Activated protein C attenuates microvascular injury during systemic hypoxia

Sonja Bartolome, John G. Wood, Alfred J. Casillan, Steven Q. Simpson, Amy R. O'Brien-Ladner

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


In response to hypoxia, an inflammatory cascade is initiated and microvascular injury ensues. Specifically, within 10 min, leukocyte adherence to the endothelium begins, and leukocyte emigration and vascular leak soon follow. Activated protein C (APC) has been reported to have both anticoagulant and anti-inflammatory properties. Activated protein C is best described in its role as a treatment for sepsis. However, it has been used, with some success, in experimental models of hypoxic injury. We hypothesized that APC would be protective against microvascular injury during systemic hypoxia. Randomized prospective animal study. Adult male Sprague-Dawley rats. To characterize the microvascular response to APC exposure during hypoxia, four rat groups were used: saline control, APC infusion alone (100 mg/kg bolus), hypoxia alone (10% O2), and simultaneous hypoxia + APC infusion. Measurements of leukocyte adherence (no. per 100-μm venule), leukocyte emigration (no. per 4,000 μm), and venular leak by fluorescein isothiacyanate-labeled albumin (Fo/Fi) were performed during intravital microscopy of the intact venular bed. Leukocyte adherence decreased from 14.5 (±1.2) cells/100-μm venule in hypoxic rats to 4.4 (±1.5) cells/100-μm venule in those treated with both hypoxic gas and APC infusion (P < 0.001). Similarly, leukocyte emigration in hypoxic rats reached 12.3 (± 2.2) cells/4,000-μm venule, but was reduced to 3.5 (±0.3) cells/4,000-μm venule (P <.001). Venular permeability to protein was also significantly decreased in the APC-treated group from 0.82 (±0.14) to 0.25 (±0.14) (P < 0.001). The infusion of APC attenuates the inflammatory response during systemic hypoxia at the microvascular level, as evidenced by measurements of leukocyte adherence, emigration, and venular permeability. Further investigation is needed to examine the potential role of APC in the treatment of hypoxic injury.

Original languageEnglish (US)
Pages (from-to)384-387
Number of pages4
Issue number3
StatePublished - Mar 2008


  • Endothelium
  • Hypoxic injury
  • Intravital microscopy
  • Leukocyte adherence
  • Xigris

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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