Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2014.01.002
Brazilian Journal of Anesthesiology
Scientific Article

Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia–reperfusion injury in rats

Efeitos de dexmedetomidina em conjunto com o pré-condicionamento isquêmico remoto em lesão de isquemia-reperfusão renal em ratos

Emine Bagcik; Sevda Ozkardesler; Nilay Boztas; Bekir Ugur Ergur; Mert Akan; Mehmet Guneli; Sule Ozbilgin

Downloads: 1
Views: 913

Abstract

Background and objectives: The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats. Methods: 28 Wistar albino male rats were divided into 4 groups. Group I (Sham, n = 7): Laparotomy and renal pedicle dissection were performed at 65th minute of anesthesia and the rats were observed under anesthesia for 130min. Group II (ischemia-reperfusion, n = 7): At 65th minute of anesthesia bilateral renal pedicles were clamped. After 60 min ischemia 24 h of reperfusion was performed. Group III (ischemia-reperfusion + dexmedetomidine, n = 7): At the fifth minute of reperfusion (100 μg/kg intra-peritoneal) dexmedetomidine was administered with ischemia-reperfusion group. Reperfusion lasted 24 h. Group IV (ischemia-reperfusion + remote ischemic preconditioning + dexmedetomidine, n = 7): After laparotomy, three cycles of ischemic preconditioning (10 min ischemia and 10 min reperfusion) were applied to the left hind limb and after 5 min with group III. Results: Histopathological injury scores and active caspase-3 immunoreactivity were significantly lower in the Sham group compared to the other groups. Histopathological injury scores in groups III and IV were significantly lower than group II (p = 0.03 and p = 0.05). Active caspase-3 immunoreactivity was significantly lower in the group IV than group II (p = 0.01) and there was no significant difference between group II and group III (p = 0.06). Conclusions: Pharmacologic conditioning with dexmedetomidine and remote ischemic preconditioning when combined with dexmedetomidine significantly decreases renal ischemia- reperfusion injury histomorphologically. Combined use of two methods prevents apoptosis via active caspase-3.

Keywords

Kidney, Ischemia-reperfusion injury, Dexmedetomidine, Caspase-3, Ischemic preconditioning, Apoptosis

Resumo

Justificativa e objetivos: Avaliar os efeitos do pré-condicionamento isquêmico remoto, mediante breve isquemia de membro posterior unilateral, em combinação com dexmedetomidina em lesão de isquemia-reperfusão renal por meio de histopatologia e imunorreatividade da caspase-3 ativa em ratos. Métodos: Foram divididos em quatro grupos 28 ratos machos albinos Wistar. Grupo I (Sham cirurgia controle], n = 7): laparotomia e dissecção do pedículo renal foram feitas em 65 minutos de anestesia e os ratos foram observados sob anestesia por 130 minutos. Grupo II (isquemia-reperfusão, n = 7): no 65° minuto de anestesia, os pedículos renais bilaterais foram pinçados; após 60 minutos de isquemia, foi feita reperfusão de 24 horas. Grupo III (isquemia-reperfusão + dexmedetomidina, n = 7): no quinto minuto de reperfusão, dexmedetomidina (100 mg/kg intraperitoneal) foi administrada ao grupo com isquemia-reperfusão. A reperfusão durou 24 horas. Grupo IV (isquemia-reperfusão + pré-condicionamento isquêmico remoto + dexmedetomidina, n = 7): após a laparotomia, três ciclos de pré-condicionamento isquêmico (10minutos de isquemia e 10minutos de reperfusão) foram aplicados no membro posterior esquerdo e depois de cincominutos ao grupo III. Resultados: Os escores de lesão histopatológica e imunorreatividade da caspase-3 ativa foram significativamente menores no grupo Sham em comparação com os outros. Os escores de lesão histopatológica dos grupos III e IV foram significativamente menores do que os do II (p = 0,03 e p = 0,05). A imunorreatividade da caspase-3 foi significativamente menor no grupo IV do que no II (p = 0,01) e não houve diferença significante entre os grupos II e III (p = 0,06). Conclusões: O condicionamento farmacológico com dexmedetomidina e o pré-condicionamento isquêmico remoto em combinação com dexmedetomidina diminuem de modo significante a lesão de isquemia-reperfusão renal histomorfologicamente. O uso combinado dos dois métodos previne a apoptose via caspase-3 ativa.

Palavras-chave

Rim, Lesão de isquemia-reperfusão, Dexmedetomidine, Caspase-3, Pré-condicionamento isquêmico, Apoptose

References

Ojo AO, Wolfe RA, Held PJ. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. ;63:974-968.

Perico N, Cattaneo D, Sayegh MH. Delayed graft function in kidney transplantation. Lancet. ;364:1814-1827.

Ojo AO, Held PJ, Port FK. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. ;349:931-940.

Nigwekar SU, Kandula P, Hix JK. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies. Am J Kidney Dis. ;54:423-413.

Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology. ;94:1133-1138.

Tsutsui H, Sugiura T, Hayashi K. Moxonidine prevents ischemia/reperfusion-induced renal injury in rats. Eur J Pharmacol. ;603:73-78.

Yazici P, Alizadehshargh S, Akdogan G. Apoptosis: regulatory molecules, relationships with diseases and apoptosis detection methods. Turkiye Klinikleri J Med Sci. ;29:1677-1686.

Faubel S, Edelstein CL. Caspases as drug targets in ischemic organ injury. Immune Endocr Metabol Disord. ;5:269-287.

Noiri E, Gailit J, Sheth D. Cyclic RGD peptides ameliorate ischemic acute renal failure in rats. Kidney Int. ;46:1050-1058.

Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int. ;66:486-491.

Tapuria N, Kumar Y, Habib MM. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury - a review. J Surg Res. ;150:304-330.

Kanoria S, Jalan R, Davies NA. Remote ischaemic preconditioning of the hind limb reduces experimental liver warm ischaemia-reperfusion injury. Br J Surg. ;93:762-768.

Duru S, Koca U, Oztekin S. Antithrombin III pretreatment reduces neutrophil recruitment into lung and skeletal muscle tissues in the rat model of bilateral lower limb ischaemia and reperfusion: a pilot study. Acta Anaesthesiol Scand. ;49:1142-1148.

Feng L, Xiong Y, Cheng F. Effect of ligustrazine on ischemia-reperfusion injury in murine kidney. Transplant Proc. ;36:1949-1951.

Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. ;334:1460-1448.

Brezis M, Rosen S, Silva P. Renal ischemia: a new perspective. Kidney Int. ;26:383-375.

Caron A, Desrosiers RR, Beliveau R. Kidney ischemia reperfusion regulates expression and distribution of tubulin subunits, beta-actin and rho GTPases in proximal tubules. Arch Biochem Biophys. ;431:46-31.

Gu J, Pamela S, Hailin Z. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. ;15:R153.

Kocoğlu H, Ozturk H, Ozturk H. Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: a histopathologic study. Ren Fail. ;31:74-70.

Williams P, Lopez H, Britt D. Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods. ;37:1-7.

Fujii T, Takaoka M, Muraoka T. Preventive effect of lcarnosine on ischemia/reperfusion-induced acute renal failure in rats. Eur J Pharmacol. ;474:261-267.

Hussein Ael-A, Shkeir AA, Sarhan ME. Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study. BJU Int. ;107:323-328.

Jaeschke H, Farhood A. Kupffer cell activation after no-flow ischemia versus hemorrhagic shock. Free Radic Biol Med. ;33:210-219.

Sanders RD, Maze M. Alpha 2-adrenoceptor agonists. Curr Opin Investig Drugs. ;8:33-25.

Billings FT, Chen SW, Kim M. Alpha 2-adrenergic agonists protect against radiocantrast-induced nephropathy in mice. Am J Physiol Renal Physiol. ;295:748-741.

Ma D, Hossain M, Rajakumaraswamy N. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Eur J Pharmacol. ;502:87-97.

Kuhmonen J, Pokorny J, Miettinen R. Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia. Anesthesiology. ;87:371-377.

Taoda M, Adachi YU, Uchihashi Y. Effect of dexmedetomidine on the release of 3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor. Neurochem Int. ;38:322-317.

Villela NR, Nascimento PVN, Carvalho LR. Effects of dexmedetomidine on renal system and on vasopressin plasma levels. Experimental study in dogs. Rev Bras Anestesiol. ;55:429-440.

Frumento RJ, Logginidou HG, Wahlander S. Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery. J Clin Anesth. ;18:422-426.

Kulka PJ, Tryba M, Zenz M. Preoperative alpha 2-adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial. Crit Care Med. ;24:947-952.

Helbo-Hansen S, Fletcher R, Lundberg D. Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery. Acta Anaesthesiol Scand. ;30:235-242.

Kulka PJ, Tryba M, Zenz M. Dose-response effects of intravenous clonidine on stress response during induction of anesthesia in coronary artery bypass graft patients. Anesth Analg. ;80:263-268.

Flacke JW, Bloor BC, Flacke WE. Reduced narcotic requirement by clonidine with improved hemodynamic and adrenergic stability in patients undergoing coronary bypass surgery. Anesthesiology. ;67:11-19.

Gesek FA. Alpha2-adrenergic receptors activate phospholipase C in renal epithelial cells. Mol Pharmacol. ;50:407-414.

O'Rourke B. Evidence for mitochondrial K+ channels and their role in cardioprotection. Circ Res. ;94:420-432.

Engelhard K, Werner C, Eberspacher E. The effect of the alpha 2-agonist dexmedetomidine and the N-methyldaspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg. ;96:524-531.

Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med. ;344:442-431.

Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. ;351:159-169.

Wever KE, Menting TP, Rovers M. Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis. PLoS ONE. ;7:e32296.

Venugopal V, Laing CM, Ludman A. Effect of remote ischemic preconditioning on acute kidney injury in nondiabetic patients undergoing coronary artery bypass graft surgery: a secondary analysis of 2 small randomized trials. Am J Kidney Dis. ;56:1043-1049.

Curtis FG, Vianna PT, Viero RM. Dexmedetomidine and S(+)-ketamine in ischemia and reperfusion injury in the rat kidney. Acta Cir Bras. ;26:202-206.

Diwan V, Kant R, Jaggi AS. Signal mechanism activated by erythropoietin preconditioning and remote renal preconditioning-induced cardioprotection. Mol Cell Biochem. ;315:195-201.

5dcd85260e88259666bf58f3 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections