Effect of reperfusion injury from distant ischemia to small intestine
BACKGROUND The ileum is the most vulnerable part of the small intestine that plays an important role as the motor of multisystem organ failure. Villous damage is demonstrated after ligation of supply artery in mice; however, there is no study on the ileum after distant ischemic organs. Thus, this study was aimed to find out ileal villous changes following reperfusion injury, the protective effects of ischemic hypothermia and ischemic preconditioning.
METHODS An experimental study conducted enrolled 21 subjects of Oryctolagus cuniculus. Ischemia is induced by ligation of the femoral artery for 4 hours. Eight hours after ligation was released, ileum and duodenal specimens were taken through laparotomy. H&E stained specimens were examined for histomorphological changes. Villi change scores, tissue level of hypoxia-inducible factor-1α (HIF-1α), malondialdehyde (MDA), and occludin were statistically analyzed in four treatment groups, namely ischemia, ischemic hypothermia, ischemic preconditioning, and control.
RESULTS Intestinal villi changes were found following ischemic-induced arterial ligation. Ileal villi changes showed differences with the duodenum and controls as indicated by the villi damage scores, increased tissue HIF-1α and MDA, and decreased occludin levels. Ileal villi changes in the ischemic and ischemic hypothermia groups showed significant changes with controls; whereas the ischemic preconditioning group showed no significant differences.
CONCLUSIONS Ischemia at a distance leads to both histomorphological and biochemical damage of the ileal villi and disrupts the integrity of the intestinal mucosal barrier. In addition, the study showed a protective effect of ischemic preconditioning.
Carden DL, Granger DN. Pathophysiology of ischemia-reperfusion injury. J Pathol. 2000;190(3):255–66. https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6
Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion Injury. Anesthesiology. 2001;94(6):1133–8. https://doi.org/10.1097/00000542-200106000-00030
Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull. 2004;70:71–86. https://doi.org/10.1093/bmb/ldh025
Leaphart CL, Tepas JJ. The gut is a motor of organ system dysfunction. Surgery. 2007;141(5):563–9. https://doi.org/10.1016/j.surg.2007.01.021
Sertaridou E, Papaioannou V, Kolios G, Pneumatikos I. Gut failure in critical care: old school versus new school. Ann Gastroenterol. 2015;28(3):309–22.
Schofield Z, Woodruff TM, Halai R, Wu MC, Cooper MA. Neutrophils–a key component of ischemia-reperfusion injury. Shock. 2013;40(6):463–70. https://doi.org/10.1097/SHK.0000000000000044
Zhu J, Fu Y, Jiang J, Liang JK, Huang ZT. Therapeutic hypothermia reduces intestinal ischemia/reperfusion injury after cardiac arrest in rats. Afr Journal Biothecnol. 2011;10(38):7497–502. https://doi.org/10.5897/AJB11.166
Zhang B, Zhao Y, Bao L, Wang LH, Guo HB, Zhang WX, et al. Protective effects of remote limb preconditioning on ischemia reperfusion injury in rats liver. J Gastroenterol Hepatol Res. 2013;2(9):791–4. https://doi.org/doi:10.6051/j.issn.2224-3992.2013.02.324
Moore EM, Nichol AD, Bernard SA, Bellomo R. Therapeutic hypothermia: benefits, mechanisms and potential clinical applications in neurological, cardiac and kidney injury. Injury. 2011;42(9):843–54. https://doi.org/10.1016/j.injury.2011.03.027
Erling Junior N, Montero EF, Sannomiya P, Poli-de-Figueiredo LF. Local and remote ischemic preconditioning protect against intestinal ischemic/reperfusion injury after supraceliac aortic clamping. Clinics (Sao Paulo). 2013;68(12):1548–54. https://doi.org/10.6061/clinics/2013(12)12
Weis CP, LaVelle JM. Characteristics to consider when choosing an animal model for the study of lead bioavailability. Chem Speciat Bioavailab. 1991;3(3–4):113–9. https://doi.org/10.1080/09542299.1991.11083162
Zhang Y, Wu YX, Hao YB, Dun Y, Yang SP. Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine. Life Sci. 2001;68(9):1013–9. https://doi.org/10.1016/S0024-3205(00)01004-3
Oltean M, Olausson M. The Chiu/Park scale for grading intestinal ischemia–reperfusion: if it ain't broke don't fix it! Intensive Care Med. 2010;36(6):1095. https://doi.org/10.1007/s00134-010-1811-y
Elli L, Zini E, Tomba C, Bardella MT, Bosari S, Conte D, et al. Histological evaluation of duodenal biopsies from coeliac patients: the need for different grading criteria during follow-up. BMC Gastroenterol. 2015;15:133. https://doi.org/10.1186/s12876-015-0361-8
Semenza GL. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology. 2004;19(4):176–82. https://doi.org/10.1152/physiol.00001.2004
Ikeda H, Suzuki Y, Suzuki M, Koike M, Tamura J, Tong J, et al. Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium. Gut. 1998;42(4):530–7. https://doi.org/10.1136/gut.42.4.530
Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology. 2000;7(3):153–63. https://doi.org/10.1016/S0928-4680(00)00053-5
Guan Y, Worrell RT, Pritts TA, Montrose MH. Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo. Am J Physiol Gastrointest Liver Physiol. 2009;297(1):G187–96. https://doi.org/10.1152/ajpgi.90595.2008
Moore-Olufemi SD, Olufemi SE, Lott S, Sato N, Kozar RA, Moore FA, et al. Intestinal ischemic preconditioning after ischemia/reperfusion injury in rat intestine: profiling global gene expression patterns. Dig Dis Sci. 2010;55(7):1866–77. https://doi.org/10.1007/s10620-009-0980-4
Brzozowski T, Konturek PC, Konturek SJ Pajdo R, Kwiecien S, Pawlik M, et al. Ischemic preconditioning of remote organs attenuates gastric ischemia-reperfusion injury through involvement of prostaglandins and sensory nerves. Eur J Pharmacol. 2004;499(1–2):201–13. https://doi.org/10.1016/j.ejphar.2004.07.072
Tyagi P, Tayal G. Ischemic preconditioning of myocardium. Acta Pharmacol Sin. 2002;23(10):865–70.
Shah TA, Mauriello CT, Hair PS, Sandhu A, Stolz MP, Bass WT, et al. Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway. J Transl Med. 2014;12:181. https://doi.org/10.1186/1479-5876-12-181
Graham ML, Prescott MJ. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease. Eur J Pharmacol. 2015;759:19–29. https://doi.org/10.1016/j.ejphar.2015.03.040
Mapara M, Thomas BS, Bhat KM. Rabbit as an animal model for experimental research. Dent Res J (Isfahan). 2012;9(1):111–8. https://doi.org/10.4103/1735-3327.92960
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