Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions.
BACKGROUND
Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions.


METHODS
Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. 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. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system.


RESULTS
The severity score was lower in the KGF group than in the control group (11.5 vs 17, p=0.005). The dissection time was lower in the KGF group (9.2+/-1.4 min vs 33.9+/-9.2 min, p=0.004) and presented a significant correlation with the severity score (r=0.83, p=0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly lower in the KGF group than in the control group.


CONCLUSIONS
The stimulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies.
Lopes
Jackson B
JB
Division of Cardiothoracic Surgery, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
Dallan
Luis A O
LA
Campana-Filho
Sérgio P
SP
Lisboa
Luiz A F
LA
Gutierrez
Paulo S
PS
Moreira
Luiz Felipe P
LF
Oliveira
Sergio A
SA
Stolf
Noedir A G
NA
D000818:Animals; D004195:Disease Models, Animal; D004210:Dissection; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects; D051523:Fibroblast Growth Factor 7 / Q000627:therapeutic use*; D006331:Heart Diseases / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D008297:Male; D010496:Pericardium / Q000473:pathology / Q000601:surgery*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012086:Reoperation; D034421:Sus scrofa; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control / Q000601:surgery
C496453:FGF7 protein, human; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7