Main Article Content
Background/Aim: To investigate the effect of specific phosphodiesterase 5 inhibitor on anastomotic healing in rat small intestine which was an ischemia reperfusion injury.
Materials and Methods: 48 male Sprague-Dawley rats divided into four equal groups (n = 12). Standardized transection, a full cut was made approximately 15 centimeters proximal to the cecum and anastomosis were performed to the tips of bowel. Group 1, normal anastomosis; group 2, normal anastomosis + tadalafil treatment; group 3, intestinal anastomosis was performed after 30 minutes of intestinal ischemia and reperfusion; group 4, intestinal anastomosis was performed after 30 minutes of intestinal ischemia and reperfusion + tadalafil treatment. Postoperative 4th day anastomosis bursting pressure, tissue hydroxyproline level, and histopathologically anastamosis evaluation were assessed by modified Ehrlich-Hunt scoring.
Results: The use of Tadalafil in ischemia and reperfusion groups was found to significantly increase the burst pressures. There was a statistically significant difference in hydroxyproline concentration between all groups. There was no statistically significant difference between the groups in histological evaluation in terms of inflammatory cell infiltration, vascular reaction and anastomotic collagen deposition.
Conclusion: Although tadalafil cannot be shown histopathologically, it was concluded that it has positive effects on recovery of small intestine anastomosis after reperfusion of intestinal ischemia.
Kuzu MA, Aslar AK, Mahmoud H, et al. Factors affecting the clinical outcome of primary resection for malignant colonic obstruction: Multivariate analysis. Colorectal Disease. 2003;5:91-91.
Nesbakken A, Nygaard K, Lunde OC, Blucher J, Gjertsen O, et al. Anastomotic leak following mesorectal excision for rectal cancer: True incidence and diagnostic challenges. Colorectal Dis. 2005;7(6):576–581. DOI: 10.1111/j.1463-1318.2005.00870.x
McDermott FD, Heeney A, Kelly ME, Steele RJ, et al. Systematic review of postoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg. 2015;102(5): 462-479. DOI: 10.1002/bjs.9697
Kuzu MA, Köksoy C, Kale IT, Tanik A, Terzi C, Elhan AH. Reperfusion injury delays healing of intestinal anastomosis in a rat. Am J of Surgery. 1998;176:348-351.
Kaya Y, Coskun T, Ayhan S, Kara E, Sakarya A, et al. The effect of Tadalafil on anastomotic healing in iscemic small intestine in rats. Surg Today. 2010;(40): 555-560. DOI:10.10007/s00595-010-4229-9
Megison SM, Horton JW, Chao H, Walker PB. A new model for intestinal ischemia in the rat. J Surg Res. 1990;49:168-173. DOI: 10.1016/0022-4804(90)90257-3
Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng PW, et al. Cerrent mechanistic consepts in ischemia and reperfusion injury. Cell Physiol Biochem. 2018;46(4): 1650-1667. DOI: 10.1159/000489241
Saidi RF, Kenari SK. Liver ischemia/reperfusion injury: An overview. J Invest Surg. 2014;27(6):366-379. DOI: 10.3109/08941939.2014.932473
Gonzalez LM, Moeser AJ, Blikslager AT. Animal models of ischemia-reperfusion-induced intestinal injury: Preogress and promise for translational research. Am J Pkysiol Gastrointerest Liver Physiol. 2015; 308(2):63-75. DOI: 10.1152/ajpgi.0012.2013
Grace PA. Ischaemia-reperfusion injury. British J of Surgery. 1994;81:637-647. DOI: 10.1002/bjs.1800810504
Zimmerman BJ, Granger DN. Reperfusion injury. Surgical Clinics of North America. 1992;72:65-83. DOI: 10.1016/s0039-6109(16)45628-8
Lefer AM., Lefer DJ. Pharmacology of the endothelium in ischemia reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol. 1993;33:71-90. DOI: 10.1146/annurev.pa.33.040193.000443
Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: Results of integrated analyses. J Urol. 2002;168:1332–6. DOI: 10.1097/01.ju.0000028041.27703.da
Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119:2894–903. DOI: 10.1161/CIRCULATIONAHA.108.839274
Gudmundsdottir IJ, McRobbie SJ, Robinson SD, Newby DE, Megson IL. Sildenafil potentiates nitric oxide mediated inhibition of human platelet aggregation. Biochemical and Biophysical Research Communications. 2005;337:382-385. DOI: 10.07/s00384-002-0392-9
Colle I, De Vriese, Van Vlierberghe H, Lameire NH, De Vos M. Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients. Liver International. 2004;24:63-68. DOI: 10.1111/j.1478-3231.2004.00892.x
Sharma R. Novel phosphodiesterase-5 inhibitors: Current indications and future directions. Indian J Med Sci. 2007;61(12): 667-79. DOI: 10.4103/0019-5359.37789
Mansson P, Zhang XW, Jeppsson B, Thorlacius H. Anastomotic healing in the rat colon: Comparison between a radiological method, breaking strength and bursting pressure. Int J Colorectal Dis. 2002;17:420-425. DOI: 10.1007/s00384-002-0392-9
Akyuz C, Yasar NF, Uzun O, Peker KD, Sunamak O, et al. Effect of melatonin on colonic anastomosis healing following chemotherapy in rats. Singapore Med J. 2018;59(10):545-549. DOI: 10.11622/smedj.2018035
Bergman I, Loxley R. Two Improved and simplifed methods for spectrophotometric determination of hydroxyprolin. Anal. Chem. 1964;35:1961-1964.
Ehrlich HP, Tarver H, Hunt TK. Effects of vitamin A and glucocorticoids upon inflamation and collagen synthesis. Ann Surg. 1973;177:222-7. DOI: 10.1097/00000658-197302000-00017
Ayten R, Çetinkaya Z, Girgin M, Özercan İ, Üstündağ B, et al. The effects of intraperitoneal sildenafil administration on healing of left colonic anastomoses and intraabdominal adhesion formation in the presence of intraabdominal infection. Dis Colon Rectum. 2008;51(12): 1837-41. DOI: 10.1007/s10350-008-9398-x
Li Z, Xi X, Gu M, et al. A Stimulatory role for cGMP-dependent rotein kinase in platalet activation. Cell. 2003;112:77-86. DOI: 10.1016/s0092-8674(02)01254-0
Bischoff E. Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Int J Import Res. 2004;16:11-14. DOİ: 10.1038/sj.ijir.3901208
du Toit EF, Rossouw E, Salie R, Opie LH, Lochner A. Effect of sildenafil on reperfusion function, infarct size, and cyclic nucleotide levels in the isolated rat heart model. Cardiovasc Drugs Ther. 2005;19:23-31. DOİ: 10.1007/s10557-005-6894-2
Zhang L, Zhang RL, Wang Y, Zhang C, Zhang ZG, et al. Functional recovery in aged and young rats after embolic stroke: Treatment with a phosphodiesterase type 5 inhibitor. Stroke. 2005;36:847-52. DOI: 10.1161/01.STR.0000158923.19956.73
Posma LAE, Bleichrodt RP, van Goor H, Hendriks T. Ischemia and prolonged reperfusion before anastomotic construction do not reduce wound strength in the rat intestine. Surgery. 2006;139:671-7. DOI: 10.1016/j.surg.2005.10.014
Hasanoğlu A, Erkan S, Temel S, Urhan MK, Güler O. Effect of sildenafıl citrate on healing of colonic anastomoses. Turkish Medical Journal. 2007;1:66-75.
Uzun H, Konukoğlu D, Nuri MK, Ersoy EY, Özçevik S, et al. The effects of sildenafil citrate on Ischemic colonic anastomotic healing in rats: Its relationship between nitric oxide and oxidative stres. World J Surg. 2008;32:2107-2113. DOI: 10.1007/s00268-008-9661-2
Attard JA, Raval MJ, Martin GR, et al. The effects of systemic hypoxia on colon anastomotic healing: An animal model. Dis Colon Rectum. 2005;48:1460-1470. DOI: 10.1007/s10350-005-0047-3