Activated Protein C Attenuates Microvascular Injury During Systemic Hypoxia (original) (raw)

Shock, 2007

Abstract

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-microm venule), leukocyte emigration (no. per 4,000 microm(2)), 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-microm venule in hypoxic rats to 4.4 (+/-1.5) cells/100-microm 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-microm(2) venule, but was reduced to 3.5 (+/-0.3) cells/4,000-microm(2) 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…

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