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Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions

^a Division of Cardiothoracic Surgery, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
^b Department of Physico-chemistry, Institute of Chemistry at São Carlos, University of São Paulo, Brazil
^c Laboratory of Pathology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil

Received 9 May 2008; received in revised form 4 September 2008; accepted 29 September 2008.

^_* Corresponding author. Address: Hospital Márcio Cunha (Centro de Estudos), Avenida Engenheiro Kiyoshi Tsunawaki, s/n – Ipatinga/MG, 35160-158, Brazil. Tel.: +55 31 8827 0465; fax: +55 31 3829 9433. (Email: jackson.lopes{at}incor.usp.br).

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. Conclusion: 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.

Key Words: Adhesions/prevention and control • Animals • Random allocation • Pericardium • Swine • Fibroblast growth factor 7 (keratinocyte growth factor)