Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model

Abstract

Objective Chymase is one of the inflammatory mediators and is released from mast cells, which are closely associated with adhesion formation. Chymase also activates transforming growth factor β1, which promotes tissue fibrosis. However, the role of chymase in cardiac adhesion formation has not yet been elucidated. We have assessed whether a specific chymase inhibitor, Suc-Val-Pro-Phe p (OPh) 2, prevents postoperative cardiac adhesions in hamsters. Methods In 66 hamsters the epicardium was abraded, and then either chymase inhibitor or placebo was injected into the left thoracic cavity, leaving the pericardium open. Cardiac chymase activity, the level of transforming growth factor β1 in the pleural fluid, and the density of epicardial mast cells were measured 3 days postoperatively. The degree of adhesion formation was evaluated macroscopically and histologically 2 weeks postoperatively by using a grading score ranging from 0 (no adhesions) to 4 (severe adhesions). Results The cardiac chymase activity and level of transforming growth factor β1 were lower in the chymase inhibitor–treated group compared with in the placebo-treated group (45.8 ± 18.7 vs 79.7 ± 13.7 μU/mg protein [ P < .025] and 15.6 ± 6.5 vs 33.2 ± 9.8 μg/mL [ P < .01], respectively). The density of mast cells was higher in the placebo-treated group, and there was suppression to 60% of this value in the chymase inhibitor–treated group. The adhesion scores were lower in the chymase inhibitor–treated group compared with in the placebo-treated group (1.3 ± 1.3 vs 3.0 ± 1.1, P < .01). Conclusion Use of a chymase inhibitor suppresses not only cardiac chymase activity but also the level of transforming growth factor β1, and this results in a reduction in postoperative cardiac adhesion.