Exogenous Thrombin Delivery Promotes Collateral Capillary Arterialization and Tissue Reperfusion in the Murine Spinotrapezius Muscle Ischemia Model

摘要

Objective: We examined the effects of exogenously delivered thrombin on cell recruitment in skeletal muscle and the formation of new collateral arterioles in the microvasculature in response to ligation-induced ischemia. Methods: Thrombin or vehicle was locally applied to both ligated and nonoperated Balb/c spinotrapezius muscles, which were harvested after three or seven days, imaged using confocal microscopy, and analyzed. Results: Thrombin treatment resulted in accelerated arterialization of collateral capillaries and accelerated tissue reperfusion in ischemic muscles. Uninjured muscle treated with thrombin displayed increased vascular cell adhesion molecule 1 expression on arteriole and venule endothelium, increased expression of smooth muscle α-actin on capillary-sized vessels, increased infiltration by CD11b + leukocytes, and mast cell infiltration and degranulation. Conclusions: Exogenous delivery of thrombin enhances microvascular collateral development in response to ischemic insult, and accelerates tissue reperfusion. Elicited responses from multiple cell types probably contribute to these effects.