Cüneyt KIRKILa, Serdar COŞKUN, Nurullah BÜLBÜLLER, Erhan AYGEN, KORAY KARABULUT

Lisinopril,sildenafil ve birliktekullanımlarının karıniçi yapışıklık oluşmasınıönleyici etkileri

Amaç: Bu çalışmada lisinopril ve sildenafilin karın içi yapışıklıkları önlemedeki etkinliklerinin karşılaştırılması ve birlikte uygulanmaları halinde sinerjik etki gösterip göstermeyeceklerinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Kırk adet rat 4 gruba ayrılıp mezotel hasarı oluşturuldu. Birinci gruptaki ratlara her hangi bir ilaç verilmez iken 2. gruptakilere lisinopril (6.5 mg/kg/gün), 3. gruptakilere sildenafil (0.8 mg/kg/gün) ve 4. gruptakilere hem lisinopril hem de sildenafil gavaj yoluyla 7 gün verildi. Sonra karın boşluğu tekrar açılıp yapışıklık skorları belirlendi. Bulgular: Grupların ortalama karın içi yapışıklık skorları sırasıyla 2.3±0.5, 0.9±0.7, 0.6±0.8 ve 0.7±0.9 idi. Tüm tedavi gruplarının yapışıklık skorları kontrol grubununkinden belirgin olarak daha düşüktü (p0.05, grup 3 vs grup 4 p>0.5). Sonuç: Lisinopril ve sildenafil tek başlarına karın içi yapışıklık gelişmesini önlemede etkilidir. Birlikte kullanımları onların güçlerini artırmaz.

The preventing effects of lisinopril, sildenafil and combined usage of them on the formation of intra-abdominal adhesion

Objective: In this study, it was aimed to compare the effectiveness of lisinopril and sildenafil on the prevention of intraabdominal adhesions and to investigate whether there was a synergistic effect if they were combined. Materials and Methods: Fourty rats divided into four groups and mesothelial damage created. No medication was given to rats in group 1, lisinopril (6.5 mg/kg/d) in group 2, sildenafil (0.8 mg/kg/d) in group 3, and lisinopril combined with sildenafil in group 4 were given to rats by gavage for 7 days. Then, abdominal cavities were re-opened and adhesion scores were determined. Results: The mean intra-abdominal adhesion scores of groups were 2.3±0.5, 0.9±0.7, 0.6±0.8, and 0.7±0.9, respectively. The mean adhesion scores of all treatment groups were significantly lower than control group (p<0.001). Whereas, there were no statistically differences between treatment groups (group 2 vs group 4 p>0.05,and group 3 vs group 4 p>0.5). Conclusion: : Lisinopril and sildenafil alone is effective in preventing the formation of intra-abdominal adhesions. Their combination does not incre- ase their potencies.

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1.Hellebrekers B, Trimbos-Kemper T, Trimbos J, Emeis J, Kooistra T. Use of fibrinolytic agents in the prevention of post-operative adhesion formation. Fertil Steril 2000; 74: 203- 212.
2.Nair S, Bhat I, Aurora A. Role of proteolytic enzyme in the prevention of post-operative intraperitoneal adhesions. Arch Surg 1974; 108: 849-853.
3.Kıkırdak T, Uysal E, Korun N. Karın içi yapışıklıkların ön- lenmesinde metilprednizolonun farklı dozlarının etkinliğinin incelenmesi. Ulus Travma Acil Cerrahi Derg 2008; 14: 188- 191.
4.Lauder CIW, Garcea G, Strickland A, Maddern GJ. Abdomi- nal adhesion prevention: Stil a sticky subject? Dig Surg 2010; 27: 347- 358.
5.Bulbuller N, Ilhan YS, Kirkil C, Cetiner M, Gogebakan O, Ilhan N. Can angiotensin converting enzyme inhibitors prevent postoperativ adhesions? J Surg Res 2005; 125: 94-97.
6.Batukan C, Ozgun MT, Basbug M, Muderris II. Sidenafil reduces postoperative adhesion formation in a rat uterine horn model. Eur J Obstet Gynecol Reprod Biol 2007; 135: 183-187.
7.Mollnau H, Wendt M, Szocs K et al. Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 2002; 90: 58–65.
8.Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, Beavo JA. Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem 2002; 277: 3310–3317.
9.Krause TJ, Zazanis GA, McKinnon RD. Prevention of posto- perative adhesions with the chitin derivate N-O- carboxymethylchitosan. Wound Repair Regen 1996; 4: 53-57.
10.Morgan HE, Baker KM. Cardiacneural, and endocrine dependence.25. hypertrophy. Mechanical, Circulation 1991; 83: 13-
11.Wolf G, Haberstroh U, Neilson EG. Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesengial cells. Am J Pathol 1992; 140: 95-107.
12.Brilla CG, Maisch B, Weber KT. Renin-angiotensin system and myocardial collagen matrix remodeling in hypertansive heart disease. In vivo and in vitro studies on collagen matrix regulation. Coin Invest 1993; 71: 35-41.
13.Weber KT, Sun Y, Tyagi SC, Clentjens JP. Collagen network of the myocardium: function, structural remodeling and regu- latory mechanisms. J Mol Cell Cardiol 1994; 26: 279-292.
14.Marshall RP, McAnulty RJ, Laurent GJ. Angiotensin II is mitogenic for human lung fibroblasts via activation of the type I receptor. Am J Respir Crit Care Med 2000; 161: 1999-2004.
15.Mezzano SA, Ruiz-Ortega M, Egido J. Angiotensinrenal fibrosis. Hypertension 2001; 38: 635-638. II and
16.Kagami S, Border WA, Miller DE, Noble NA. Angiotensin II stimulates extracellular matrix protein synthesis through in- duction of transforming growth factor-β expression in rat glo- merular mesengial cells. J Clin Invest 1994; 93: 2431-2437.
17.Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med 1994; 331: 1286-1292.
18.Roberts AR. Transforming growth factor-b: Activity and efficacy in animal models of wound healing. Wound Repair Regeneration 1995; 3: 408-418.
19.Williams RS, Rossi AM, Chegini N, Schultz G. Effect of transforming growth factor β on postoperative adhesion for- mation and intact peritoneum. J Surg Res 1992; 52: 65-70.
20.Chegini N. The role of growth factors in peritoneal healing: Transforming growth factor beta (TGF-beta). Eur J Surg 1997; 577: 17-23.
21.Lucas PA, Warejcka DJ, Young HE, Lee BY. Formation of abdominal adhesions is inhibited by antibodies to transforming growth factor-β1. J Surg Res 1996; 65: 135-138.
22.Zhang H, Pakeerappa P, Lee HJ, Fisher SA. Induction of PDE5 and de-sensitization to endogenous NO signaling in a systemic resistance artery under altered blood flow. J Mol Cell Cardiol 2009; 47: 57-65.
23.Colle I, De Vriese, Van Vlierberghe H, Lamerie NH, De Vos M. Systemic and splanchnic haemodynamic effects of sildena- fil in an in vivo animal model of cirrhosis support for a risk in cirrotic patients. Liver Int 2004; 24: 63-68.
24.Sirotkin AV, Makarevich AV, Pivko J, Kotwica J, Genieser H, Bulla J. Effect of cGMP analogues and protein kinase G bloc- ker on secretory activity, apoptosis and the cAMP/protein ki- nase A system in porcine ovarian granulosa cells in vitro. J Steroid Biochem Mol Biol 2000; 74: 1–9.
25.Redondo J, Bishop JE,Wilkins MR. Effect of atrial natriuretic peptide and cyclic GMP phosphodiesterase inhibition on col- lagen synthesis by adult cardiac fibroblasts. Br J Pharmacol 1998; 124: 1455–1462.
26.Ayten R, Cetinkaya Z, Girgin M,Ozercan I, Ustundag B, Aygen E. The effects of intraperitoneal sildenafil administra- tion 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.
27.Joannides R, Bizet-Nafeh C, Costentin A et al. Chronic ACE inhibition enhances the endothelial control of arterial mecha- nics and flow-dependent vasodilatation in heart failure. Hyper- tension 2001; 38: 1446–1450.
28.Katz SD, Balidemaj K, Homma S,Wu H, Wang J, Maybaum S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000; 36: 845–851.
29.Hryniewicz K, Dimayuga C, Hudaihed A, et al. Inhibition of angiotesin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure. Clin Sci 2005; 108: 331-338.