Attenuating effects of chymase inhibitor on pericardial adhesion following cardiac surgery.
OBJECTIVE
Chymase, a serine protease, is released from mast cells, which is closely associated with adhesion formation. Chymase activates transforming growth factor-beta1 (TGF-beta1), which promotes tissue fibrosis. Recently we have found that chymase may play an important role in adhesion formation in hamsters. Accordingly, this study was designed to confirm that a chymase inhibitor prevents postoperative cardiac adhesions in large animals.


METHODS
In 14 dogs, the epicardium was abraded 200 times with gauze and the mid-portion of the left anterior descending coronary artery (LAD) was exposed with No. 15 blade. Either chymase inhibitor (CI group, n = 7) or placebo (P group, n = 7) was sprayed into the pericardial cavity, then the pericardium was closed. Cardiac chymase activity, the level of TGF-beta1 in the pericardial fluid, the density of epicardial mast cells, the adhesion area between the heart and the pericardium, and the presence of adhesion between the mid-LAD and the pericardium were evaluated 1 and 2 months after surgery. Five nonsurgical dogs were used as a control for cardiac chymase activity.


RESULTS
Cardiac chymase activity and TGF-beta1 level were lower in CI group than in P group (53.7 +/- 35.0 vs. 93.4 +/- 20.4 microU/mg protein, p = 0.01, 3.2 +/- 0.9 vs. 4.3 +/- 1.1 microg/mL, p = 0.06, respectively). In CI group, the density of mast cells (19 +/- 5 vs. 32 +/- 8 cells/cm, p < 0.01), the adhesion area (2.2 +/- 0.8 vs. 7.5 +/- 1.5 cm2, p < 0.01), and adhesions between the heart and the mid-LAD (0% vs. 57%) were all reduced.


CONCLUSIONS
Chymase inhibitor suppresses cardiac chymase activity and reduces the TGF-beta1 level, resulting in a reduction of cardiac adhesion in a large animal.
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yoshiharu
Y
Soga
Shinji
S
Takai
Tadaaki
T
Koyama
Yukiko
Y
Okamoto
Tadashi
T
Ikeda
Kazunobu
K
Nishimura
Mizuo
M
Miyazaki
Masashi
M
Komeda
D000818:Animals; D002452:Cell Count; D053818:Chymases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003331:Coronary Vessels / Q000473:pathology / Q000601:surgery*; D004285:Dogs; D008407:Mast Cells / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D010496:Pericardium / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D009842:Oligopeptides; D053773:Transforming Growth Factor beta1; C102024:succinyl-valyl-prolyl-phenylalanyl-diphenylphosphonate; D053818:Chymases