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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:860.)
© 2000 American Heart Association, Inc.

Thrombosis

In Vivo Dynamic Real-Time Monitoring and Quantification of Platelet-Thrombus Formation

Use of a Local Isotope Detector

Azfar G. Zaman; Julio I. Osende; James H. Chesebro; Valentin Fuster; Adrian Padurean; Richard Gallo; Stephen G. Worthley; Gerard Helft; Oswaldo X. Rodriguez; John T. Fallon; Juan J. Badimon

From the Cardiovascular Biology Research Laboratory (A.G.Z., J.I.O., V.F., S.G.W., G.H., O.X.R., J.J.B.), Zena and Michael A. Wiener Cardiovascular Institute (J.H.C., V.F., J.J.B.), and the Department of Pathology (J.T.F.), Mount Sinai School of Medicine, New York, NY; Regions Hospital (A.P.), St. Paul, Minn; and Montreal Heart Institute (R.G.), Montreal, Canada.

Correspondence to Dr J.J. Badimon, Director, Cardiovascular Biology Research Laboratory, Zena and Michael A. Wiener Cardiovascular Institute, Box 1030, Mount Sinai School of Medicine, New York, NY 10029-6574. E-mail jbadimo{at}smtplink.mssm.edu

Abstract—Current methods for monitoring thrombosis and thrombus growth are invasive and provide only single–time-point data. Animal models rely mainly on flow changes as a surrogate of thrombus formation. Our aim was to validate a unique potentially noninvasive system to detect and quantify dynamic thrombus formation in vivo by using a porcine model of carotid artery injury. Thrombus growth was monitored by deposition of autologous ¹¹¹In-labeled platelet activity over the injured artery by use of miniaturized gamma detectors and Doppler blood flow. Counts were recorded at 2-minute intervals for 2 hours. The technique was validated by comparing standard antithrombotic agents against controls. Platelet recruitment was detected before significant change in flow. Thrombus formation, calculated as the area under the curve (plateletsxminutesx10⁶), was greatest for control animals (11.7±1.28), followed by animals treated with aspirin (6.13±0.91, P<0.05), heparin (2.45±0.34, P<0.05), and hirudin (0.2±0.01, P<0.01 compared with heparin). The rate of platelet deposition was assessed as the slope of the curve in the first 30 minutes (plateletsx10⁶ per minute) for the following treatment groups of animals: control, 3.53±0.34; aspirin, 1.67±0.34 (P<0.01); heparin, 1.55±0.3 (P<0.01); and hirudin, 0.25±0.03 (P<0.001). There was no statistical difference between heparin and aspirin treatments. Change in flow was assessed as reduction from baseline: control, >99±0.34%; aspirin, 39±9.1%; heparin, 36±12.5%; and hirudin, 17±5.4%. There was no statistical difference between the aspirin- and heparin-treated groups. Morphometric analysis revealed >99±0.63% occlusion of the luminal area with thrombus for the control group, 43±14.3% for the aspirin-treated group, 30±5.6% for the heparin-treated group, and <10±1.8% for the hirudin-treated group. Assessment of platelet-thrombus formation with this technique was more sensitive than change in flow in determining antithrombotic efficacy, and thrombus formation was detected earlier. This study validates a new quantitative, sensitive, potentially noninvasive, portable, in vivo monitoring of dynamic thrombus growth, which appears applicable to phase II studies in humans.

Key Words: platelets • thrombus • antithrombotics • radioisotopes

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