Synergism between keratinocyte growth factor and carboxymethyl chitosan reduces pericardial adhesions.
BACKGROUND
Mesothelial injury is the pivot in the development of adhesions. An increase in the proliferation of mesothelial cells was verified by in vitro studies with the use of keratinocyte growth factor (KGF). This study investigated the influence of KGF associated with thermo-sterilized carboxymethyl chitosan (NOCCts) in the reduction of pericardial adhesions.


METHODS
An induction model of pericardial adhesion was carried out in 24 pigs. Animals were randomly allocated to receive topical application of KGF, KGF + NOCCts, NOCCts, or saline (control). At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histologic sections were stained with sirius red for a morphometric evaluation using a computer-assisted image analysis system. Cytokeratin AE1/AE3 immunostaining were employed to identify mesothelial cells.


RESULTS
The severity score expressed in median (minimum to maximum), in relation to the control group (17 [15 to 18]), was lower in the KGF + NOCCts group (7 [6 to 9], p < 0.01) followed by the KGF group (11.5 [9 to 12], 0.01 < p < 0.05) and the NOCCts group (12 [9 to 14], p > 0.05). The dissection time was significantly lower in the KGF + NOCCts group (7.1 + or - 0.6 vs 33.9 + or - 9.2 minutes, p < 0.001). A significantly less sharp dissection was also required in the KGF + NOCCts group. In the adhesion segment, a decreased collagen proportion was found in the KGF + NOCCts group (p < 0.05). Mesothelial cells were present more extensively in groups in which KGF was delivered (p = 0.01).


CONCLUSIONS
The use of KGF associated with NOCCts resulted in a synergic action that decreases postoperative pericardial adhesions in a highly significant way.
Lopes
Jackson B
JB
Division of Cardiothoracic Surgery, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. jackson.lopes@incor.usp.br
Dallan
Luis Alberto O
LA
Moreira
Luiz Felipe P
LF
Campana Filho
Sérgio P
SP
Gutierrez
Paulo S
PS
Lisboa
Luiz Augusto F
LA
de Oliveira
Sergio Almeida
SA
Stolf
Noedir Antonio G
NA
D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004357:Drug Synergism; D051523:Fibroblast Growth Factor 7 / Q000627:therapeutic use*; D006331:Heart Diseases / Q000517:prevention & control*; D008297:Male; D010496:Pericardium; D013552:Swine; D000267:Tissue Adhesions / Q000517:prevention & control
C514968:carboxymethyl-chitosan; D051523:Fibroblast Growth Factor 7; D048271:Chitosan