Can Angiotensin Converting Enzyme Inhibitors Prevent Postoperative Adhesions? Nurullah Bulbuller, M.D.,* ,1 Yavuz Selim Ilhan, M.D.,* Cüneyt Kirkil, M.D.,* Mustafa Cetiner, M.D.,† Özkan Gogebakan, M.D.,* Necip Ilhan, M.D.‡ *Medical Faculty of Fırat University, Department of General Surgery, Elazıg ˘, Turkey; †General Surgery Department, SSK Elazıg ˘ Hospital, Elazıg ˘, Turkey; and ‡Medical Faculty of Fırat University, Department of Biochemistry, Elazıg ˘, Turkey Submitted for publication September 17, 2004 Background. Peritoneal adhesions are pathological fibrotic bands developing after mesothelial damage. Transforming growth factor beta-1 (TGF-1) has mito- genic activities for macrophages and fibroblasts. Over- expression of TGF-1 has been implicated in the pathogenesis of several fibrotic disorders. Angiotensin II increases the expression of the TGF-1 in fibro- blasts. The aim of the study was to investigate the effect of angiotensin converting enzyme inhibitor (ACE) on intraperitoneal adhesions. Materials and methods. Thirty male Wistar albino rats were divided into two groups. In the first proce- dure, laparotomy was performed through a 3-cm mid- line incision. Ileum was divided above 10 cm from ileocecal valve and a single-layer ileoileal anastomosis was performed. Although no treatment was given to rats in group 1, lisinopril (an ACE inhibitor) was given to rats in group 2 for postoperative 7 days in drinking water. Estimated amount of supplied lisinopril was 6.5 mg/kg/day. On postoperative 8th day, relaparotomy was performed and adhesions were evaluated. At the same time, blood samples were taken for TGF-1 measurements. Results. Adhesion severity was significantly less in the ACE inhibitor group (P < 0.001). While mean TGF-1 level was 860.3  108.1 pg/dl (mean  SD) in control group, it was 335.8  52.4 pg/dl in ACE inhibi- tor group (P < 0.001). There was a significant correla- tion between serum TGF-1 levels and grade of adhe- sions (r  0.948). Conclusion. It was concluded that ACE inhibitors might be useful for preventing peritoneal adhesions. © 2005 Elsevier Inc. All rights reserved. Key Words: intraperioneal adhesion; angiotensin converting enzyme inhibitor; lisinopril; transforming growth factor. INTRODUCTION Peritoneal adhesions are defined as pathological fi- brotic bands developed between any surfaces in the peritoneal cavity. For the development of adhesions between two surfaces inside the peritoneum, there must be peritoneal mesothelial damage on at least one surface [1]. Despite recent advances in adhesion pre- vention, the pathogenesis of adhesion formation is still not well understood [2]. A few hours after the mesothe- lial damage, fibrinous exudate is released. When the exudate is absorbed, fibrous bands and newly formed capillary vessels remain at the site and structures form the permanent fibrotic adhesions [1, 3]. Transforming growth factor beta-1 (TGF-1), a polypeptide cytokine with potent chemoattractant and mitogenic activities for macrophages and fibroblasts, is capable of stimulating the expression of various extra- cellular matrix components by fibroblasts. The over- expression of TGF-1 has been implicated in the patho- genesis of several fibrotic disorders at various sites throughout the body such as pulmoner fibrosis, glomer- ulonephritis, cirrhosiss of liver, and skin scarring, as well as peritoneal adhesion formation [4–8]. A variety of physiological roles of angiotensin II (AT-II) have been clarified not only in the pathogenesis and main- tenance of high-blood pressure [9] but also in the stim- ulation of fibroblast proliferation and collagen synthe- sis by non-paranchymal cells [10 –12]. AT-II increases the expression of the TGF-1 and collagen I genes in lung fibroblasts and stimulates the proliferation of mesengial cell [10, 13]. It was shown that an 1 To whom correspondence and reprint requests should be ad- dressed at Fırat U ¨ niversitesi Fırat Tıp Merkezi, Genel Cerrahi A.D., 23200 Elazıg ˘ , Turkey. E-mail: nbulbuller@yahoo.com. Journal of Surgical Research 125, 94 –97 (2005) doi:10.1016/j.jss.2004.11.030 94 0022-4804/05 $30.00 © 2005 Elsevier Inc. All rights reserved.