-adrenergic receptor-mediated coronary artery spasm: documentation by coronary arteriography. Am Heart J 91: 148–155PubMedGoogle Scholar
  62. 62.
    Ricci DR, Orlick AE, Cipriano PR, Guthaner DF, Harrision DC (1979) Altered adrenergic activity in coronary arterial spasm; insight into mechanism based on study of coronary hemodynamics and the electrocardiogram. Am J Cardiol 43: 1073–1079PubMedGoogle Scholar
  63. 63.
    Nakamura M, Tomoike H, Ootsubo H, Sakai H, Noguchi K, Takeshita A, Kikuchi Y (1981) Constriction of the epicardial coronary artery induced by alpha-adrenergic stimulation. Basic Res Cardiol 76: 498–502PubMedGoogle Scholar
  64. 64.
    Kawachi Y, Tomoike H, Maruoka Y, Kikuchi Y, Araki H, Ishii Y, Tanaka K, Nakamura M (1984) Selective hypercontraction caused by ergonovine in the canine coronary artery under conditions of induced atherosclerosis. Circulation 69: 441–450PubMedGoogle Scholar
  65. 65.
    Shimokawa H, Tomoike H, Nabeyama S, Yamamoto H, Nakamura M (1985) Histamine-induced spasm not significantly modulated by prostanoids in a swine model of coronary artery spasm. J Am Coll Cardiol 6: 321–327PubMedGoogle Scholar
  66. 66.
    Egashira K, Tomoike H, Yamamoto Y, Yamada A, Hayashi Y, Nakamura M (1986) Histamine-induced coronary spasm in regions of intimal thickening in miniature pigs: roles of serum cholesterol and spontaneous or induced intimal thickening. Circulation 74: 826–837PubMedGoogle Scholar
  67. 67.
    Tomoike H, Hayashi Y, Egashira K, Yamada A, Nakamura M (1989) Effects of atherogenic diets on serum content of cholesterol, histamine-induced coronary constriction and morphological changes of the coronary artery (abstract). Jpn Circ J 53: 900Google Scholar
  68. 68.
    Kuga T, Tagawa A, Tomoike H, Nakamura M (1990) Abrupt onset of coronary spasm causes progress of organic stenosis, and prolonged coronary spasm induces acute myocardial infarction (abstract No.0814; in Japanese). Jpn Circ J (Suppl) 54: 206Google Scholar
  69. 69.
    Ohara Y, Tagawa H, Kuga T, Tomoike H, Nakamura M (1989) Augumentation of serotonin-induced coronary constriction in respiratory or metabolic alkalosis in miniature pigs (abstract). Circulation 80 (Suppl II): 234Google Scholar
  70. 70.
    Gimbrone Jr, Obin MS, Brock AF, Luis EA, Hass PE, Hebert CA, Yip YK, Leung DW, Kohr WJ, Darbonne WC, Bechtol KB, Baker JB (1989) Endothelial interleukin-8: A novel inhibitor of leukocyte-endothelial interactions. Science 246: 1601–1603PubMedGoogle Scholar
  71. 71.
    Bassenge E, Busse R (1988) Endothelial modulation of coronary tone. Prog Cardiovasc Dis 30: 349–380PubMedGoogle Scholar
  72. 72.
    Ginsburg R, Bristow MB, Davis K, Dibiase A, Billingham ME (1984) Quantitative pharmacologic responses of normal and atherosclerotic isolated human epicardial coronary arteries. Circulation 69: 430–440PubMedGoogle Scholar
  73. 73.
    Henry PD, Yokoyama M (1980) Supersensitivity of atherosclerotic rabbit aorta to ergonovine. J Clin Invest 66: 306–313PubMedGoogle Scholar
  74. 74.
    Freedman B, Richmond DR, Kelley DT (1982) Pathophysiology of coronary artery spasm. Circulation 66: 705–709PubMedGoogle Scholar
  75. 75.
    Yamamoto Y, Tomoike H, Egashira K, Nakamura M (1987) Attenuation of endothelium-related relaxation and enhanced responsiveness of vascular smooth muscle to histamine in spastic coronary arterial segments from miniature pigs. Circ Res 61: 772–778PubMedGoogle Scholar
  76. 76.
    Förstermann U, Mügge A, Alheid U, Haverich A, Frolich J (1988) Selective attenuation of endothelium-mediated vasodilation in atherosclerotic human coronary arteries. Circ Res 62: 185–190PubMedGoogle Scholar
  77. 77.
    Toda N, Okamura T (1989) Endothelium-dependent and-independent responses to vasoactive substances of isolated human coronary arteries. Am J Physiol 257: H988–995PubMedGoogle Scholar
  78. 78.
    Harrison DG, Armstrong ML, Freiman PC, Heisted DD (1987) Restoration of endothelium dependent relaxation by dietary treatment of atherosclerosis. J Clin Invest 80: 1808–1811PubMedGoogle Scholar
  79. 79.
    Tagawa H, Tomoike H, Nakamura M: Putative mechanisms of endothelium-depend relaxation of aorta in the prescence of atheromatous plaque in hereditary hyperlipidemic rabbits. Circ. Res., in pressGoogle Scholar
  80. 80.
    Satoh S, Tomoike H, Mitsuoka W, Egashira S, Tagawa H, Kuga T, Nakamura M (1990) Smooth muscles from the spastic coronary artery segments shows hyper-contractility to histamine. Am J Physiol, 259: H9–H13PubMedGoogle Scholar
  81. 81.
    Stein I (1949) Observations on the action of ergonovine on the coronary circulation and its use in the diagnosis of coronary artery insufficiency. Am Heart J 37: 36–45PubMedGoogle Scholar
  82. 82.
    Schroeder JS, Bolen JL, Quint RA, Clark DA, Hayden WG, Higgins CB, Wexler L (1977) Provocation of coronary spasm with ergonovine maleate. New test with results in 57 patients undergoing coronary arteriography. Am J Cardiol 40: 487–491Google Scholar
  83. 83.
    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: 955–963PubMedGoogle Scholar
  84. 84.
    Yamamoto M, Katayama S (1968) Angina pectoris induced by marked vagotonic state (abstract). Jpn Circ J 32: 1856Google Scholar
  85. 85.
    Torii S, Araki Y, Sagara T, Kakimaru S, Kanaya H, Naito S, Nakagaki O (1974) Provocation of coronary spasm by subcutaneous administration of pilocarpine (in Japanese). Heart 6: 338–346Google Scholar
  86. 86.
    Endo M, Hirosawa K, Kaneko N, Hase K, Inoue Y, Konno S (1976) Prinzmetal’s variant angina: Coronary arteriogram and left ventriculogram during anginal attack induced by methacholine. N Engl J Med 294: 252–255PubMedGoogle Scholar
  87. 87.
    Ginsburg R, Bristow MR, Kantrowitz N, Baim DS, Harrison DC (1981) Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris. Am Heart J 102: 819–822PubMedGoogle Scholar
  88. 88.
    Yasue H, Nagano M, Omoto S, Takizawa A, Miwa K, Tanaka S (1978) Coronary arterial spasm and Prinzmetars variant form of angina induced by hyperventilation and tris-buffer infusion. Circulation 58: 56–62PubMedGoogle Scholar
  89. 89.
    Clark DA, Quint RA, Mitchell RL, Angell WW (1977) Coronary artery spasm; medical management, surgical denervation, and autotransplantation. J Thorac Cardiovasc Surg 73: 332–339PubMedGoogle Scholar
  90. 90.
    Bertrand ME, Lablanche JM, Tilmant PY, Ducloux G, Warembourg Jr H, Soots G (1981) Complete denevation of the heart (autotransplantation) for treatment of severe, refractory coronary spasm. Am J Cardiol 47(6): 1375–1378PubMedGoogle Scholar
  91. 91.
    Buda AJ, Fawles RE, Schroeder JS, Hunt SA, Cipriano PR, Stinson EB, Harrison DC (1981) Coronary artery spasm in the denervated transplanted human heart. Am J Med 70: 1144–1149PubMedGoogle Scholar
  92. 92.
    Betrin A, Pomar JL, Bourassa MG, Grondin CM (1983) Influence of partial sympathetic denevation on the results of myocardial revascularization in variant angina. Am J Cardiol 51: 661–667Google Scholar
  93. 93.
    Yamamoto Y, Tomoike H, Egashira K, Kobayashi T, Kawasaki T, Nakamura M (1987) Pathogenesis of coronary artery spasm in miniature swine with regional intimal thickening after balloon denudation. Circ Res 60: 113–121PubMedGoogle Scholar
  94. 94.
    Pitt B, Elliot EC, Gregg DE (1967) Adrenergic receptor activity in the coronary arteries of the unanesthetized dog. Circ Res 21: 75–84PubMedGoogle Scholar
  95. 95.
    Vatner SF, Higgins CB, Braunwald E (1974) Effects of norepinephrine on coronary circulation and left ventricular dynamics in the conscious dog. Circ Res 34: 812–823PubMedGoogle Scholar
  96. 96.
    Mohrman DF, Feigl EO (1978) Competition between sympathetic vasoconstriction and metabolic vasodilation in the canine coronary circulation. Circ Res 42: 79–86PubMedGoogle Scholar
  97. 97.
    Winniford MD, Filipchuk N, Hillis LD (1983) Alpha-adrenergic blockade for variant angina: A long term double-blind randomized trial. Circulation 67: 1185–1188PubMedGoogle Scholar
  98. 98.
    Chierchia S, Davies G, Berkenboom G, Crea F, Crean R, Maseri A (1984) Alpha-Adrenergic receptors and coronary spasm; An elusive link. Circulation 69: 8–14PubMedGoogle Scholar
  99. 99.
    Robertson D, Robertson RM, Niew AS, Oates JA, Friesinger GC (1979) Variant angina pectoris; Investigation of indexes of sympathetic nervous system function. Am J Cardiol 43: 1080–1085PubMedGoogle Scholar
  100. 100.
    Vatner SF, Hinze T (1983) Mechanism of constriction of large arteries by beta-adrenergic receptor blockade.Circ Res 53: 389–400PubMedGoogle Scholar
  101. 101.
    Nakamura M, Koiwaya Y (1979) Beneficial effect of diltiazem, a new antianginal drug, on angina pectoris at rest. Jpn Heart J 20: 613–621PubMedGoogle Scholar
  102. 102.
    Young MA, Knight DR, Vatner SF (1987) Autonomic control of large coronary arteries and resistance vessels. Prog Cardiovasc Dis 30: 211–234PubMedGoogle Scholar
  103. 103.
    Cohen RA (1985) Platelet-induced neurogenic coronary constriction due to accumulation of the false neurotransmitter, 5-hydroxytryptamine. J Clin Invest 75: 286–292PubMedGoogle Scholar
  104. 104.
    Denn MG, Stone HL (1976) Autonomic innervation of dog coronary arteries. J Appl Physio 41: 30–35Google Scholar
  105. 105.
    Kalsner S (1989) Cholinergic constriction in the general circulation and its role in coronary artery spasm. Circ Res 65: 237–257PubMedGoogle Scholar
  106. 106.
    Hirsch EF, Borghard-Erdle AM (1961) The innervation of human heart. I. coronary arteries and the myocardium. Arch Pathol 71: 384–407Google Scholar
  107. 107.
    Kalsner S (1985) Coronary artery reactivity in human vessels; some questions and some answers. Fed Proc 44: 321–325PubMedGoogle Scholar
  108. 108.
    Vanhoutte PM, Verbeuren TJ, Webb RC (1981) Local modulation of adrenergic neuroeffector interaction in the blood vessel wall. Physiol Rev 61: 151–247PubMedGoogle Scholar
  109. 109.
    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: 1046–1051PubMedGoogle Scholar
  110. 110.
    Furchgott RF, Zawadski JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373–376PubMedGoogle Scholar
  111. 111.
    Toda N (1983) Isolated human coronary arteries in response to vasoconstrictor substances. Am J Physiol 245: H937–H941PubMedGoogle Scholar
  112. 112.
    Kalsner S (1985) Cholinergic mechanisms in human coronary artery preparations: Implications of species differences. J Physiol 358: 509–526PubMedGoogle Scholar
  113. 113.
    Ginsburg R, Bristow MR, Harrison DC, Stinson EB (1980) Studies with isolated human coronary arteries. Chest 78 (Suppl): 180–186PubMedGoogle Scholar
  114. 114.
    Moummi G, Magous R, Strosberg D, Bali JP (1988) Muscarinic receptors in isolated smooth muscle cells from gastric antrum. Biochem Pharmacol 37: 1363–1369PubMedGoogle Scholar
  115. 115.
    EL-Ackad TM, Brody MJ (1975) Evidence for non-mast cell histamine in the vascular wall. Blood Vessels 12: 181–191PubMedGoogle Scholar
  116. 116.
    Garland CJ, Keatinge WR (1982) Constrictor actions of acetylcholine, 5-hydroxytryptamine and histamine on bovine coronary artery inner and outer muscle. J Physiol 327: 363–376PubMedGoogle Scholar
  117. 117.
    Howland RD, Spector S (1972) Disposition of histamine in mammalian blood vessels. J Pharmacol Exp Therap 182: 239–245Google Scholar
  118. 118.
    Kalsner S, Richards R (1984) Coronary arteries of cardiac patients are hyperreactive and contain stores of amines: A mechanism for coronary spasm. Science 223: 1435–1437PubMedGoogle Scholar
  119. 119.
    Gill DS, Barradas MA, Tonesca VA, Gracey L, Dandona P (1988) Increased histamine content in leukocytes and platelets of patients with peripheral vascular disease. Am J Clin Path 89: 622–626PubMedGoogle Scholar
  120. 120.
    McNicol A, Saxena SP, Brandes LJ, Gerrad JM (1989) A role of intracellular histamine in ultrastructural changes induced in platelets by phorbol esters. Arteriosclerosis 9: 684–689PubMedGoogle Scholar
  121. 121.
    Forman MB, Oates JA, Robertson D, Rabertson RM, Roberts, LJ II, Virmani R (1985) Increased adventitial mast cells in a patient with coronary spasm. N Engl J Med 313: 1138–1141PubMedGoogle Scholar
  122. 122.
    Ginsburg R, Bristow MR, Stinson EB, Harrison DC (1980) Histamine receptors in the human heart. Life Sci 26: 2245–2249PubMedGoogle Scholar
  123. 123.
    Shimokawa H, Okamatsu S, Taira Y, Nakamura M (1987) Cimetidine induces coronary artery spasm in patients with vasospastic angina. Can J Cardiol 3: 177–182PubMedGoogle Scholar
  124. 124.
    Curry RC, Pepine Jr CJ, Sabom MB, Conti CR (1979) Similarities of ergonovine-induced and spontaneous attacks of variant angina. Circulation 59: 307–312PubMedGoogle Scholar
  125. 125.
    Brazenor RM, Angus JA (1981) Ergometrine contracts isolated canine coronary arteries by serotonergic mechanism; no role for alpha adrenoceptors. J Pharmacol Exp Therap 218: 530–536Google Scholar
  126. 126.
    Holtz J, Held W, Sommer O, Kuhne G, Bassenge E (1982) Ergonovine induced constriction of epicardial coronary arteries in conscious dogs: Alpha-adrenoreceptors are not involved. Basic Res Cardiol 77: 278–291PubMedGoogle Scholar
  127. 127.
    Runbanyi GM, Frye RL, Holmes DR, Vanhoutte PM (1987) Vasoconstrictor activity of coronary sinus plasma from patients with coronary artery disease. J Am Coll Cardiol 9: 1243–1249Google Scholar
  128. 128.
    van den Berg EK, Schmitz JM, Benedict CR, Malloy CR, Willerson JT, Dehmer GJ (1989) Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology. Circulation 79: 116–124PubMedGoogle Scholar
  129. 129.
    Steele PP, Weily HS, Davise H, Genton E (1973) Platelet function studies in coronary artery disease. Circulation 48: 1194–1200PubMedGoogle Scholar
  130. 130.
    Ritchie JL, Harker LA (1977) Platelet and fibrinogen survival in coronary atherosclerosis; response of medical and surgical therapy. Am J Cardiol 39: 595–598PubMedGoogle Scholar
  131. 131.
    Horlick L (1961) Platelet adhesiveness in normal persons and subjects with atherosclerosis: Effect of high fat meals and anticoagulants on the adhesive index. Am J Cardiol 8: 459–470Google Scholar
  132. 132.
    Gormsen J, Nielsen JD, Andersen LA (1977) ADP-induced platelet aggregation in vitro in patients with ischemic heart disease and peripheral thromboatherosclerosis. Acta Med Scand 201: 509–513PubMedGoogle Scholar
  133. 133.
    Smitherman TC, Milam M, Woo J, Willerson JT, Frenkel UP (1981) Elevated beta-thromboglobulin in peripheral venous blood of patients with acute myocardial ischemia; direct evidence for enhanced platelet reactivity in vivo. Am J Cardiol 48: 395–402PubMedGoogle Scholar
  134. 134.
    Sobel M, Salzman EW, Davies GC, Handin RI, Sweeney J, Ploretz J, Kurland G (1981) Circulating platelet products in unstable angina pectoris. Circulation 63: 300–306PubMedGoogle Scholar
  135. 135.
    Schwartz MB, Hawiger J, Timmons S, Friesinger GC (1980) Platelet aggregates in blood from patients with ischemic heart disease. Thromb Haemost 43: 185–188PubMedGoogle Scholar
  136. 136.
    Chierchia S, DeCaterina R, Crea F, Patrono C, Maseri A (1982) Failure of thromboxane A2 blockade to prevent attacks of vasospastic angina. Circulation 66: 702–705PubMedGoogle Scholar
  137. 137.
    Robertson RM, Robertson D, Roberts LJ, Maas RL, Fitzgerald GA, Friesinger GC, Oates JA (1981) Thromboxane A2 in vasotonic angina pectoris: Evidence from direct measurements and in hibitor trials. N Engl J Med 304: 998–1003PubMedGoogle Scholar
  138. 138.
    Yui Y, Hattori R, Takatsu Y, Kawai C (1986) Selective thromboxane A2 synthetase inhibition in vasospastic angina pectoris. J Am Coll Cardiol 7: 25–29PubMedGoogle Scholar
  139. 139.
    Chierchia S, Patrono C, Crea F, Ciabattoni G, Decaterina R, Cinotti GA, Distante A, Maseri A (1982) Effects of intravenous prostacyclin in variant angina. Circulation 65: 470–477PubMedGoogle Scholar
  140. 140.
    Freedman SB, Chierchia S, Rodriguez-Plaza L, Bugiardini R, Smith G, Maseri A (1984) Ergonovine induced myocardial ischemia: No role for serotonergic receptors. Circulation 70: 178–183PubMedGoogle Scholar
  141. 141.
    Caterin RD, Capeggiani C, L’Abbate A (1984) A double-blind, placebo-controlled study of ketanserin in patients with Prinzmetal’s angina: Evidence against a role of serotonin in the genesis of coronary vasospasm. Circulation 69: 889–894Google Scholar
  142. 142.
    Vanhoutte PM, Shimokawa H (1989) Endothelium-derived relaxing factor and coronary spasm. Circulation 80: 1–9PubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • M. Nakamura
    • 1
  1. 1.Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of MedicineKyushu UniversityHigashi-ku, Fukuoka, 812Japan

Personalised recommendations