RESUMO
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.
Assuntos
Alprostadil/farmacologia , Endotélio Vascular/efeitos dos fármacos , Fibrinolíticos/farmacologia , Heparina/farmacologia , Microcirculação/efeitos dos fármacos , Retalhos Cirúrgicos/irrigação sanguínea , Trombose/sangue , Ativador de Plasminogênio Tipo Uroquinase/farmacologia , Animais , Relação Dose-Resposta a Droga , Orelha Externa/irrigação sanguínea , Microscopia de Vídeo , Coelhos , Espécies Reativas de Oxigênio/toxicidade , Resultado do TratamentoRESUMO
Wound healing is a complex biologic process with initial inflammation, granulation tissue formation, and matrix remodeling. We observed the relation between angiostatic effects and corticosteroid administration time in the rabbit ear chamber. Angiogenesis in the chamber was studied using a microscope-television system. Two experiments were undertaken to represent the systemic and the topical administration of steroids. In experiment 1, 10 mg of triamcinolone acetonide was injected three times intramuscularly (on the day of implantation of the chamber, and the 7th and 14th day after implantation). Vascularization in this group was significantly delayed at the 7th, 14th, and 21st days but no difference from controls was observed in the size and density of vessels after its completion. In experiment 2, 3 mg of triamcinolone acetonide was injected once into the skin adjacent to the chamber on the 10th day after installment of chambers or on the day of installment. In the former group, new vascular growth was delayed until the 21st day after installment. The hemorrhagic zone had narrowed and vascular dilation was observed. In the latter group, endothelial budding was delayed and vascular constriction occurred. New vascular growth was severely delayed and granulation filling of the chamber was not completed. These results suggest not only that the topical administration had the stronger inhibitory effect on neovascularization than the systemic administration but that the effect differed depending on the stage of wound healing. In view of this effect of this steroid, we should pay careful attention to the time when steroids are administered to patients.