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

Microcirculation. 2012 Feb;19(2):143-54. doi: 10.1111/j.1549-8719.2011.00138.x.

Abstract

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.

MeSH terms

  • Actins / metabolism
  • Animals
  • Arterioles / metabolism
  • Arterioles / pathology
  • Arterioles / physiopathology
  • Capillaries / metabolism
  • Capillaries / pathology
  • Capillaries / physiopathology
  • Cattle
  • Cell Degranulation
  • Hemostatics / pharmacology*
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Ischemia / physiopathology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Male
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Reperfusion
  • Thrombin / pharmacology*

Substances

  • Actins
  • Hemostatics
  • Thrombin