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The effect of tadalafil on anastomotic healing in ischemic small intestine in rats

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Abstract

Purpose

To investigate the effect of tadalafil on anastomotic healing in an ischemic small intestine.

Methods

Standardized transection and anastomosis in the small intestine were performed in 48 male Sprague-Dawley rats divided into four equal groups (n = 12): group 1, normal anastomosis; group 2, ischemic anastomosis; group 3, normal anastomosis+tadalafil treatment; group 4, ischemic anastomosis+tadalafil treatment. Ischemia was established by ligating 2 cm of mesentery on either side of the anastomosis. Tadalafil was given to the rats once a day at dose of 5 mg/kg. The anastomotic bursting pressures and hydroxyproline concentrations were measured on postoperative day 4. A histopathological evaluation of the anastomoses was also performed.

Results

The bursting pressure and hydroxyproline concentration in group 2 were significantly lower than those in the other groups. There was no difference in the hydroxyproline concentration among groups 1, 3, and 4. While there was no difference between groups 3 and 4, the bursting pressures were significantly higher in groups 3 and 4 than in group 1. The histopathological evaluation revealed no significant differences in inflammatory cell infiltration, vascularization, or anastomotic collagen deposition among the groups.

Conclusion

Tadalafil treatment improved the anastomotic bursting pressure and the hydroxyproline concentration in both normal and ischemic small intestine anastomosis.

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References

  1. Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V, et al. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002;168:1332–1336.

    Article  CAS  PubMed  Google Scholar 

  2. Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009;119:2894–2903.

    Article  CAS  PubMed  Google Scholar 

  3. Li Z, Xi X, Gu M, Feil R, Ye RD, Eigenthaler M, et al. A Stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell 2003;112:77–86.

    Article  CAS  PubMed  Google Scholar 

  4. Bischoff E. Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Int J Impot Res 2004;16(suppl 1):11–14.

    Article  Google Scholar 

  5. Rao YJ, Xi L. Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts. Acta Pharmacol Sin 2009;30:1–24.

    Article  CAS  PubMed  Google Scholar 

  6. Tsai BM, Turrentine MW, Sheridan BC, Wang M, Fiore AC, Brown JW, et al. Differential effects of phosphodiesterase-5 inhibitors on hypoxic pulmonary vasoconstriction and pulmonary artery cytokine expression. Ann Thorac Surg 2006;81:272–278.

    Article  PubMed  Google Scholar 

  7. Ko IG, Shin MS, Kim BK, Kim SE, Sung YH, Kim TS, et al. Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis in hippocampal neuronal cells in gerbils. Pharmacol Biochem Behav 2009;91:629–635.

    Article  CAS  PubMed  Google Scholar 

  8. Oh M, Chang H, Minn KW. The effects of tadalafil on axial-pattern skin flap survival in rats. Dermatol Surg 2008;34:626–630.

    Article  CAS  PubMed  Google Scholar 

  9. Foster ME, Brennan SS, Morgan A, Leaper DJ. Colonic ischemia and anastomotic healing. Eur Surg Res 1985;17:133–139.

    Article  CAS  PubMed  Google Scholar 

  10. Garcia JG, Criado FJ, Persona MA, Alonso AG. Healing of colonic ischemic anastomoses in the rat. Dis Colon Rectum 1998;41:892–895.

    Article  CAS  PubMed  Google Scholar 

  11. Griffen TS, Hagihara PF. Ischemic colitis in rats. Dis Colon Rectum 1982;25:638–640.

    Article  CAS  PubMed  Google Scholar 

  12. Woessner JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961;93:440–447.

    Article  CAS  PubMed  Google Scholar 

  13. Ehrlich HP, Tarver H, Hunt TK. Effects of vitamin A and glucocorticoids upon inflammation and collagen synthesis. Ann Surg 1973;177:222–227.

    Article  CAS  PubMed  Google Scholar 

  14. Dawson-Saunders B, Trapp R (editors). Basic and clinical biostatistics. Norwalk: Appleton Lange; 1998. p. 133–139.

    Google Scholar 

  15. Hendriks T, Mastboom WJ. Healing of experimental intestinal anastomoses. Parameters for repair. Dis Colon Rectum 1990;33:891–901.

    Article  CAS  PubMed  Google Scholar 

  16. Koruda MJ, Rolandelli RH. Experimental studies on the healing of colonic anastomoses. J Surg Res 1990;48:504–515.

    Article  CAS  PubMed  Google Scholar 

  17. Hogstrom H, Haglund U. Postoperative decrease in suture holding capacity in laparotomy wounds and anastomoses. Acta Chir Scand 1985;151:533–535.

    CAS  PubMed  Google Scholar 

  18. Jiborn H, Ahonen J, Zederfeldt B. Healing of experimental colonic anastomoses. I. Bursting strength of the colon after left colon resection and anastomosis. Am J Surg 1978;136:587–594.

    Article  CAS  PubMed  Google Scholar 

  19. Hamzaoglu I, Karahasanoglu T, Aydın S, Sahin DA, Carkman S, Sarıyar M, et al. The effect of hyperbaric oxygen on normal and ischemic colon anastomoses. Am J Surg 1998;176:458–461.

    Article  CAS  PubMed  Google Scholar 

  20. Dinc S, Gulcelik MA, Kuru B, Ergeneci D, Camlibel M, Caydere M, et al. Effects of locally applied recombinant human granulocyte-macrophage colony-stimulating factor on ischemic bowel anastomoses in rat. Eur Surg Res 2004;36:59–63.

    Article  CAS  PubMed  Google Scholar 

  21. Wright PJ. Comparison of phosphodiesterase type 5 (PDE5) inhibitors. Int J Clin Pract 2006;60:967–975.

    Article  CAS  PubMed  Google Scholar 

  22. Kloner RA. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. Circulation 2004;110:3149–3155.

    Article  PubMed  Google Scholar 

  23. Sawamura F, Kato M, Fujita K, Nakazawa T, Beardsworth A. Tadalafil, a long-acting inhibitor of pde5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats. J Pharmacol Sci 2009;111:235–243.

    Article  CAS  PubMed  Google Scholar 

  24. Hunt TK, Twomey P, Zederfeldt B, Dunphy JE. Respiratory gas tensions and pH in healing wound. Am J Surg 1967;114:302–307.

    Article  CAS  PubMed  Google Scholar 

  25. Norlen K, Rentzhog L, Wikstrom S. Hemodynamic effects of phenoxybenzamine and volume replacement in segmental ischemia of the rat small intestine. Acta Chir Scand 1978;144:307–312.

    CAS  PubMed  Google Scholar 

  26. Norlen K, Rentzhog L, Wikstrom S. The effect of dopamine in segmental ischemia of the small intestine in the rat. Acta Chir Scand 1978;144:313–320.

    CAS  PubMed  Google Scholar 

  27. Dias-Junior CA, Cau SB, Oliveira AM, Castro MM, Montenegro MF, Gerlach RF, et al. Nitrit or sildenafil, but not BAY 41-2272, blunt acute pulmonary embolism-induced increases in circulating matrix metalloproteinase-9 and oxidative stress. Thromb Res 2009;124:349–355.

    Article  CAS  PubMed  Google Scholar 

  28. Uzun H, Konukoglu D, Nuri MK, Ersoy EY, Ozçelik S, Yavuz N, et al. The effects of sildenafil citrate on ischemic colonic anastomotic healing in rats: its relationship between nitric oxide and oxidative stress. World J Surg 2008;32:2107–2113.

    Article  PubMed  Google Scholar 

  29. Ayten R, Cetinkaya Z, Girgin M, Ozercan I, Ustundag B, Aygen E, et al. The effects of intraperitoneal sildenafil administration on healing of left colonic anastomoses and intra-abdominal adhesion formation in the presence of intra-abdominal infection. Dis Colon Rectum 2008;51:1837–1841.

    Article  PubMed  Google Scholar 

  30. Irkorucu O, Ucan BH, Cakmak GK, Emre AU, Tascilar O, Ofluoglu E, et al. Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: yes, “no”. Int J Surg 2009;7:39–43.

    Article  PubMed  Google Scholar 

  31. Yagci G, Ozturk E, Ozgurtas T, Gorgulu S, Kutlu OC, Topal T, et al. Preoperative and postoperative administration of hyperbaric oxygen improves biochemical and mechanical parameters on ischemic and normal colonic anastomosis. J Invest Surg 2006;19:237–244.

    Article  PubMed  Google Scholar 

  32. Cetinkaya Z, Esen K, Ozercan IH, Ustundag B, Ayten R, Aygen E, et al. The effect of bosentan on healing of colonic anastomosis. World J Emerg Surg 2006;1:37.

    Article  PubMed  Google Scholar 

  33. Kashiwagi H. The lower limit of tissue blood flow for safe colonic anastomosis: An experimental study using laser Doppler velocimetry. Surg Today 1993;23:430–438.

    Article  CAS  PubMed  Google Scholar 

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Kaya, Y., Coskun, T., Ayhan, S. et al. The effect of tadalafil on anastomotic healing in ischemic small intestine in rats. Surg Today 40, 555–560 (2010). https://doi.org/10.1007/s00595-010-4229-9

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  • DOI: https://doi.org/10.1007/s00595-010-4229-9

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