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Updated: Jun 16, 2026
Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program
Published on: February 25, 2015
Effects of activated protein C on ventilator-induced lung injury in rats
Jiunn-Song Jiang1, Hsiu-Chu Chou, Leng-Fang Wang
1Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital and School of Respiratory Therapy, Taipei, Taiwan, ROC.
Background:
Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis.
Objectives:
The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury.
Methods:
Rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP; HVZP) protocol by a volume-cycled ventilator for 2 h at a VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO(2) of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 microg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group.
Results:
Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups.
Conclusions:
These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.
