This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Shen, Y.-T. Articles by Gould, R. J. Search for Related Content PubMed PubMed Citation Articles by Shen, Y.-T. Articles by Gould, R. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID HEPARIN Medline Plus Health Information Blood Thinners Related Collections Arterial thrombosis Coagulation Platelet function inhibitors Coronary circulation Receptor pharmacology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2309.)
© 2000 American Heart Association, Inc.

Thrombosis

Platelet Glycoprotein IIb/IIIa Receptor Inhibitor Preserves Coronary Flow Reserve During Progressive Coronary Arteriostenosis in Swine

You-Tang Shen; Richard T. Wiedmann; Joseph J. Lynch, Jr; Robert J. Gould

From the Department of Pharmacology, Merck Research Laboratories, West Point, Pa.

Correspondence to You-Tang Shen, MD, Department of Pharmacology, Merck Research Laboratories, WP46-200, West Point, PA 19486. E-mail youtang_shen{at}merck.com

Abstract—Thrombosis resulting from blood platelet aggregation via glycoprotein (GP) IIb/IIIa receptor activation triggers the local release of vasoactive substances. Therefore, inhibition of these receptors could affect coronary vasoactive function during thrombotic coronary arteriostenosis. Twenty pigs were instrumented with an aortic catheter and with hydraulic occluders and flow probes on both the left anterior descending (LAD) and the left circumflex (LCx) coronary arteries. One of these 2 coronary arteries was repeatedly injured by external clamping for 15-second periods at 30-minute intervals while the pigs were given either a GP IIb/IIIa receptor inhibitor (L-739,758) (n=5), heparin (n=5), aspirin (n=3), or saline (n=7). There were no baseline differences between the 4 groups in mean arterial pressure, resting coronary blood flow (CBF), or reactive hyperemic response (RHR), which was induced by brief coronary artery occlusion and expressed as flow debt repayment. After multiple injuries, resting CBF had decreased by 95±2% (ie, nearly complete coronary artery occlusion) at 15±4 minutes in the control group, whereas in the heparin-, aspirin-, and GP IIb/IIIa inhibitor–treated groups, resting CBF had decreased by only 21±7% at 18±3 minutes, 15±3% at 18±5 minutes, and 15±7% at 21±4 minutes, respectively, suggesting that heparin, aspirin, and the GP IIb/IIIa inhibitor each prevented injury-induced coronary artery occlusion. After the initial injury, the RHR was progressively reduced in the control and heparin- and aspirin-treated groups but not in the GP IIb/IIIa inhibitor–treated group. At a comparable level of resting CBF (15% below baseline), the RHR was reduced more in the control (-56±9%), heparin-treated (-49±9%), and aspirin-treated (-61±12) groups (P<0.05) than in the GP IIb/IIIa inhibitor–treated group (-26±6%). When the resting CBF had decreased by 35%, the RHR still was reduced significantly more (P<0.01) in the heparin-treated group (-64±9%) than in the GP IIb/IIIa inhibitor–treated group (-21±6%). In a separate group of control pigs (n=4) subjected to 2 injuries, coronary perfusion pressure distal to the injury site was reduced by 14±1 mm Hg from the arterial pressure, and the RHR was 20±6%. When the distal coronary perfusion pressure was reduced similarly (-14±1 mm Hg) in a separate group of GP IIb/IIIa inhibitor–treated pigs (n=4) by 2 injuries and the use of a hydraulic occluder, the RHR was 130±16% (P<0.01 versus control). Our data demonstrate for the first time that a platelet GP IIb/IIIa receptor inhibitor can preserve the distal coronary vasodilatory response during progressive coronary arteriostenosis.

Key Words: coronary reactive hyperemia • coronary reserve • heparin • aspirin • coronary injury • glycoprotein IIb/IIIa

This article has been cited by other articles:

				H. Kunichika, O. Ben-Yehuda, S. Lafitte, N. Kunichika, B. Peters, and A. N. DeMaria Effects of glycoprotein iib/iiia inhibition on microvascular flow after coronary reperfusion: A quantitative myocardial contrast echocardiography study J. Am. Coll. Cardiol., January 21, 2004; 43(2): 276 - 283. [Abstract] [Full Text] [PDF]

				T. Heitzer, I. Ollmann, K. Koke, T. Meinertz, and T. Munzel Platelet Glycoprotein IIb/IIIa Receptor Blockade Improves Vascular Nitric Oxide Bioavailability in Patients With Coronary Artery Disease Circulation, August 5, 2003; 108(5): 536 - 541. [Abstract] [Full Text] [PDF]

				J. A. Barrabes, D. Garcia-Dorado, M. Mirabet, R.-M. Lidon, B. Soriano, M. Ruiz-Meana, P. Pizcueta, J. Blanco, Y. Puigfel, and J. Soler-Soler Lack of effect of glycoprotein IIb/IIIa blockade on myocardial platelet or polymorphonuclear leukocyte accumulation and on infarct size after transient coronary occlusion in pigs J. Am. Coll. Cardiol., January 2, 2002; 39(1): 157 - 165. [Abstract] [Full Text] [PDF]