Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model.
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 beta1, 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 beta1 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 beta1 were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (45.8 +/- 18.7 vs 79.7 +/- 13.7 microU/mg protein [P <.025] and 15.6 +/- 6.5 vs 33.2 +/- 9.8 microg/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).


CONCLUSIONS
Use of a chymase inhibitor suppresses not only cardiac chymase activity but also the level of transforming growth factor beta1, and this results in a reduction in postoperative cardiac adhesion.
Soga
Yoshiharu
Y
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Japan.
Takai
Shinji
S
Koyama
Tadaaki
T
Okamoto
Yukiko
Y
Ikeda
Tadashi
T
Nishimura
Kazunobu
K
Miyazaki
Mizuo
M
Komeda
Masashi
M
D000818:Animals; D001707:Biopsy, Needle; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods; D053818:Chymases; D006224:Cricetinae; D004195:Disease Models, Animal; D006331:Heart Diseases / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D000267:Tissue Adhesions / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000187:drug effects*
D015842:Serine Proteinase Inhibitors; D016212:Transforming Growth Factor beta; D012697:Serine Endopeptidases; D053818:Chymases