Abstract
Purpose
A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in anin vivo experimental model of aortic surgery in comparison with sevoflurane.
Methods
Twenty young male piglets were anesthetized with either propofol 4 mg·kg-1·hr-1 (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-α, interleukin 1-ß, and interferon-γ; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed.
Results
In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-α, interleukin 1-ß, interferon-γ, super-oxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05).
Conclusion
In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting.
Abstract
Objectif
Un essai en laboratoire a été entrepris pour évaluer les effets du propofol sur la fonction rénale, à travers la modulation de la réaction inflammatoire généralisée, chez un modèle expérimental in vivo de chirurgie aortique et en comparaison avec le sévoflurane.
Méthode
Vingt jeunes porcelets ont été anesthésiés avec 4 mg·kg1·h-1 de propofol (n = 10) ou de sévoflurane à une concentration télé-expiratoire de 1,5 % (n = 10). Ils ont subi un pontage aorto-aortique avec clampage aortique pendant 30 min. À des moments spécifiques (au départ — avant le début de l’opération ; pendant la reperfusion 15 min après le déclampage de l’aorte ; à 24, 48 et 72 h après l’opération et au septième jour postopératoire), les niveaux suivants ont été déterminés : la créatinine plasmatique, la myéloperoxydase rénale, le facteur-α nécrosant tumoral, l’interleukine 1-ß et l’interféron-γ ; l’anion de superoxyde rénal et son enzyme de détoxification superoxydase dismutase, la malondialdéhyde rénale et l’activité de l’oxyde nitrique synthase inductible. Sept jours après l’opération, les animaux ont été anesthésiés selon les techniques décrites et, après le retrait du sang et la prise d’un échantillon rénal, ont été sacrifiés.
Résultats
Comparé au sévoflurane, le propofol a été associé à une plus faible concentration plasmatique de créatinine, (P < 0,05) et à de plus faibles concentrations de myéloperoxydase, de facteur-α nécrosant tumoral, d’interleukine 1-ß, d’interféron-γ, d’anion de superoxyde et de superoxyde dismutase, de malondial-déhyde et d’oxyde nitrique synthase inductible (P < 0,05).
Conclusion
Pour un modèle expérimental de reconstruction aortique, et comparé à l’anesthésie au sévoflurane, l’anesthésie au propofol est associée à moins d’infiltration de neutrophiles, à des niveaux plasmatiques inférieurs de cytokine pro-inflammatoire, à une plus faible production de radicaux libres d’oxygène, à moins de peroxydation lipidique et à une activité réduite de l’oxyde nitrique synthase inductible. Ces observations indiquent un effet rénal protecteur possible du propofol dans ce contexte chirurgical.
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References
Ross S, Foex P. Protective effects of anaesthetics in reversible and irreversible ischaemia-reperfusion injury. Br J Anaesth 1999; 82: 622–32.
Runzer TD, Ansley DM, Godin DV, Chambers GK. Tissue antioxidant capacity during anesthesia: propofol enhances in vivo red cell and tissue antioxidant capacity in a rat model. Anesth Analg 2002; 94: 89–93.
Huang CJ, Slovin PN, Nielsen RB, Skimming JW. Diprivan attenuates the cytotoxicity of nitric oxide in cultured human bronchial epithelial cells. Intensive Care Med 2002; 28: 1145–50.
Kato R, Foex P. Myocardial protection by anesthetic agents against ischemia-reperfusion injury: an updater for anesthesiologist. Can J Anesth 2002; 49: 777–91.
Ansley DM, Lee JU, Godin DV, Garnett ME, Qayumi AK. Propofol enhances red cell antioxidant capacity in swine and humans. Can J Anaesth 1998; 45: 233–9.
Murphy PG, Myers DS, Davies MJ, Webster NR, Jones JG. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth 1992; 68: 613–8.
Green TR, Bennett SR, Nelson VM. Specificity and properties of propofol as an antioxidant free radical scavenger. Toxicol Appl Pharmacol 1994; 129: 163–9.
Kahraman S, Demiryurek AT. Propofol is a peroxynitrite scavenger. Anesth Analg 1997; 84: 1127–9.
Mouithys-Mickalad A, Hans P, Deby-Dupont G, Hoebeke M, Deby C, Lamy M. Propofol reacts with peroxynitrite to form a phenoxyl radical: demonstration by electron spin resonance. Biochem Biophys Res Commun 1998; 249: 833–7.
Warltier DC, Al-Wathiqui MH, Kampine JP, Schmeling WT. Recovery of contractile function of stunned myocardium in chronically instrumented dogs is enhanced by halothane or isoflurane. Anesthesiology 1988; 69: 552–65.
Marijic J, Stowe DF, Turner LA, Kampine JP, Bosnjak ZJ. Differential protective effects of halothane and isoflurane against hypoxic and reoxigenation injury in the isolated guinea pig heart. Anesthesiology 1990; 73: 976–83.
Varadarajan SG, An J, Novalija E, Stowe DF. Sevoflurane before or after ischemia improves contractile and metabolic function while reducing myoplasmic Ca2+ loading in intact hearts. Anesthesiology 2002; 96: 125–33.
Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78: 206–9.
Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods 1985; 14: 157–67.
García-Criado FJ, Eleno N, Santos-Benito F, et al. Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion. Transplantation 1998; 66: 982–90.
Lozano FS, García-Criado FJ, Fresnadillo MJ, García E, García JE, Gómez-Alonso A. Systemic inflammatory response induced by dacron graft and modulation by antimicrobial agents: experimental study. J Surg Res 2002; 107: 7–13.
Forman HJ, Boveris A. Superoxide radical and hydrogen peroxide in mitochondria.In: Pryor WA (Ed.). Free Radicals in Biology, vol V. New York: Academic Press; 1982; 5: 65–90.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantites of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54.
Misra HP, Fridovich Υ. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247: 3170–5.
Ansley DM, Sun J, Visser WA, et al. High dose propofol enhances red cell antioxidant capacity during CBP in humans. Can J Anesth 1999; 46: 641–8.
Υoo KΥ, Υang SΥ, Lee J, et al. Intracoronary propofol attenuates myocardial but not coronary endothelial dysfunction after brief ischaemia and reperfusion in dogs. Br J Anaesth 1999; 82: 90–6.
Cheng ΥJ, Wang ΥP, Chien CT, Chen CF. Small-dose propofol sedation attenuates the formation of reactive oxygen species in tourniquet-induced ischemia-reperfusion injury under spinal anesthesia. Anesth Analg 2002; 94: 1617–20.
Bao ΥP, Williamson G, Tew D, et al. Antioxidant effects of propofol in human hepatic microsomes: concentration effects and clinical relevance. Br J Anaesth 1998; 81: 584–9.
De La Cruz JP, Villalobos MA, Sedeño G, Sánchez de la CuestaF. Effect of propofol on oxidative stress in an in vitro model of anoxia-reoxygenation in the rat brain. Brain Res 1998; 800: 136–44.
De La Cruz JP, Sedeño G, Carmona JA, Sánchez de la Cuesta F. The in vitro effects of propofol on tissular oxidative stress in the rat. Anesth Analg 1998; 87: 1141–6.
Corcoran TB, Engel A, Sakamoto H, et al. The effects of propofol on lipid peroxidation and inflammatory response in elective coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2004; 18: 592–604.
Grasshoff C, Gillessen T. The effect of propofol on increased superoxide concentration in cultured rat cerebrocortical neurons after stimulation of N-methyl-Daspartate receptors. Anesth Analg 2002; 95: 920–2.
Ross S, Muñoz H, Piriou V, Ryder A, Foex P. A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning. Acta Anaesthesiol Scand 1998; 42: 23–31.
Ebel D, Schlack W, Comfere T, Preckel B, Thamer V. Effect of propofol on reperfusion injury after regional ischaemia in the isolated rat heart. Br J Anaesth 1999; 83: 903–8.
Javadov SA, Lim KH, Kerr PM, Suleiman MS, Angelini GD, Halestrap AP. Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition. Cardiovasc Res 2000; 45: 360–9.
Kowalski C, Zahler S, Becker BF, et al. Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system. Anesthesiology 1997; 86: 188–95.
Heindl B, Reichle FM, Zahler S, Conzen PF, Becker BF. Sevoflurane and isoflurane protect the reperfused guinea pig heart by reducing postischemic adhesion of polymorphonuclear neutrophils. Anesthesiology 1999; 91: 521–30.
De Hert SG, ten Broecke PW, Mertens E, et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology 2002; 97: 42–9.
García-Criado FJ, Palma-Vargas JM, Valdunciel JJ, et al. Tacrolimus (FK506) down-regulates free radical tissue levels, serum cytokines, and neutrophil infiltration after severe liver ischemia. Transplantation 1997; 64: 594–8.
MacNaul KL, Hutchinson NI. Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle cells and endothelial cells under normal and inflammatory conditions. Biochem Biophys Res Commun 1993; 196: 1330–4.
Beasley D, Schwartz JH, Brenner BM. Interleukin-1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. J Clin Invest 1991; 87: 602–8.
Balligand JL, Ungureanu-Longrois D, Simmons WW, et al. Induction of NO synthase in rat cardiac microvascular endothelial cells by IL-1ß and INF-γ. Am J Physiol 1995; 268: H1293–303.
Wang P, Zweier JL. Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitrite-mediated reperfusion injury. J Biol Chem 1996; 271: 29223–30.
Xie QW, Kashiwabara Y, Nathan C. Role of transcription factor NF- êB/Rel in induction of nitric oxide synthase. J Biol Chem 1994; 269: 4705–8.
Chen RM, Wu GJ, Tai ΥT, et al. Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase. Arch Toxicol 2003; 77: 418–23.
Lowenthal JW, Ballard DW, Bohnlein E, Greene WC. Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes. Proc Natl Acad Sci USA 1989; 86: 2331–5.
Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci USA 1989; 86: 2336–40.
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An erratum to this article is available at http://dx.doi.org/10.1007/BF03022848.
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Rodríguez-López, J.M., Sánchez-Conde, P., Lozano, F.S. et al. Laboratory investigation: Effects of propofol on the systemic inflammatory response during aortic surgery. Can J Anesth 53, 701–710 (2006). https://doi.org/10.1007/BF03021629
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DOI: https://doi.org/10.1007/BF03021629