Rodent General Anesthesia Suitable for Measurement of Experimental Invasive Hemodynamics


  •   Filip Konecny


In cases of experimentally performed invasive rodent cardiovascular measurements, selected general anesthesia for a non-recovery procedure and its proper pain control plays a fundamental role in obtaining good data recordings. Rodent anesthesia is challenging for several reasons including high metabolic rate with elevated possibility of hypothermia and hypoglycemia during the procedure, large body surface area to adjust drug medication and anticipate drug clearance. In this review article, suitable analgesia, and anesthesia to collect rodent hemodynamics is discussed with examples of commonly used methods and anesthetic combinations to assess rodent hemodynamics. In case of injectable anesthesia, hemodynamic parameters should be measured when HR and mean arterial pressure (MAP) becomes stable. If re-injection is necessary, re-evaluation of HR and MAP is crucial for data integrity. Likewise, to safeguard data quality, longitudinal collection of HRs, HR variability, MAP and body temperature should be provided. For this reason, creation of a rodent hemodynamic anesthesia protocol might be necessary. In many cases, to refine surgical anesthetic protocol suitable for hemodynamic study, pilot experiments might be required to find the correct dose, and to probe for adequacy and duration of anesthesia, anticipating technical and procedural problems. Additionally, ensuring repeatability of the hemodynamic exam, selected experimental anesthetics should not be extensively metabolized. If metabolized, the effects on central and peripheral hemodynamics (HR, pre, afterload and contractility) should be well-known and documented.

Keywords: anesthesia monitoring, controlled mechanical ventilation, inhalation anesthesia, injectable, rodent general anesthesia


Sonner, J. M., Antognini, J. F., Dutton, R. C., Flood, P., Gray, A. T., Harris, R. A., Homanics, G. E., Kendig, J., Orser, B., Raines, D. E., Rampil, I. J., Trudell, J., Vissel, B., & Eger, E. I., 2nd (2003). Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesthesia and analgesia, 97(3), 718–740.

Eger, E. I., 2nd, Tang, M., Liao, M., Laster, M. J., Solt, K., Flood, P., Jenkins, A., Raines, D., Hendrickx, J. F., Shafer, S. L., Yasumasa, T., & Sonner, J. M. (2008). Inhaled anesthetics do not combine to produce synergistic effects regarding minimum alveolar anesthetic concentration in rats. Anesthesia and analgesia, 107(2), 479–485.

Urban BW, The Site of Anesthetic Action. Schwilden, H., & Schüttler, J. (2008). Target controlled anaesthetic drug dosing. Handbook of Experimental pharmacology, (182), 425–450.

Olsen R.W, DeLorey T.M. GABA Receptor Physiology and Pharmacology In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999.

Jevtović-Todorović, V., Todorović, S. M., Mennerick, S., Powell, S., Dikranian, K., Benshoff, N., Zorumski, C. F., & Olney, J. W. (1998). Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature medicine, 4(4), 460–463.

Mosley CA. Veterinary Anesthesia and Analgesia: in The Fifth Edition of Lumb and Jones. Edited by Kurt A. Grimm, Leigh A. Lamont, William J. Tranquilli, Stephen A. Greene and Sheilah A. Robertson. 2015 John Wiley & Sons, Inc. Published 2015 by John Wiley & Sons, Inc.

Rottman, J. N., Ni, G., & Brown, M. (2007). Echocardiographic evaluation of ventricular function in mice. Echocardiography (Mount Kisco, N.Y.), 24(1), 83–89.

Pachon, R. E., Scharf, B. A., Vatner, D. E., & Vatner, S. F. (2015). Best anesthetics for assessing left ventricular systolic function by echocardiography in mice. American journal of physiology. Heart and circulatory physiology, 308(12), H1525–H1529.

Liu, X., Rabin, P. L., Yuan, Y., Kumar, A., Vasallo, P., 3rd, Wong, J., Mitscher, G. A., Everett, T. H., 4th, & Chen, P. S. (2019). Effects of anesthetic and sedative agents on sympathetic nerve activity. Heart rhythm, 16(12), 1875–1882.

Aono, H., Hirakawa, M., Unruh, G. K., Kindscher, J. D., & Goto, H. (2001). Anesthetic induction agents, sympathetic nerve activity and baroreflex sensitivity: a study in rabbits comparing thiopental, propofol and etomidate. Acta medica Okayama, 55(4), 197–203.

Guedel A.E. Inhalation anesthesia, Ed 2, New York, 1951, Macmillan

Bhargava, A. K., Setlur, R., & Sreevastava, D. (2004). Correlation of bispectral index and Guedel's stages of ether anesthesia. Anesthesia and analgesia, 98(1).

Sotocinal, S. G., Sorge, R. E., Zaloum, A., Tuttle, A. H., Martin, L. J., Wieskopf, J. S., Mapplebeck, J. C., Wei, P., Zhan, S., Zhang, S., McDougall, J. J., King, O. D., & Mogil, J. S. (2011). The Rat Grimace Scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Molecular pain, 7, 55.

Matsumiya LC, Sorge RE, Sotocinal SG, et al. Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesics in laboratory mice. J Am Assoc Lab Anim Sci. 2012;51(1):42-49.

Kawai, S., Takagi, Y., Kaneko, S., & Kurosawa, T. (2011). Effect of three types of mixed anesthetic agents alternate to ketamine in mice. Experimental animals, 60(5), 481–487.

Crisler R., Johnston N.A, Sivula C., Budelsky CL; Chapter 4, Functional Anatomy and Physiology in The Laboratory Rat, Mark A. Suckow, ed., November 2019. pg.: 1180. Academic Press ISBN: 9780128143384.

Landi, M. S., Kreider, J. W., Lang, C. M., & Bullock, L. P. (1982). Effects of shipping on the immune function in mice. American journal of veterinary research, 43(9), 1654–1657.

Lofgren J.L.S, Foley P.L., Golledge H.D.R. Anesthesia, Analgesia, and Euthanasia. The Laboratory Rat. 2020:699-745. Editors: Suckow M, Hankenson FC, Wilson R, Foley P. Epub 2019 Nov 15.

Stokes, E. L., Flecknell, P. A., & Richardson, C. A. (2009). Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures. Laboratory animals, 43(2), 149–154.

Sinner B., Graf B.M. Ketamine. in Handb Exp Pharmacol. 2008;(182):313-33.

Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., Jr, & Gould, T. D. (2018). Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacological reviews, 70(3), 621–660.

Flecknell, P.A. Laboratory Animal Anaesthesia, 4 ed. Academic Press, Oxford, 2016.

Annetta, M. G., Iemma, D., Garisto, C., Tafani, C., & Proietti, R. (2005). Ketamine: new indications for an old drug. Current drug targets, 6(7), 789–794.

Kurdi, M. S., Theerth, K. A., & Deva, R. S. (2014). Ketamine: Current applications in anesthesia, pain, and critical care. Anesthesia, essays and research, 8(3), 283–290.

Janssen, B. J., De Celle, T., Debets, J. J., Brouns, A. E., Callahan, M. F., & Smith, T. L. (2004). Effects of anesthetics on systemic hemodynamics in mice. American journal of physiology. Heart and circulatory physiology, 287(4), H1618–H1624.

Wellington, D., Mikaelian, I., & Singer, L. (2013). Comparison of ketamine-xylazine and ketamine-dexmedetomidine anesthesia and intraperitoneal tolerance in rats. Journal of the American Association for Laboratory Animal Science : JAALAS, 52(4), 481–487.

Gaertner D.J., Hallman T.M., Hankenson F.C., Batchelder M.A. Anesthesia and Analgesia for Laboratory Rodents in: Fish R.E., Brown M.J., Danneman P.J., Karas A.Z., editors. Anesthesia and Analgesia in Laboratory Animals, 2nd Edition London: Academic Press, Elsevier; 2008. p. 239–98.

Cabral, A. D., Kapusta, D. R., Kenigs, V. A., & Varner, K. J. (1998). Central alpha2-receptor mechanisms contribute to enhanced renal responses during ketamine-xylazine anesthesia. The American journal of physiology, 275(6), R1867–R1874.

Wixson S.K., Smiler K.L., Chapter 9, Anesthesia and Analgesia in Rodents, Editor(s): Dennis F. Kohn, Sally K. Wixson, William J. White, G. John Benson: in American College of Laboratory Animal Medicine, Anesthesia and Analgesia in Laboratory Animals, Academic Press, 1997, p. 165-203.

Kanda, T., Gotoh, M., Makino, A., Furumoto, K., Shimizu, Y., Itoi, T., Maeta, N., & Furukawa, T. (2020). Effect of Different Doses of Atipamezole on Reversal of Medetomidine-Induced Tear-Flow Decrease in Rats. Veterinary sciences, 7(4), 197.

Olson, M. E., Vizzutti, D., Morck, D. W., & Cox, A. K. (1994). The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire, 58(4), 254–258.

Zuurbier, C. J., Koeman, A., Houten, S. M., Hollmann, M. W., & Florijn, W. J. (2014). Optimizing anesthetic regimen for surgery in mice through minimization of hemodynamic, metabolic, and inflammatory perturbations. Experimental biology and medicine (Maywood, N.J.), 239(6), 737–746.

Magalhães, A., Valentim, A., Venâncio, C., Pereira, M., Melo, P., Summavielle, T., & Antunes, L. (2017). Ketamine alone or combined with midazolam or dexmedetomidine does not affect anxiety-like behaviours and memory in adult Wistar rats. Laboratory animals, 51(2), 147–159.

Saha, D. C., Saha, A. C., Malik, G., Astiz, M. E., & Rackow, E. C. (2007). Comparison of cardiovascular effects of tiletamine-zolazepam, pentobarbital, and ketamine-xylazine in male rats. Journal of the American Association for Laboratory Animal Science : JAALAS, 46(2), 74–80.

Redfors, B., Shao, Y., & Omerovic, E. (2014). Influence of anesthetic agent, depth of anesthesia and body temperature on cardiovascular functional parameters in the rat. Laboratory animals, 48(1), 6–14.

Stoetzer, C., Reuter, S., Doll, T., Foadi, N., Wegner, F., & Leffler, A. (2016). Inhibition of the cardiac Na⁺ channel α-subunit Nav1.5 by propofol and dexmedetomidine. Naunyn-Schmiedeberg's archives of pharmacology, 389(3), 315–325.

Jin, Y. C., Kim, W., Ha, Y. M., Shin, I. W., Sohn, J. T., Kim, H. J., Seo, H. G., Lee, J. H., & Chang, K. C. (2009). Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo. Vascular pharmacology, 50(1-2), 71–77.

Alves, H. N., da Silva, A. L., Olsson, I. A., Orden, J. M., & Antunes, L. M. (2010). Anesthesia with intraperitoneal propofol, medetomidine, and fentanyl in rats. Journal of the American Association for Laboratory Animal Science : JAALAS, 49(4), 454–459.

Paasonen, J., Salo, R. A., Shatillo, A., Forsberg, M. M., Närväinen, J., Huttunen, J. K., & Gröhn, O. (2016). Comparison of seven different anesthesia protocols for nicotine pharmacologic magnetic resonance imaging in rat. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 26(3), 518–531.

Holland JR, Hosley H, Scharlau C, Carbone PP, Frei E 3rd, Brindley CO, Hall TC, Shnider BI, Gold GL, Lasagna L, Owens AH Jr, Miller SP. A controlled trial of urethane treatment in multiple myeloma. Blood. 1966 Mar.

Jong, W. M., Zuurbier, C. J., De Winter, R. J., Van Den Heuvel, D. A., Reitsma, P. H., Ten Cate, H., & Ince, C. (2002). Fentanyl-fluanisone-midazolam combination results in more stable hemodynamics than does urethane alpha-chloralose and 2,2,2-tribromoethanol in mice. Contemporary topics in laboratory animal science, 41(3), 28–32.

Zehendner, C. M., Luhmann, H. J., & Yang, J. W. (2013). A simple and novel method to monitor breathing and heart rate in awake and urethane-anesthetized newborn rodents. PloS one, 8(5), e62628.

Lau, C., Ranasinghe, M. G., Shiels, I., Keates, H., Pasloske, K., & Bellingham, M. C. (2013). Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan(®) in rats. Journal of veterinary pharmacology and therapeutics, 36(5), 516–520.

White, K. L., Paine, S., & Harris, J. (2017). A clinical evaluation of the pharmacokinetics and pharmacodynamics of intravenous alfaxalone in cyclodextrin in male and female rats following a loading dose and constant rate infusion. Veterinary anaesthesia and analgesia, 44(4), 865–875.

Jong, W. M., Zuurbier, C. J., De Winter, R. J., Van Den Heuvel, D. A., Reitsma, P. H., Ten Cate, H., & Ince, C. (2002). Fentanyl-fluanisone-midazolam combination results in more stable hemodynamics than does urethane alpha-chloralose and 2,2,2-tribromoethanol in mice. Contemporary topics in laboratory animal science, 41(3), 28–32.

Kitano, H., Kirsch, J. R., Hurn, P. D., & Murphy, S. J. (2007). Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 27(6), 1108–1128.

Yamakura, T., & Harris, R. A. (2000). Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol. Anesthesiology, 93(4), 1095–1101.

Mawhinney, L. J., de Rivero Vaccari, J. P., Alonso, O. F., Jimenez, C. A., Furones, C., Moreno, W. J., Lewis, M. C., Dietrich, W. D., & Bramlett, H. M. (2012). Isoflurane/nitrous oxide anesthesia induces increases in NMDA receptor subunit NR2B protein expression in the aged rat brain. Brain research, 1431, 23–34.

Constantinides, C., Mean, R., & Janssen, B. J. (2011). Effects of isoflurane anesthesia on the cardiovascular function of the C57BL/6 mouse. ILAR journal, 52(3), e21–e31.

Poon, Y. Y., Tsai, C. Y., Huang, Y. H., Wu, J., Chan, S., & Chan, J. (2021). Disproportional cardiovascular depressive effects of isoflurane: Serendipitous findings from a comprehensive re-visit in mice. Lab animal, 50(1), 26–31.

Feigl E. O. (1983). Coronary physiology. Physiological reviews, 63(1), 1–205.

Criado, A. B., & Gómez e Segura, I. A. (2003). Reduction of isoflurane MAC by fentanyl or remifentanil in rats. Veterinary anaesthesia and analgesia, 30(4), 250–256.

Santos, M., Kunkar, V., García-Iturralde, P., & Tendillo, F. J. (2004). Meloxicam, a specific COX-2 inhibitor, does not enhance the isoflurane minimum alveolar concentration reduction produced by morphine in the rat. Anesthesia and analgesia, 98(2).

Benito, J., Aguado, D., Abreu, M. B., García-Fernández, J., & Gómez de Segura, I. A. (2010). Remifentanil and cyclooxygenase inhibitors interactions in the minimum alveolar concentration of sevoflurane in the rat. British journal of anaesthesia, 105(6), 810–817.

Samad, T. A., Sapirstein, A., & Woolf, C. J. (2002). Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets. Trends in molecular medicine, 8(8), 390–396.

Vaughan C. W. (1998). Enhancement of opioid inhibition of GABAergic synaptic transmission by cyclo-oxygenase inhibitors in rat periaqueductal grey neurones. British journal of pharmacology, 123(8), 1479–1481.

Das U. N. (2005). Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?. The Journal of the Association of Physicians of India, 53, 623–627.

Gueye, P. N., Borron, S. W., Risède, P., Monier, C., Buneaux, F., Debray, M., & Baud, F. J. (2002). Buprenorphine and midazolam act in combination to depress respiration in rats. Toxicological sciences : an official journal of the Society of Toxicology, 65(1), 107–114.

Pattinson, K. T., Governo, R. J., MacIntosh, B. J., Russell, E. C., Corfield, D. R., Tracey, I., & Wise, R. G. (2009). Opioids depress cortical centers responsible for the volitional control of respiration. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29(25), 8177–8186.

Hall L.W., Clarke, K.W., Trim C.M. Veterinary anaesthesia, 10th ed. London; New York : W.B. Saunders, 2001.

Kaul, T. K., & Mittal, G. (2013). Mapleson's Breathing Systems. Indian journal of anaesthesia, 57(5), 507–515.

Wilding, L. A., Hampel, J. A., Khoury, B. M., Kang, S., Machado-Aranda, D., Raghavendran, K., & Nemzek, J. A. (2017). Benefits of 21% Oxygen Compared with 100% Oxygen for Delivery of Isoflurane to Mice (Mus musculus) and Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science : JAALAS, 56(2), 148–154.

Petersson, J., & Glenny, R. W. (2014). Gas exchange and ventilation-perfusion relationships in the lung. The European respiratory journal, 44(4), 1023–1041.

Edmark, L., Auner, U., Enlund, M., Ostberg, E., & Hedenstierna, G. (2011). Oxygen concentration and characteristics of progressive atelectasis formation during anaesthesia. Acta anaesthesiologica Scandinavica, 55(1), 75–81.

Harkema J.R.., Carey S.A., Wagner J.G., Dintzis S.M., Liggitt D., 2018. Nose, sinus, pharynx, and larynx. In: Treuting, P.M., Dintzis, S.M., Montine, K.S. (Eds.), Comparative Anatomy and Histology: A Mouse, Rat, and Human Atlas, second ed. Academic Press, London, pp. 89 e 114.

Konno, K., Itano, N., Ogawa, T., Hatakeyama, M., Shioya, K., & Kasai, N. (2014). New visible endotracheal intubation method using the endoscope system for mice inhalational anesthesia. The Journal of veterinary medical science, 76(6), 863–868.

Fox, M. S., Welch, I., Hobson, D., & Santyr, G. E. (2012). A novel intubation technique for minimally invasive longitudinal studies of rat lungs using hyperpolarized 3He magnetic resonance imaging. Laboratory animals, 46(4), 311–317.

Watanabe, A., Hashimoto, Y., Ochiai, E., Sato, A., & Kamei, K. (2009). A simple method for confirming correct endotracheal intubation in mice. Laboratory animals, 43(4), 399–401.

MacDonald, K. D., Chang, H. Y., & Mitzner, W. (2009). An improved simple method of mouse lung intubation. Journal of applied physiology (Bethesda, Md. : 1985), 106(3), 984–987.

Tarnavski, O., McMullen, J. R., Schinke, M., Nie, Q., Kong, S., & Izumo, S. (2004). Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies. Physiological genomics, 16(3), 349–360.

Loeven, A. M., Receno, C. N., Cunningham, C. M., & DeRuisseau, L. R. (2018). Arterial blood sampling in male CD-1 and C57BL/6J mice with 1% isoflurane is similar to awake mice. Journal of applied physiology (Bethesda, Md. : 1985), 125(6), 1749–1759.

Güldner, A., Kiss, T., Serpa Neto, A., Hemmes, S. N., Canet, J., Spieth, P. M., Rocco, P. R., Schultz, M. J., Pelosi, P., & Gama de Abreu, M. (2015). Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers. Anesthesiology, 123(3), 692–713.

Vieillard-Baron, A., Matthay, M., Teboul, J. L., Bein, T., Schultz, M., Magder, S., & Marini, J. J. (2016). Experts' opinion on management of hemodynamics in ARDS patients: focus on the effects of mechanical ventilation. Intensive care medicine, 42(5), 739–749.

Konecny, F. (2018) Right ventricular hemodynamics during controlled mechanical volume ventilation as compared to non-invasive ventilation. J Heart Res. 1(1):6-13.

Ghali, G. Z., & Ghali, M. (2021). Effects of isoflurane on arterial blood pressure, heart rate, and phrenic nerve discharge in the decerebrate rat. The International journal of neuroscience, 131(5), 489–503.

Tsukamoto, A., Niino, N., Sakamoto, M., Ohtani, R., & Inomata, T. (2018). The validity of anesthetic protocols for the surgical procedure of castration in rats. Experimental animals, 67(3), 329–336.

Cesarovic, N., Nicholls, F., Rettich, A., Kronen, P., Hässig, M., Jirkof, P., & Arras, M. (2010). Isoflurane and sevoflurane provide equally effective anaesthesia in laboratory mice. Laboratory animals, 44(4), 329–336.

Frost, K., Shah, M., Leung, V., & Pang, D. (2020). Aversion to Desflurane and Isoflurane in Sprague-Dawley Rats (Rattus Norvegicus). Animals : an open access journal from MDPI, 10(6), 950.

Lee, J. H., Kwon, O., & Kwon, J. Y. (2009). The effects of desflurane on delayed neuronal injury after transient forebrain ischemia in the rat. Korean journal of anesthesiology, 57(2), 195–202.


How to Cite
Konecny, F. (2021). Rodent General Anesthesia Suitable for Measurement of Experimental Invasive Hemodynamics. European Journal of Biology and Biotechnology, 2(4), 33–43.