Archives of Gynecology and Obstetrics

, Volume 299, Issue 6, pp 1691–1699 | Cite as

A new approach to prevent ischemia/reperfusion injury in a rat model: remote ischemic conditioning

  • Mehmet SipahiEmail author
  • Mucahit Gunaydin
  • Tugrul Kesicioglu
  • Murat Usta
  • Berna Tezcan Yavuz
  • Canberk Tomruk
Gynecologic Oncology



To evaluate the effect of remote ischemic conditioning (RIC) on ovarian ischemia/reperfusion injury in a rat model.


A total of 36 Wistar albino rats with a body weight of 220–250 g were used for this study. Right adnexal torsion was performed for 180 min, and at the end of the period, the adnex was released and the abdomen was reclosed for 180 min for reperfusion. Torsion and detorsion procedures were applied to all rats except group 1 (sham, control). The right lower extremity was tied to perform remote tissue ischemia in groups 3, 4, 5, and 6. The goal of the procedure, which was purplish discoloration and pulselessness of the extremity, was maintained. After 5 min of ischemia, reperfusion was achieved for 5 min. Repeating this procedure 3 times was defined as hypoxia attacks (RIC). Retrieved ovaries were examined for tissue injury with biochemical, histopathologic, and immunohistochemical analysis.


Unlike the control group, vascular congestion, hemorrhage, edema, and inflammatory cell infiltration were observed in group 2 (only I/R [ischemia/reperfusion]). In groups 3 (I/R + RIC), 4 (I/R + RIC), 5 (I/R + RIC), and 6 (I/R + RIC), edema and inflammatory cell infiltration were not observed. However, vascular congestion and hemorrhage that were detected in these groups were higher than in group 1 (Control) and less than in group 2 (I/R). The Caspase-3 Index was found to be increased in all groups compared to group 1 (P < .001). However, the increase in the RIC-performed groups was significantly less than in group 2. The apoptotic index, which was determined by the TUNEL, was also found to be increased in all groups compared to group 1 (P < .001). When the comparison was made in relation to group 2, the decrease of AI in RIC-performed groups was statistically significant, except the decrease in group 6 (P = .29).


It is not clinically conceivable to prepare the tissue for pre-ischemia in ovarian torsion. However, the RIC application, which will be initiated if torsion is suspected when arrangements are made for surgery, might be a simple, effective, and inexpensive approach to prevent I/R injury in the clinic.


Ischemia Remote ischemia Ovarian torsion Reperfusion injury Rat model 



The authors thank Vehbi Yavuz Tokgoz for coordination at the beginning of the study.

Authors’ contributions

MS: 65%: Hypothesis, development of project, surgery, and statistical analyses. MG: 10%: Surgery. TK: 10%: Surgery. Murat Usta: 5%: Biochemistry. BT: 5%: Histology. CT: 5%: Histology

Funding information

The study was supported by the Giresun University BAP Committee (SAG-BAP-A-160317-87).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    McWilliams GD, Hill MJ, Dietrich CS 3rd (2008) Gynecologic emergencies. Surg Clin North Am 88(2):265–283, vi. CrossRefGoogle Scholar
  2. 2.
    Somuncu S, Cakmak M, Dikmen G, Akman H, Kaya M (2008) Ischemia-reperfusion injury of rabbit ovary and protective effect of trapidil: an experimental study. Pediatr Surg Int 24(3):315–318. CrossRefGoogle Scholar
  3. 3.
    Hibbard LT (1985) Adnexal torsion. Am J Obstet Gynecol 152(4):456–461CrossRefGoogle Scholar
  4. 4.
    Oelsner G, Cohen SB, Soriano D, Admon D, Mashiach S, Carp H (2003) Minimal surgery for the twisted ischaemic adnexa can preserve ovarian function. Hum Reprod 18(12):2599–2602CrossRefGoogle Scholar
  5. 5.
    Galinier P, Carfagna L, Delsol M, Ballouhey Q, Lemasson F, Le Mandat A, Moscovici J, Guitard J, Pienkowski C, Vaysse P (2009) Ovarian torsion. Management and ovarian prognosis: a report of 45 cases. J Pediatr Surg 44(9):1759–1765. CrossRefGoogle Scholar
  6. 6.
    Borekci B, Gundogdu C, Altunkaynak BZ, Calik M, Altunkaynak ME, Unal D, Unal B (2009) The protective effect of dehydroepiandrosterone on ovarian tissues after torsion-detorsion injury: a stereological and histopathological study. Eurasian J Med 41(1):22–27Google Scholar
  7. 7.
    Zhai Y, Petrowsky H, Hong JC, Busuttil RW, Kupiec-Weglinski JW (2013) Ischaemia-reperfusion injury in liver transplantation—from bench to bedside. Nat Rev Gastroenterol Hepatol 10(2):79–89. CrossRefGoogle Scholar
  8. 8.
    Limani P, Linecker M, Oberkofler CE, Barmettler G, Kaech A, Graf R, Humar B, Clavien PA (2016) Remote ischemic preconditioning: a novel strategy in rescuing older livers from ischemia-reperfusion injury in a rodent model. Ann Surg 264(5):797–803. CrossRefGoogle Scholar
  9. 9.
    Wang S, Li H, He N, Sun Y, Guo S, Liao W, Liao Y, Chen Y, Bin J (2017) Impact of remote ischaemic preconditioning on major clinical outcomes in patients undergoing cardiovascular surgery: a meta-analysis with trial sequential analysis of 32 randomised controlled trials. Int J Cardiol 227:882–891. CrossRefGoogle Scholar
  10. 10.
    Xia M, Ding Q, Zhang Z, Feng Q (2017) Remote limb ischemic preconditioning protects rats against cerebral ischemia via HIF-1alpha/AMPK/HSP70 pathway. Cell Mol Neurobiol 37(6):1105–1114. CrossRefGoogle Scholar
  11. 11.
    Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol Med 26(9–10):1231–1237CrossRefGoogle Scholar
  12. 12.
    Kruger E, Heller DS (1999) Adnexal torsion. A clinicopathologic review of 31 cases. J Reprod Med 44(2):71–75Google Scholar
  13. 13.
    Calis P, Bozdag G, Karakoc Sokmensuer L, Kender N (2015) Does ischemia-reperfusion injury affect ovarian reserve and follicle viability in a rat model with adnexal torsion? Eur J Obstet Gynecol Reprod Biol 185:126–130. CrossRefGoogle Scholar
  14. 14.
    Rody A, Jackisch C, Klockenbusch W, Heinig J, Coenen-Worch V, Schneider HP (2002) The conservative management of adnexal torsion—a case-report and review of the literature. Eur J Obstet Gynecol Reprod Biol 101(1):83–86CrossRefGoogle Scholar
  15. 15.
    Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551. CrossRefGoogle Scholar
  16. 16.
    Ozsoy AZ, Nursal AF, Arici A, Butun I, Uysal M, Irmak Sapmaz H, Kunt Isguder C, Yilmaz Dogru H, Tas U (2016) Effects of carvedilol on an ischemia/reperfusion model: biochemical, histopathological and immunohistochemical evaluation. J Obstet Gynaecol Res 42(9):1132–1140. CrossRefGoogle Scholar
  17. 17.
    Akdemir A, Sahin C, Erbas O, Yeniel AO, Sendag F (2015) Is ursodeoxycholic acid crucial for ischemia/reperfusion-induced ovarian injury in rat ovary? Arch Gynecol Obstet 292(2):445–450. CrossRefGoogle Scholar
  18. 18.
    Tokgoz VY, Sipahi M, Keskin O, Guvendi GF, Takir S (2018) Protective effects of vitamin D on ischemia-reperfusion injury of the ovary in a rat model. Iran J Basic Med Sci 21(6):593–599. Google Scholar
  19. 19.
    Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74(5):1124–1136CrossRefGoogle Scholar
  20. 20.
    Zhai Y, Busuttil RW, Kupiec-Weglinski JW (2011) Liver ischemia and reperfusion injury: new insights into mechanisms of innate-adaptive immune-mediated tissue inflammation. Am J Transplant 11(8):1563–1569. CrossRefGoogle Scholar
  21. 21.
    Petrowsky H, McCormack L, Trujillo M, Selzner M, Jochum W, Clavien PA (2006) A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Ann Surg 244(6):921–928. (Discussion 928–930) CrossRefGoogle Scholar
  22. 22.
    Gill R, Kuriakose R, Gertz ZM, Salloum FN, Xi L, Kukreja RC (2015) Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance. Mol Cell Biochem 402(1–2):41–49. CrossRefGoogle Scholar
  23. 23.
    Gassanov N, Nia AM, Caglayan E, Er F (2014) Remote ischemic preconditioning and renoprotection: from myth to a novel therapeutic option? J Am Soc Nephrol 25(2):216–224. CrossRefGoogle Scholar
  24. 24.
    Hausenloy DJ, Yellon DM (2008) Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res 79(3):377–386. CrossRefGoogle Scholar
  25. 25.
    Maulik N, Yoshida T, Das DK (1998) Oxidative stress developed during the reperfusion of ischemic myocardium induces apoptosis. Free Radical Biol Med 24(5):869–875CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyGiresun UniversityGiresunTurkey
  2. 2.Department of Emergency MedicineGiresun UniversityGiresunTurkey
  3. 3.Department of General SurgeryGiresun UniversityGiresunTurkey
  4. 4.Department of Medical BiochemistryGiresun UniversityGiresunTurkey
  5. 5.Biology Department of Council of Forensic MedicineIzmirTurkey
  6. 6.Department of Histology and EmbryologyEge UniversityIzmirTurkey

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