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Circulation. 1989;80:198-205

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Circulation, Vol 80, 198-205, Copyright © 1989 by American Heart Association


ARTICLES

Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications

JT Willerson, P Golino, J Eidt, WB Campbell and LM Buja
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9047.

We have speculated previously that the abrupt conversion from chronic stable to unstable angina and the continuum to acute myocardial infarction may result from myocardial ischemia caused by progressive platelet aggregation and dynamic vasoconstriction themselves caused by local increases in thromboxane and serotonin at sites of coronary artery stenosis and endothelial injury. Platelet aggregation and dynamic coronary artery vasoconstriction probably result from the local accumulation of thromboxane and serotonin and also relative decreases in the local concentrations of endothelially derived vasodilators and inhibitors of platelet aggregation, such as endothelium-derived relaxing factor (EDRF) and prostacyclin. With severe reductions in coronary blood flow caused by these mechanisms, platelet aggregates may increase, and an occlusive thrombus composed of platelets and white and red blood cells in a fibrin mesh may develop. When coronary arteries are occluded or narrowed for a sufficient period of time by these mechanisms, myocardial necrosis, electrical instability, or sudden death may occur. We believe that unstable angina and acute myocardial infarction are a continuum in relation to the process of coronary artery thrombosis and vasoconstriction. When the period of platelet aggregation or dynamic vasoconstriction at sites of endothelial injury and coronary artery stenosis is brief, unstable angina or non-Q wave infarction may occur. However, when the coronary artery obstruction by these mechanisms is prolonged for several hours, Q wave myocardial infarction results. Chronic endothelial injury and coronary artery stenosis are probably associated with the accumulation of platelets, white and red blood cells, and a fibrin mesh at the site of stenosis and endothelial injury.


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F. Cipollone, P. Patrignani, A. Greco, M. R. Panara, R. Padovano, F. Cuccurullo, C. Patrono, A. G. Rebuzzi, G. Liuzzo, G. Quaranta, et al.
Differential Suppression of Thromboxane Biosynthesis by Indobufen and Aspirin in Patients With Unstable Angina
Circulation, August 19, 1997; 96(4): 1109 - 1116.
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M. D. Guazzi, M. Bussotti, L. Grancini, N. De Cesare, M. Guazzi, I. L. Pera, and A. Loaldi
Evidence of Multifocal Activity of Coronary Disease in Patients With Acute Myocardial Infarction
Circulation, August 19, 1997; 96(4): 1145 - 1151.
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StrokeHome page
S. A. Mousa, D.-X. Mu, and B. R. Lucchesi
Prevention of Carotid Artery Thrombosis by Oral Platelet GPIIb/IIIa Antagonist in Dogs
Stroke, April 1, 1997; 28(4): 830 - 836.
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G. G. Neri Serneri, D. Prisco, F. Martini, A. Gori, T. Brunelli, L. Poggesi, C. Rostagno, G. F. Gensini, and R. Abbate
Acute T-Cell Activation Is Detectable in Unstable Angina
Circulation, April 1, 1997; 95(7): 1806 - 1812.
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T. Ueyama, H. Ikeda, N. Haramaki, K. Kuwano, and T. Imaizumi
Effects of Monoclonal Antibody to P-Selectin and Analogue of Sialyl Lewis X on Cyclic Flow Variations in Stenosed and Endothelium-Injured Canine Coronary Arteries
Circulation, March 18, 1997; 95(6): 1554 - 1559.
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J. Pharmacol. Exp. Ther.Home page
J.-P. Valentin, S. Vieu, F. Bertolino, P. Fauré, and G. W. John
Differential Involvement of Serotonin 2A/C and Thromboxane A2/Prostanoid Receptors in High- vs. Low-Shear Rate Arterial Thrombosis in Rabbits
J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 761 - 769.
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S. P. Schulman, P. J. Goldschmidt-Clermont, E. J. Topol, R. M. Califf, F. I. Navetta, J. T. Willerson, N. C. Chandra, A. D. Guerci, J. J. Ferguson, R. A. Harrington, et al.
Effects of Integrelin, a Platelet Glycoprotein IIb/IIIa Receptor Antagonist, in Unstable Angina: A Randomized Multicenter Trial
Circulation, November 1, 1996; 94(9): 2083 - 2089.
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J. T. Willerson
Inhibitors of Platelet Glycoprotein IIb/IIIa Receptors: Will They Be Useful When Given Chronically?
Circulation, September 1, 1996; 94(5): 866 - 868.
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T. Kadokami, K. Egashira, K. Kuwata, Y. Fukumoto, T. Kozai, H. Yasutake, T. Kuga, H. Shimokawa, K. Sueishi, and A. Takeshita
Altered Serotonin Receptor Subtypes Mediate Coronary Microvascular Hyperreactivityin Pigs With Chronic Inhibitionof Nitric Oxide Synthesis
Circulation, July 15, 1996; 94(2): 182 - 189.
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N. Maalej and J. D. Folts
Increased Shear Stress Overcomes the Antithrombotic Platelet Inhibitory Effect of Aspirin in Stenosed Dog Coronary Arteries
Circulation, March 15, 1996; 93(6): 1201 - 1205.
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C. W. White
Simplicity's Virtue Scorned : Precision Comes to TIMI Flow Grading and the Results Are . . . Surprising
Circulation, March 1, 1996; 93(5): 853 - 856.
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M. Gawaz, F.-J. Neumann, I. Ott, A. Schiessler, and A. Schomig
Platelet Function in Acute Myocardial Infarction Treated With Direct Angioplasty
Circulation, January 15, 1996; 93(2): 229 - 237.
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L. G. Frederick, O. D. Suleymanov, L. W. King, A. K. Salyers, N. S. Nicholson, and L. P. Feigen
The Protective Dose of the Potent GPIIb/IIIa Antagonist SC-54701A Is Reduced When Used in Combination With Aspirin and Heparin in a Canine Model of Coronary Artery Thrombosis
Circulation, January 1, 1996; 93(1): 129 - 134.
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L. Lacoste, J. Y.T. Lam, J. Hung, G. Letchacovski, C. B. Solymoss, and D. Waters
Hyperlipidemia and Coronary Disease : Correction of the Increased Thrombogenic Potential With Cholesterol Reduction
Circulation, December 1, 1995; 92(11): 3172 - 3177.
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H. Ikeda, Y. Takajo, K. Ichiki, T. Ueno, S. Maki, T. Noda, K. Sugi, and T. Imaizumi
Increased Soluble Form of P-Selectin in Patients With Unstable Angina
Circulation, October 1, 1995; 92(7): 1693 - 1696.
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E. Falk, P. K. Shah, and V. Fuster
Coronary Plaque Disruption
Circulation, August 1, 1995; 92(3): 657 - 671.
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Circ. Res.Home page
H. W. Mueller, C. A. Haught, J. M. McNatt, K. Cui, S. J. Gaskell, D. A. Johnston, and J. T. Willerson
Measurement of Platelet-Activating Factor in a Canine Model of Coronary Thrombosis and in Endarterectomy Samples From Patients With Advanced Coronary Artery Disease
Circ. Res., July 1, 1995; 77(1): 54 - 63.
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P. Theroux
Angiographic and Clinical Progression in Unstable Angina : From Clinical Observations to Clinical Trials
Circulation, May 1, 1995; 91(9): 2295 - 2298.
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J. A. Berliner, M. Navab, A. M. Fogelman, J. S. Frank, L. L. Demer, P. A. Edwards, A. D. Watson, and A. J. Lusis
Atherosclerosis: Basic Mechanisms : Oxidation, Inflammation, and Genetics
Circulation, May 1, 1995; 91(9): 2488 - 2496.
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F. Leya, J. Fareed, and J. Walenga
Acute Myocardial Infarction: Diagnosis and Management
Clinical and Applied Thrombosis/Hemostasis, March 1, 1995; 1(2): 160 - 165.
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A. M. Zeiher, H. Goebel, V. Schachinger, and C. Ihling
Tissue Endothelin-1 Immunoreactivity in the Active Coronary Atherosclerotic Plaque : A Clue to the Mechanism of Increased Vasoreactivity of the Culprit Lesion in Unstable Angina
Circulation, February 15, 1995; 91(4): 941 - 947.
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B. H. Annex, S. M. Denning, K. M. Channon, M. H. Sketch Jr, R. S. Stack, J. H. Morrissey, and K. G. Peters
Differential Expression of Tissue Factor Protein in Directional Atherectomy Specimens From Patients With Stable and Unstable Coronary Syndromes
Circulation, February 1, 1995; 91(3): 619 - 622.
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NEJMHome page
The EPIC Investigators
Use of a Monoclonal Antibody Directed against the Platelet Glycoprotein IIb/IIIa Receptor in High-Risk Coronary Angioplasty
N. Engl. J. Med., April 7, 1994; 330(14): 956 - 961.
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P. Golino, F. Piscione, C. R. Benedict, H. V. Anderson, M. Cappelli-Bigazzi, C. Indolfi, M. Condorelli, M. Chiariello, and J. T. Willerson
Local Effect of Serotonin Released during Coronary Angioplasty
N. Engl. J. Med., February 24, 1994; 330(8): 523 - 528.
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H. V. Anderson and J. T. Willerson
Thrombolysis in Acute Myocardial Infarction
N. Engl. J. Med., September 2, 1993; 329(10): 703 - 709.
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Y. Basaran, M.M. Basaran, K.F. Babacan, B. Ener, T. Okay, H. Gok, and M. Ozdemir
Serum Tumor Necrosis Factor Levels in Acute Myocardial Infarction and Unstable Angina Pectoris
Angiology, April 1, 1993; 44(4): 332 - 337.
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J. A. Ware and D. D. Heistad
Platelet-Endothelium Interactions
N. Engl. J. Med., March 4, 1993; 328(9): 628 - 635.
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