Exogenous thrombin delivery promotes collateral capillary arterialization and tissue reperfusion in the murine spinotrapezius muscle ischemia model.

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.

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