Remifentanil ameliorates intestinal ischemia-reperfusion injury

BMC Gastroenterology

Claudia A Nold-Petry³  Wei Cheng²  Marcel F Nold³  Michael G Irwin¹  Philip J Berger³  Ina Rudloff³  Steven SC Cho³ 

[1] Department of Anaesthesiology, University of Hong Kong, Hong Kong, China;Department of Paediatrics and Department of Surgery, Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia;The Ritchie Centre, Monash Institute of Medical Research, Monash University, Melbourne, Australia

关键词: Preconditioning;    Remifentanil;    Opioid;    Mouse;    Intestine;    Reperfusion;    Ischemia;   

Others  :  858051
DOI  :  10.1186/1471-230X-13-69

 received in 2012-09-01, accepted in 2013-04-11,  发布年份 2013

【 摘 要 】

Background

Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as organ transplantation, trauma and cardio-pulmonary bypass, as well as in neonatal necrotizing enterocolitis or persistent ductus arteriosus. Pharmacological protection by pretreating (“preconditioning”) with opioids attenuates IRI in a number of organs. Remifentanil appears particularly attractive for this purpose because of its ultra-short duration of action and favorable safety profile. To date, little is known about opioid preconditioning of the intestine.

Methods

Young adult C57BL/6J mice were randomly assigned to receive tail vein injections of 1 μg/kg of remifentanil or normal saline and underwent either ischemia-reperfusion of the intestine or a sham laparotomy. Under isoflurane anesthesia, the mice were subjected to intestinal ischemia-reperfusion by occlusion (clamping) of the superior mesenteric artery for 30 min, followed by unclamping and 60 min of reperfusion. After completion of this protocol, tissue injury and lipid peroxidation in jejunum and ileum were analyzed by histology and malondialdehyde (MDA), respectively. Systemic interleukin (IL)-6 was determined in the plasma by ELISA.

Results

Pretreatment with remifentanil markedly reduced intestinal IRI (P < 0.001): In the ileum, we observed a more than 8-fold decrease in injured villi (4% vs 34% in saline-pretreated animals). In fact, the mucosa in the remifentanil group was as healthy as that of sham-operated animals. This protective effect was not as pronounced in the jejunum, but the percentage of damaged villi was still reduced considerably (18% vs 42%). There was up to 3-fold more tissue MDA after intestinal ischemia-reperfusion than after sham laparotomy, but this increase in lipid peroxidation was prevented by preconditioning with remifentanil (P < 0.05). The systemic inflammatory response triggered by intestinal IRI was significantly attenuated in mice pretreated with remifentanil (159 vs 805 pg/ml of IL-6 after saline pretreatment, with 92 pg/ml in the sham groups). After sham operations, no difference was detected between the saline- and remifentanil-pretreatments in any of the parameters investigated.

Conclusion

Preconditioning with remifentanil attenuates intestinal IRI and the subsequent systemic inflammatory response in mice. We therefore suggest that prophylaxis with this ultra-short-acting opioid may be advantageous in various clinical scenarios of human IRI.

【 授权许可】

   
2013 Cho et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Mallick IH, Yang W, Winslet MC, Seifalian AM: Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004, 49(9):1359-1377.
• [2]Granger DN, Rutili G, McCord JM: Superoxide radicals in feline intestinal ischemia. Gastroenterology 1981, 81(1):22-29.
• [3]Bodwell W: Ischemia, reperfusion, and reperfusion injury: role of oxygen free radicals and oxygen free radical scavengers. J Cardiovasc Nurs 1989, 4(1):25-32.
• [4]Carden DL, Granger DN: Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000, 190(3):255-266.
• [5]Murry CE, Jennings RB, Reimer KA: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986, 74(5):1124-1136.
• [6]de Perrot M, Liu M, Waddell TK, Keshavjee S: Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 2003, 167(4):490-511.
• [7]Bonventre JV: Kidney ischemic preconditioning. Curr Opin Nephrol Hypertens 2002, 11(1):43-48.
• [8]Rudiger HA, Kang KJ, Sindram D, Riehle HM, Clavien PA: Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver. Ann Surg 2002, 235(3):400-407.
• [9]Kitagawa K, Matsumoto M, Tagaya M, Hata R, Ueda H, Niinobe M, Handa N, Fukunaga R, Kimura K, Mikoshiba K: 'Ischemic tolerance' phenomenon found in the brain. Brain Res 1990, 528(1):21-24.
• [10]Sirin BH, Ortac R, Cerrahoglu M, Saribulbul O, Baltalarli A, Celebisoy N, Iskesen I, Rendeci O: Ischaemic preconditioning reduces spinal cord injury in transient ischaemia. Acta Cardiol 2002, 57(4):279-285.
• [11]Hotter G, Closa D, Prados M, Fernandez-Cruz L, Prats N, Gelpi E, Rosello-Catafau J: Intestinal preconditioning is mediated by a transient increase in nitric oxide. Biochem Biophys Res Commun 1996, 222(1):27-32.
• [12]Habibey R, Pazoki-Toroudi H: Morphine dependence protects rat kidney against ischaemia-reperfusion injury. Clin Exp Pharmacol Physiol 2008, 35(10):1209-1214.
• [13]Zhao P, Huang Y, Zuo Z: Opioid preconditioning induces opioid receptor-dependent delayed neuroprotection against ischemia in rats. J Neuropathol Exp Neurol 2006, 65(10):945-952.
• [14]Schultz JE, Hsu AK, Gross GJ: Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart. Circ Res 1996, 78(6):1100-1104.
• [15]Minguet G, Joris J, Lamy M: Preconditioning and protection against ischaemia-reperfusion in non-cardiac organs: a place for volatile anaesthetics? Eur J Anaesthesiol 2007, 24(9):733-745.
• [16]Peart JN, Gross ER, Gross GJ: Opioid-induced preconditioning: recent advances and future perspectives. Vascul Pharmacol 2005, 42(5–6):211-218.
• [17]Hacioglu A, Algin C, Pasaoglu O, Pasaoglu E, Kanbak G: Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine. BMC Gastroenterol 2005, 5:37. BioMed Central Full Text
• [18]Collard CD, Gelman S: Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 2001, 94(6):1133-1138.
• [19]Dorweiler B, Pruefer D, Andrasi T, Maksan S, Schmiedt W, Neufang A, Vahl C: Ischemia-Reperfusion Injury. Eur J Trauma Emerg Surg 2007, 33(6):600-612.
• [20]Chun KJ, Park YH, Kim JS, Jang Y, Kim JH, Kim J, Lee MY: Comparison of 5 different remifentanil strategies against myocardial ischemia-reperfusion injury. J Cardiothorac Vasc Anesth 2011, 25(6):926-930.
• [21]Yang LQ, Tao KM, Liu YT, Cheung CW, Irwin MG, Wong GT, Lv H, Song JG, Wu FX, Yu WF: Remifentanil preconditioning reduces hepatic ischemia-reperfusion injury in rats via inducible nitric oxide synthase expression. Anesthesiology 2011, 114(5):1036-1047.
• [22]Zhang Y, Irwin MG, Wong TM: Remifentanil preconditioning protects against ischemic injury in the intact rat heart. Anesthesiology 2004, 101(4):918-923.
• [23]Kim HS, Cho JE, Hong SW, Kim SO, Shim JK, Kwak YL: Remifentanil protects myocardium through activation of anti-apoptotic pathways of survival in ischemia-reperfused rat heart. Physiol Res 2010, 59(3):347-356.
• [24]Vianna PT, Castiglia YM, Braz JR, Viero RM, Beier S, Vianna Filho PT, Vitoria A, Reinoldes Bizarria Guilherme G, de Assis Golim M, Deffune E: Remifentanil, isoflurane, and preconditioning attenuate renal ischemia/reperfusion injury in rats. Transplant Proc 2009, 41(10):4080-4082.
• [25]Wong GT, Huang Z, Ji S, Irwin MG: Remifentanil reduces the release of biochemical markers of myocardial damage after coronary artery bypass surgery: a randomized trial. J Cardiothorac Vasc Anesth 2010, 24(5):790-796.
• [26]Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN: Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970, 101(4):478-483.
• [27]Armstrong D, Browne R: The analysis of free radicals, lipid peroxides, antioxidant enzymes and compounds related to oxidative stress as applied to the clinical chemistry laboratory. Adv Exp Med Biol 1994, 366:43-58.
• [28]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):1013-1019.
• [29]Stroumpos C, Manolaraki M, Paspatis GA: Remifentanil, a different opioid: potential clinical applications and safety aspects. Expert Opin Drug Saf 2010, 9(2):355-364.
• [30]Wong GT, Li R, Jiang LL, Irwin MG: Remifentanil post-conditioning attenuates cardiac ischemia-reperfusion injury via kappa or delta opioid receptor activation. Acta Anaesthesiol Scand 2010, 54(4):510-518.
• [31]Fukuyama K, Iwakiri R, Noda T, Kojima M, Utsumi H, Tsunada S, Sakata H, Ootani A, Fujimoto K: Apoptosis induced by ischemia-reperfusion and fasting in gastric mucosa compared to small intestinal mucosa in rats. Dig Dis Sci 2001, 46(3):545-549.
• [32]Maulik N, Engelman RM, Rousou JA, Flack JE 3rd, Deaton D, Das DK: Ischemic preconditioning reduces apoptosis by upregulating anti-death gene Bcl-2. Circulation 1999, 100(19 Suppl):II369-II375.
• [33]Cinel I, Avlan D, Cinel L, Polat G, Atici S, Mavioglu I, Serinol H, Aksoyek S, Oral U: Ischemic preconditioning reduces intestinal epithelial apoptosis in rats. Shock 2003, 19(6):588-592.
• [34]Kirkland RA, Windelborn JA, Kasprzak JM, Franklin JL: A Bax-induced pro-oxidant state is critical for cytochrome c release during programmed neuronal death. J Neurosci 2002, 22(15):6480-6490.
• [35]Mercer DW, Smith GS, Cross JM, Russell DH, Chang L, Cacioppo J: Effects of lipopolysaccharide on intestinal injury; potential role of nitric oxide and lipid peroxidation. J Surg Res 1996, 63(1):185-192.
• [36]Kim M, Park SW, D'Agati VD, Lee HT: Isoflurane post-conditioning protects against intestinal ischemia-reperfusion injury and multiorgan dysfunction via transforming growth factor-beta1 generation. Ann Surg 2012, 255(3):492-503.
• [37]Vollmar B, Menger MD: Intestinal ischemia/reperfusion: microcirculatory pathology and functional consequences. Langenbecks Arch Surg 2011, 396(1):13-29.
• [38]Collard CD, Lekowski R, Jordan JE, Agah A, Stahl GL: Complement activation following oxidative stress. Mol Immunol 1999, 36(13–14):941-948.
• [39]Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL: A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy. Anaesth Intensive Care 2008, 36(1):74-78.
• [40]von Dossow V, Luetz A, Haas A, Sawitzki B, Wernecke KD, Volk HD, Spies CD: Effects of remifentanil and fentanyl on the cell-mediated immune response in patients undergoing elective coronary artery bypass graft surgery. J Int Med Res 2008, 36(6):1235-1247.
• [41]Wei W, Fuhong T, Xinjing Z, Guixia J: Effect of remifentanil on toll-like receptor 4, NF-κB and IL-6 in rabbit myocardial ischemia/reperfusion model. Journal of Medical Colleges of PLA 2012, 27(3):134-142.
• [42]Balk RA: Pathogenesis and management of multiple organ dysfunction or failure in severe sepsis and septic shock. Crit Care Clin 2000, 16(2):337-352. vii
• [43]Jarrar D, Chaudry IH, Wang P: Organ dysfunction following hemorrhage and sepsis: mechanisms and therapeutic approaches (Review). Int J Mol Med 1999, 4(6):575-583.
• [44]Deitch EA, Goodman ER: Prevention of multiple organ failure. Surg Clin North Am 1999, 79(6):1471-1488.
• [45]Kong SE, Blennerhassett LR, Heel KA, McCauley RD, Hall JC: Ischaemia-reperfusion injury to the intestine. Aust N Z J Surg 1998, 68(8):554-561.
• [46]Sacerdote P, Gaspani L, Rossoni G, Panerai AE, Bianchi M: Effect of the opioid remifentanil on cellular immune response in the rat. Int Immunopharmacol 2001, 1(4):713-719.
• [47]Sharp BM, Roy S, Bidlack JM: Evidence for opioid receptors on cells involved in host defense and the immune system. J Neuroimmunol 1998, 83(1–2):45-56.
• [48]Bidlack JM, Khimich M, Parkhill AL, Sumagin S, Sun B, Tipton CM: Opioid receptors and signaling on cells from the immune system. J Neuroimmune Pharmacol 2006, 1(3):260-269.
• [49]Blackwell TS, Christman JW: The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 1997, 17(1):3-9.
• [50]Wang J, Barke RA, Charboneau R, Roy S: Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. J Immunol 2005, 174(1):426-434.
• [51]Cao Z, Liu L, Van Winkle DM: Met5-enkephalin-induced cardioprotection occurs via transactivation of EGFR and activation of PI3K. Am J Physiol Heart Circ Physiol 2005, 288(4):H1955-H1964.
• [52]Gross ER, Hsu AK, Gross GJ: Opioid-induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ Res 2004, 94(7):960-966.
• [53]Fryer RM, Patel HH, Hsu AK, Gross GJ: Stress-activated protein kinase phosphorylation during cardioprotection in the ischemic myocardium. Am J Physiol Heart Circ Physiol 2001, 281(3):H1184-H1192.
• [54]Zhao G, Chen ZC, Shen X, Chen YL, Lv Y: [Protective effect of remifentanil preconditioning against hepatic ischemia-reperfusion injury in rats: role of p38 mitogen-activated protein kinases]. Nan Fang Yi Ke Da Xue Xue Bao 2011, 31(12):2016-2020.
• [55]Zhang Y, Gu EW, Zhang J, Chen ZW: Role of p38 mitogen-activated protein kinases in cardioprotection of morphine preconditioning. Chin Med J (Engl) 2007, 120(9):777-781.
• [56]Fryer RM, Hsu AK, Gross GJ: ERK and p38 MAP kinase activation are components of opioid-induced delayed cardioprotection. Basic Res Cardiol 2001, 96(2):136-142.
• [57]Yue TL, Wang C, Gu JL, Ma XL, Kumar S, Lee JC, Feuerstein GZ, Thomas H, Maleeff B, Ohlstein EH: Inhibition of extracellular signal-regulated kinase enhances Ischemia/Reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res 2000, 86(6):692-699.
• [58]Bingham D, John CM, Levin J, Panter SS, Jarvis GA: Post-injury conditioning with lipopolysaccharide or lipooligosaccharide reduces inflammation in the brain. J Neuroimmunol 2013, 256(1–2):28-37.
• [59]Merry HE, Wolf PS, Fitzsullivan E, Keech JC, Mulligan MS: Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury. J Heart Lung Transplant 2010, 29(4):471-478.