title: In vivo dynamic real-time monitoring and quantification of platelet-thrombus formation: use of a local isotope detector.
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 (111)In-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 (platelets x minutes x 10(6)), 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 (platelets x 10(6) 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.
authors.affiliation: Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Zaman
authors.forename: J I
authors.initials: JI
authors.lastname: Osende
authors.forename: J H
authors.initials: JH
authors.lastname: Chesebro
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: A
authors.initials: A
authors.lastname: Padurean
authors.forename: R
authors.initials: R
authors.lastname: Gallo
authors.forename: S G
authors.initials: SG
authors.lastname: Worthley
authors.forename: G
authors.initials: G
authors.lastname: Helft
authors.forename: O X
authors.initials: OX
authors.lastname: Rodriguez
authors.forename: J T
authors.initials: JT
authors.lastname: Fallon
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000502:physiology*; D020212:Carotid Artery Injuries / Q000000981:diagnostic imaging / Q000503:physiopathology; D003199:Computer Systems; D005343:Fibrinolytic Agents / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D007205:Indium Radioisotopes; D010314:Partial Thromboplastin Time; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011877:Radionuclide Imaging / Q000295:instrumentation / Q000379:methods; D013552:Swine; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D018608:Ultrasonography, Doppler; D014530:Uridine Diphosphate / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007205:Indium Radioisotopes; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014530:Uridine Diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006493:Heparin; D001241:Aspirin; D014544:Uridine Triphosphate