Impact of different anesthetic protocols during anesthesia for the establishment of a porcine model of acute kidney injury

Axel Guilpin , Mathieu Magnin , Axel Aigle , Timothée Schuhler , Jean-Yves Ayoub , Romain Lac , Charlotte Slek , Thomas Brichart , Abdessalem Hammed , Vanessa Louzier

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (8) : 1493 -1502.

PDF
Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (8) :1493 -1502. DOI: 10.1002/ame2.70014
ORIGINAL ARTICLE

Impact of different anesthetic protocols during anesthesia for the establishment of a porcine model of acute kidney injury

Author information +
History +
PDF

Abstract

Background: During the establishment of a model of acute kidney injury (AKI) in pigs, we observed a high prevalence of malignant hyperthermia (MH). These complications led us to refine the anesthetic protocol. This publication describes the impact of the choice of anesthetics on the results obtained.

Methods: Pigs were euthanized at the end of the procedure, without recovery from anesthesia. Three anesthetic protocols were used: sevoflurane inhalation (ProtocolA, n = 5), a combination of ketamine, medetomidine and diazepam by intravenous infusion (ProtocolB, n = 5), and a combination of ketamine, diazepam, medetomidine, glucose, and noradrenaline (ProtocolC, n = 5). All pigs received morphine for analgesia. AKI was induced by interrupting renal perfusion for 90 min. MH was diagnosed based on clinical and biological parameters.

Results: All MH pigs belonged to ProtocolA. MH pigs showed significantly higher maximum rectal temperature (p = 0.04), maximum expired carbon dioxide (CO2; p = 0.04), maximum heart rate (HR; p = 0.03), plasma concentration of creatinine and potassium (p < 0.0001). Protocol A pigs had a significantly higher maximum HR (p = 0.01) and hyperkalemia compared to the two other groups (ProtocolB, p = 0.005 and ProtocolC, p < 0.0001). Pigs from ProtocolA had a significantly lower minimum mean arterial pressure (MAP) than ProtocolC group (p = 0.03) and MAP remained below 60 mmHg for longer (p = 0.004). In ProtocolB, minimum glycemia was lower than other groups (p = 0.01).

Conclusion: Sevoflurane use was associated with the occurrence of MH, hemodynamic alterations and changes in plasma concentration of creatinine and potassium. These modifications can have a major impact on the validation of an experimental AKI model.

Keywords

acute kidney injury / anesthesia / ketamine / malignant hyperthermia / sevoflurane

Cite this article

Download citation ▾
Axel Guilpin, Mathieu Magnin, Axel Aigle, Timothée Schuhler, Jean-Yves Ayoub, Romain Lac, Charlotte Slek, Thomas Brichart, Abdessalem Hammed, Vanessa Louzier. Impact of different anesthetic protocols during anesthesia for the establishment of a porcine model of acute kidney injury. Animal Models and Experimental Medicine, 2025, 8(8): 1493-1502 DOI:10.1002/ame2.70014

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Davidson MK, Lindsey JR, Davis JK. Requirements and selection of an animal model. Isr J Med Sci. 1987; 23(6): 551-555.

[2]

Domínguez-Oliva A, Hernández-Ávalos I, Martínez-Burnes J, Olmos-Hernández A, Verduzco-Mendoza A, Mota-Rojas D. The importance of animal models in biomedical research: current insights and applications. Animals. 2023; 13(7): 1223.

[3]

Robinson NB, Krieger K, Khan FM, et al. The current state of animal models in research: a review. Int J Surg. 2019; 72: 9-13.

[4]

Jirkof P. Side effects of pain and analgesia in animal experimentation. Lab Anim. 2017; 46(4): 123-128.

[5]

Cicero L, Fazzotta S, Palumbo VD, Cassata G, Lo Monte AI. Anesthesia protocols in laboratory animals used for scientific purposes. Acta Biomed Atenei Parm. 2018; 89(3): 337-342.

[6]

Layton R, Layton D, Beggs D, Fisher A, Mansell P, Stanger KJ. The impact of stress and anesthesia on animal models of infectious disease. Front Vet Sci. 2023; 10: 1086003.

[7]

Huang J, Bayliss G, Zhuang S. Porcine models of acute kidney injury. Am J Physiol Renal Physiol. 2021; 320(6): F1030-F1044.

[8]

Sun LY, Wijeysundera DN, Tait GA, Beattie WS. Association of Intraoperative Hypotension with acute kidney injury after elective noncardiac surgery. Anesthesiology. 2015; 123(3): 515-523.

[9]

Walsh M, Devereaux PJ, Garg AX, et al. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery. Anesthesiology. 2013; 119(3): 507-515.

[10]

Musk GC. Anaesthetising pigs. Vet Rec. 2015; 177(4): 96-97.

[11]

Pehböck D, Dietrich H, Klima G, Paal P, Lindner KH, Wenzel V. Anesthesia in swine: optimizing a laboratory model to optimize translational research. Anaesthesist. 2015; 64(1): 65-70.

[12]

Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015; 10(1): 93.

[13]

Guilpin A, Magnin M, Aigle A, et al. Temporary bilateral clamping of renal arteries induces ischemia-reperfusion: a new pig model of acute kidney injury using total intravenous anesthesia. Physiol Rep. 2025; 13: e70203.

[14]

Massoth C, Zarbock A, Meersch M. Acute kidney injury in cardiac surgery. Crit Care Clin. 2021; 37(2): 267-278.

[15]

Uhlig C, Labus J. Volatile versus intravenous anesthetics in cardiac anesthesia: a narrative review. Curr Anesthesiol Rep. 2021; 11(3): 275-283.

[16]

De Wit F, Van Vliet AL, De Wilde RB, et al. The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances. Br J Anaesth. 2016; 116(6): 784-789.

[17]

Englehart MS, Allison CE, Tieu BH, et al. Ketamine-based Total intravenous anesthesia versus isoflurane anesthesia in a swine model of hemorrhagic shock. J Trauma. 2008; 65(4): 901-909.

[18]

Boschert K, Flecknell PA, Fosse RT, et al. Ketamine and its use in the pig: recommendations of the consensus meeting on ketamine Anaesthesia in pigs, Bergen 1994. Lab Anim. 1996; 30(3): 209-219.

[19]

Wedel DJ, Laizzo PA, Milde JH. Desflurane is a trigger of malignant hyperthermia in susceptible swine. Anesthesiology. 1991; 74(3): 508-512.

[20]

Migita T, Mukaida K, Kobayashi M, Hamada H, Kawamoto M. The severity of sevoflurane-induced malignant hyperthermia: sevoflurane-induced malignant hyperthermia. Acta Anaesthesiol Scand. 2012; 56(3): 351-356.

[21]

Turhan KSC, Baytaş V, Batislam Y, Özatamer O. Delayed onset malignant hyperthermia after sevoflurane. Case Rep Anesthesiol. 2013; 2013: 712710.

[22]

Hopkins PM. Malignant hyperthermia: pharmacology of triggering. Br J Anaesth. 2011; 107(1): 48-56.

[23]

Hsu SC, Huang WT, Yeh HM, Hsieh AYJ. Suspected malignant hyperthermia during sevoflurane anesthesia. J Chin Med Assoc. 2007; 70(11): 507-510.

[24]

Lee JY, Jee HC, Jeong SM, Park CS, Kim MC. Comparison of anaesthetic and cardiorespiratory effects of xylazine or medetomidine in combination with tiletamine/zolazepam in pigs. Vet Rec. 2010; 167(7): 245-249.

[25]

Shulman M, Braverman B, Ivankovich AD, Gronert G. Sevoflurane triggers malignant hyperthermia in swine. Anesthesiology. 1981; 54(3): 259-260.

[26]

Gronert GA, Milde JH. Variations in onset of porcine malignant hyperthermia. Anesth Analg. 1981; 60(7): 499-503.

[27]

Wappler F. Anesthesia for patients with a history of malignant hyperthermia. Curr Opin Anaesthesiol. 2010; 23(3): 417-422.

[28]

Gregory H, Weant KA. Pathophysiology and treatment of malignant hyperthermia. Adv Emerg Nurs J. 2021; 43(2): 102-110.

[29]

Gong X. Malignant hyperthermia when dantrolene is not readily available. BMC Anesthesiol. 2021; 21(1): 119.

[30]

Krivosic-Horber R, Dépret T, Wagner JM, Maurage CA. Malignant hyperthermia susceptibility revealed by increased serum creatine kinase concentrations during statin treatment. Eur J Anaesthesiol. 2004; 21(7): 572-574.

[31]

Koseoglu M, Hur A, Atay A, Cuhadar S. Effects of hemolysis interference on routine biochemistry parameters. Biochem Med. 2011; 21: 79-85.

[32]

Sigg DC, Iaizzo PA. Malignant hyperthermia phenotype. Anesthesiology. 2000; 92(6): 1777-1788.

[33]

Ebert TJ, Harkin CP, Muzi M. Cardiovascular responses to sevoflurane: a review. Anesth Analg. 1995; 81: 11-22.

[34]

Lehman LW, Saeed M, Moody G, Mark R. Hypotension as a risk factor for acute kidney injury in ICU patients. Comput Cardiol. 2010; 37: 1095-1098.

[35]

Hebert JF, Burfeind KG, Malinoski D, Hutchens MP. Molecular mechanisms of rhabdomyolysis-induced kidney injury: from bench to bedside. Kidney Int Rep. 2023; 8(1): 17-29.

[36]

Sharif SI, Abouazra HA. Effect of intravenous ketamine administration on blood glucose levels in conscious rabbits. Am J Pharmacol Toxicol. 2009; 4(2): 38-45.

[37]

Parker LA, Krebs K, Pan PL, Varner KM, Hoddinott KL. Treatment and outcome following substantial ketamine overdose in a dog. Can Vet J. 2023; 64(3): 235-238.

[38]

Goldmann C, Ghofrani A, Hafemann B, et al. Combination anesthesia with ketamine and pentobarbital: a long-term porcine model. Res Exp Med. 1999; 199(1): 35-50.

RIGHTS & PERMISSIONS

2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

AI Summary AI Mindmap
PDF

79

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/