THE EFFECT OF PROTEASE INHIBITOR ON REPERFUSION INJURY AFTER UNILATERAL PULMONARY ISCHEMIA

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Abstract
Reperfusion injury is a large problem in the early stage after lung transplantation. Its prevention by protease inhibitor was evaluated experimentally. Warm ischemic models were made with the left lungs of adult mongrel dogs. The time for the warm ischemic procedure was set at 2 hr, and the lungs were reperfused for 2 hr. The experimental group was divided into a control group, a UTI (urinary trypsin inhibitor) group and a GM (gabexate mecilate) group. To the UTI group, 10,000 units/kg of UTI was administrated during reperfusion, and to the GM group, 20 mg/kg of gabexate mecilate was administrated similarly. In the control group, the pulmonary vascular resistance and the lung tissue wet and dry weight ratios (W/D ratios) increased significantly, and thickened interstitium and infiltration of neutrophils were observed histologically after reperfusion. In the GM group, W/D ratios increased significantly, and histological appearances were similar to the control group. In the UTI group, the pulmonary vascular resistance increased slightly, but the W/D ratio did not increase significantly, and no changes were seen histologically after reperfusion. In the survival experiment, only two of the five dogs survived for more than seven days in the control and GM groups, while all five dogs survived for more than seven days in the UTI group. These results indicate that UTI significantly attenuates reperfusion injury, perhaps by inhibiting neutrophil proteases.

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