This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Montalescot, G. Articles by Grosgogeat, Y. Search for Related Content PubMed PubMed Citation Articles by Montalescot, G. Articles by Grosgogeat, Y.

Circulation, Vol 84, 2054-2062, Copyright © 1991 by American Heart Association

ARTICLES

Evaluation of thromboxane production and complement activation during myocardial ischemia in patients with angina pectoris

G Montalescot, G Drobinski, J Maclouf, F Maillet, J Salloum, A Ankri, M Kazatchkine, L Eugene, D Thomas and Y Grosgogeat
Department of Cardiology, Hopital Pitie-Salpetriere, Paris, France.

BACKGROUND. The complement system and arachidonic acid metabolites are involved in severe myocardial ischemia such as myocardial infarction. Furthermore, there is experimental evidence for C5a participation in thromboxane production. METHODS AND RESULTS. We examined whether C5a and thromboxane are produced during brief and reversible episodes of myocardial ischemia induced in patients with stable angina. Twenty-five patients underwent either atrial pacing or percutaneous transluminal coronary angioplasty associated with arterial and coronary sinus blood sampling. Rapid atrial stimulation of patients with effort angina caused significant ST segment depression (delta ST = -1.7 +/- 0.2 mm), decreased fractional lactate extraction (from +12.8 +/- 2.5% baseline to -13.7 +/- 4.6% at peak ischemia, n = 13, p less than 0.001), and increased coronary sinus plasma thromboxane B2 levels (from 345 +/- 85 pg/ml baseline to 1,684 +/- 64 pg/ml at peak ischemia, p less than 0.01). Changes of fractional lactate extraction correlated significantly with changes of coronary sinus plasma levels of thromboxane B2. There was no change of coronary sinus 6-keto-PGF1 alpha levels. Similar pacing of control subjects (n = 6) did not cause release of lactate or thromboxane. Seventeen other patients underwent exercise testing with noninvasive measurements of thromboxane and prostacyclin metabolites in urinary samples collected before and after the test. No detectable increase of urinary 11-dehydrothromboxane B2 was measured in patients with stable angina after exercise-induced myocardial ischemia. However, basal 11-dehydrothromboxane B2 levels were significantly higher in patients with angina (105 +/- 25 pg/mmol creatinine, n = 9) than in control patients (45 +/- 8 pg/mmol creatinine, n = 8, p less than 0.05 between groups). Coronary sinus plasma levels of the anaphylatoxin C5a always remained below 4 ng/ml in patients undergoing pacing. More severe myocardial ischemia after coronary angioplasty (percent lactate extraction decreased from +24.8 +/- 2.7% baseline to -41.6 +/- 22.4% at peak ischemia, p less than 0.05) was not associated with C3a or C5b-9 generation. In all patients, there was neither platelet sequestration nor platelet alpha-granule release (no changes of beta-thromboglobulin/platelet factor 4 levels) into the coronary sinus plasma. CONCLUSIONS. Patients with stable angina have chronically increased thromboxane synthesis as assessed by excretion of urinary metabolites. Thromboxane is acutely released into the coronary sinus during pacing-induced ischemia without significant intracoronary platelet aggregation. Complement does not appear to be activated in stable angina during brief and reversible episodes of myocardial ischemia and does not contribute to thromboxane production.

This article has been cited by other articles:

				S. S. Jolly, J. Pogue, K. Haladyn, R. J.G. Peters, K. A.A. Fox, A. Avezum, B. J. Gersh, H. J. Rupprecht, S. Yusuf, and S. R. Mehta Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study Eur. Heart J., April 2, 2009; 30(8): 900 - 907. [Abstract] [Full Text] [PDF]

				S. R. Steinhubl, D. L. Bhatt, D. M. Brennan, G. Montalescot, G. J. Hankey, J. W. Eikelboom, P. B. Berger, E. J. Topol, and on behalf of the CHARISMA Investigators Aspirin to Prevent Cardiovascular Disease: The Association of Aspirin Dose and Clopidogrel With Thrombosis and Bleeding Ann Intern Med, March 17, 2009; 150(6): 379 - 386. [Abstract] [Full Text] [PDF]

				C. L. Campbell, S. Smyth, G. Montalescot, and S. R. Steinhubl Aspirin Dose for the Prevention of Cardiovascular Disease: A Systematic Review JAMA, May 9, 2007; 297(18): 2018 - 2024. [Abstract] [Full Text] [PDF]

				R. Jaumdally, C. Varma, R. J. Macfadyen, and G. Y.H. Lip Coronary sinus blood sampling: an insight into local cardiac pathophysiology and treatment? Eur. Heart J., April 2, 2007; 28(8): 929 - 940. [Abstract] [Full Text] [PDF]

				M. J. Wacker, S. R. Best, L. M. Kosloski, C. J. Stachura, R. L. Smoot, C. B. Porter, and J. A. Orr Thromboxane A2-induced arrhythmias in the anesthetized rabbit Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1353 - H1361. [Abstract] [Full Text] [PDF]

				M. J. Wacker, H. L. Wilhelm, S. E. Gomez, E. Floor, and J. A. Orr Role of serotonin in thromboxane A2-induced coronary chemoreflex Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H867 - H875. [Abstract] [Full Text] [PDF]

				M. J. Wacker, R. N. Tehrani, R. L. Smoot, and J. A. Orr Thromboxane A2 mimetic evokes a bradycardia mediated by stimulation of cardiac vagal afferent nerves Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H482 - H490. [Abstract] [Full Text] [PDF]