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J Thorac Cardiovasc Surg 2004;127:72-78
© 2004 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

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

^a Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
^b Department of Pharmacology, Osaka Medical College, Takatsuki city, Osaka, Japan

Received for publication September 19, 2002; revisions received November 12, 2002; accepted for publication January 14, 2003.

^* Address for reprints: Masashi Komeda, MD, PhD, Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, Japan 606-8507
masakom{at}kuhp.kyoto-u.ac.jp

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 ß1, 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 ß1 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 ß1 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 ß1, and this results in a reduction in postoperative cardiac adhesion.

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