The features of thrombus in a microvessel injury model and the antithrombotic efficacy of heparin, urokinase, and prostaglandin E1.
In failed flap transfers and in burn injuries, superoxides and thrombi generated in the microcirculation are considered responsible for tissue injury. A dynamic and morphologic analysis of thrombus formation was conducted in a model of microvessel injury, and an analysis was made of the different antithrombotic effects of heparin, urokinase, and prostaglandin E(1). The dye-light method was used (i.e., injury of the endothelium by reactive oxygen species) to induce thrombus formation in both the arterioles and venules of the rabbit ear chamber under an intravital microscope-television system. The dynamic course of thrombus formation was observed, and the period from irradiation to complete obstruction of blood flow (i.e., time to stasis) was measured and compared in relation to various treatment conditions. Arteriolar thrombi were formed by platelet aggregation. Venular thrombi were composed of platelets and erythrocytes that gathered and adhered around leukocytes stuck to the vessel wall. Heparin treatment prolonged the time to stasis in both the arterioles and the venules. Urokinase extended the time to stasis in the venules but not in the arterioles. Prostaglandin E(1)-treatment significantly prolonged the time to stasis in the arterioles, but only high-dose prostaglandin E(1) prolonged the time to stasis in the venules. The results of this study show that endothelial damage caused by superoxides promotes the formation of thrombi that differ in composition between the arteriole and the venule and that the effectiveness of each drug varies accordingly. The authors believe that these agents can be used with increased efficacy if the two types of thrombi and the specific antithrombotic effects of each agent are considered.
Hashimoto
Ichiro
I
Department of Plastic and Reconstructive Surgery, The University of Tokushima School of Medicine, Japan. ichiro@clin.med.tokushima-u.ac.jp
Nakanishi
Hideki
H
Shono
Yoshitaka
Y
Yamano
Masahiro
M
Toda
Maki
M
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000098:blood supply; D004730:Endothelium, Vascular / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects*; D018715:Microscopy, Video; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000633:toxicity; D013524:Surgical Flaps / Q000098:blood supply*; D013927:Thrombosis / Q000097:blood*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D017382:Reactive Oxygen Species; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator; D000527:Alprostadil