(Circulation. 1995;91:1336-1340.)
© 1995 American Heart Association, Inc.
Articles |
Intravenous Cocaine Induces Platelet Activation in the Conscious Dog
From the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of the Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Mass (A.D.K., R.P.S., J.A.W.); the New England Regional Primate Research Center, Southborough, Mass (R.P.S.); and the Hematology Division, The Toronto Hospital, Toronto, Ontario (E.L.Y.).
Correspondence to J. Anthony Ware, MD, Cardiovascular Division, Beth Israel Hospital, 330 Brookline Ave, Boston, MA 02215.
Background Cocaine consumption has been associated with thrombosis of coronary and peripheral arteries. Since cocaine has been found to induce platelet activation in vitro, we sought to establish whether cocaine induced platelet activation in vivo.
Methods and Results Chronically instrumented, conscious dogs were infused with cocaine (1 mg/kg), norepinephrine (0.2 to 0.4 mg/kg), or saline intravenously over 1 minute. Activated canine platelets were identified in whole blood collected from an indwelling aortic catheter by flow cytometric detection of the binding of a monoclonal antibody directed against the activation-dependent antigen P-selectin. Infusion of cocaine resulted in an elevation of mean arterial pressure (91±3 to 128±7 mm Hg [P<.001]) and heart rate (87±9 to 125±11 beats per minute [P<.01]). A similar change (P=NS) in mean arterial pressure followed norepinephrine infusion (100±5 to 137±13 mm Hg [P<.04]), whereas saline infusion had no effect. Cocaine resulted in a substantial but delayed increase in platelet P-selectin expression (14±7% [P<.08], 31±12% [P<.04], and 55±22% [P<.04] at 17, 22, and 27 minutes after drug infusion, respectively). The magnitude of this increase was similar to that found in blood treated ex vivo with the agonists ADP or PAF (23±7% and 53±15%, respectively). No significant increase in P-selectin expression was detected in the blood of animals that received norepinephrine or saline. Serum cocaine concentrations were highest immediately after infusion (538±55 ng/mL at 2 minutes) but declined rapidly (185±22 and 110±25 ng/mL at 17 and 32 minutes after infusion); in contrast, the increase in benzoylecgonine concentrations was delayed (from <25 ng/mL in all but one animal [34 ng/mL] at 2 minutes to 46±4 and 71±11 ng/mL at 17 and 32 minutes, respectively, after infusion).
Conclusions Intravenous cocaine induces activation of individual circulating platelets; this effect is not reproduced by infusion of norepinephrine at doses sufficient to exert similar hemodynamic effects. The delay in detection of activated platelets after treatment with cocaine may result from the adhesion and subsequent detachment of activated platelets; alternatively, cocaine metabolites, rather than the drug itself, may induce platelet activation.
Key Words: cocaine • norepinephrine • proteins • cells
This article has been cited by other articles:
 |
|
 |
|
  S. D Treadwell and T. G Robinson Cocaine use and stroke Postgrad. Med. J., June 1, 2007; 83(980): 389 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Jaffe and P. L. Kimmel Chronic Nephropathies of Cocaine and Heroin Abuse: A Critical Review Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Egred and G K Davis Cocaine and the heart Postgrad. Med. J., September 1, 2005; 81(959): 568 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Satran, B. A. Bart, C. R. Henry, M. B. Murad, S. Talukdar, D. Satran, and T. D. Henry Increased Prevalence of Coronary Artery Aneurysms Among Cocaine Users Circulation, May 17, 2005; 111(19): 2424 - 2429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, Q. Ke, Y.-F. Xiao, G. Wu, E. Kaplan, T. G. Hampton, S. Malek, J.-Y. Min, I. Amende, and J. P. Morgan Cocaine and catecholamines enhance inflammatory cell retention in the coronary circulation of mice by upregulation of adhesion molecules Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2323 - H2331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kokado, M. Shimizu, H. Yoshio, H. Ino, K. Okeie, Y. Emoto, T. Matsuyama, M. Yamaguchi, T. Yasuda, N. Fujino, et al. Clinical Features of Hypertrophic Cardiomyopathy Caused by a Lys183 Deletion Mutation in the Cardiac Troponin I Gene Circulation, August 8, 2000; 102(6): 663 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Marder and I. K. Mellinghoff Cocaine and Buerger Disease: Is There a Pathogenetic Association? Arch Intern Med, July 10, 2000; 160(13): 2057 - 2060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C M Heesch, C R Wilhelm, J Ristich, J Adnane, F A Bontempo, and W R Wagner Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans Heart, June 1, 2000; 83(6): 688 - 695. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. W. Lipton, K. P. Mangan, and J. M. Silvestri Acute Cocaine Toxicity: Pharmacology and Clinical Presentations in Adult and Pediatric Populations Journal of Pharmacy Practice, April 1, 2000; 13(2): 159 - 169. [Abstract] [PDF]
|
|
|
|
 |
|
 E. J. Tanhehco, K. Yasojima, P. L. McGeer, and B. R. Lucchesi Acute Cocaine Exposure Up-Regulates Complement Expression in Rabbit Heart J. Pharmacol. Exp. Ther., January 1, 2000; 292(1): 201 - 208. [Abstract] [Full Text]
|
|
|
|
|
|
J. Sztajzel, F. Mach, and A. Righetti Current concepts in medicine: Role of the vascular endothelium in patients with angina pectoris or acute myocardial infarction with normal coronary arteries Postgrad. Med. J., January 1, 2000; 76(891): 16 - 21. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Mittleman, D. Mintzer, M. Maclure, G. H. Tofler, J. B. Sherwood, and J. E. Muller Triggering of Myocardial Infarction by Cocaine Circulation, June 1, 1999; 99(21): 2737 - 2741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Wilbert-Lampen, C. Seliger, T. Zilker, and R. M. Arendt Cocaine Increases the Endothelial Release of Immunoreactive Endothelin and Its Concentrations in Human Plasma and Urine : Reversal by Coincubation With {sigma}-Receptor Antagonists Circulation, August 4, 1998; 98(5): 385 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Hollander, D. E. Brooks, and S. M. Valentine Assessment of Cocaine Use in Patients With Chest Pain Syndromes Arch Intern Med, January 12, 1998; 158(1): 62 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Shannon, P. Lozano, Q. Cai, W. T. Manders, and Y.-t. Shen Mechanism of the Systemic, Left Ventricular, and Coronary Vascular Tolerance to a Binge of Cocaine in Conscious Dogs Circulation, August 1, 1996; 94(3): 534 - 541. [Abstract] [Full Text]
|
|