Abstract
Chemical immobilization is necessary for the physiological study of large wild animals. However, the immobilizing drugs can adversely affect the cardiovascular and respiratory systems, yielding data that do not accurately represent the normal, resting state. We hypothesize that these adverse effects can be ameliorated by reversing the immobilizing agent while holding the animal under general anaesthesia. We used habituated sheep Ovis aries (N = 5, 46.9 ± 5.3 kg body mass, mean ± SEM) and goats Capra hircus (N = 4, 27.7 ± 2.8 kg) as ungulate models for large wild animals, and measured their cardiorespiratory function under three conditions: (1) mild sedation (midazolam), as a proxy for the normal resting state, (2) immobilization (etorphine and azaperone), and (3) general anaesthesia (propofol) followed by etorphine antagonism (naltrexone). Cardiac output for both sheep and goats remained unchanged across the three conditions (overall means of 6.2 ± 0.9 and 3.3 ± 0.3 L min−1, respectively). For both sheep and goats, systemic and pulmonary mean arterial pressures were significantly altered from initial midazolam levels when administered etorphine + azaperone, but those arterial pressures were restored upon transition to propofol anaesthesia and antagonism of the etorphine. Under etorphine + azaperone, minute ventilation decreased in the sheep, though this decrease was corrected under propofol, while the minute ventilation in the goats remained unchanged throughout. Under etorphine + azaperone, both sheep and goats displayed arterial blood hypoxia and hypercapnia (relative to midazolam levels), which failed to completely recover under propofol, indicating that more time might be needed for the blood gases to be adequately restored. Nonetheless, many of the confounding cardiorespiratory effects of etorphine were ameliorated when it was antagonized with naltrexone while the animal was held under propofol, indicating that this procedure can largely restore the cardiovascular and respiratory systems closer to a normal, resting state.
Similar content being viewed by others
References
Alford BT, Burkhart RL, Johnson WP (1974) Etorphine and diprenorphine as immobilizing and reversing agents in captive and free-ranging mammals. J Am Vet Med Assoc 164(7):702–705
American Society of Anesthesiologists (2004) Continuum of depth of sedation: definition of general anesthesia and levels of sedation/analgesia. Asahq. http://www.asahq.org/quality-and-practice-management/standards-guidelines-and-related-resources. Accessed 23 Aug 2018
Atkinson MW, Hull B, Gandolf AR, Blumer ES (2002) Repeated chemical immobilization of a captive greater one-horned rhinoceros (Rhinoceros unicornis), using combinations of etorphine, detomidine, and ketamine. J Zoo Wildl Med 33(2):157–162
Barenbrug AWT (1974) Psychrometry and psychrometric charts. Cape and Transvaal Printers Ltd, Cape Town
Barke KE, Hough LB (1993) Opiates, mast cells and histamine release. Life Sci 53(18):1391–1399
Beker A, Gipson TA, Puchala R, Askar AR, Tesfai K, Detweiler GD, Asmare A, Goetsch AL (2010) Energy expenditure and activity of different types of small ruminants grazing varying pastures in the summer. J Appl Anim Res 37(1):1–14
Boesch JM, Boulanger JR, Curtis PD, Erb HN, Ludders JW, Kraus MS, Gleed RD (2011) Biochemical variables in free-ranging white-tailed deer (Odocoileus virginianus) after chemical immobilization in clover traps or via ground-darting. J Zoo Wildl Med 42(1):18–28
Boom M, Niesters M, Sarton E, Aarts L, Smith W, Dahan T A (2012) Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des 18(37):5994–6004
Brøndum E, Hasenkam JM, Secher NH, Bertelsen MF, Grøndahl C, Petersen KK, Buhl R, Aalkjaer C, Baandrup U, Nygaard H (2009) Jugular venous pooling during lowering of the head affects blood pressure of the anesthetized giraffe. Am J Physiol Regul Integr Comp Physiol 297(4):R1058–R1065
Buss PE, Meltzer DGA (2001) Changes in respiratory function following the intramuscular administration of etorphine to boer goats (Capra hircus). J S Afr Vet Assoc 72(3):137–142
Buss PE, Miller M, Fuller A, Haw A, Wanty R, Olea-Popelka F, Meyer LCR (2016) Cardiovascular effects of etorphine, azaperone, and butorphanol combinations in chemically immobilized captive white rhinoceros (Ceratotherium simum). J Zoo Wildl Med 47(3):834–843
Cabral AMS, da Costa CP, Huggins SE (1980) Cardiac output in the three-toed sloth, Bradypus tridactylus. Comp Biochem Physiol Part A Physiol 67(3):527–530
Chahl LA (1996) Opioids-mechanisms of action. Aust Prescr 19(3):63–65
Clarke K (1969) Effect of azaperone on the blood pressure and pulmonary ventilation in pigs. Vet Rec 85:649–651
Curran-Everett D (2006) A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equation. Adv Physiol Educ 30(2):58–62
Daskalopoulos NT, Laubie M, Schmitt H (1975) Localization of the central sympatho-inhibitory effect of a narcotic analgesic agent, fentanyl, in cats. Eur J Pharmacol 33(1):91–97
Egermann M, Goldhahn J, Holz R, Schneider E, Lill CA (2008) A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare. Lab Anim 42(4):453–464
Fegler G (1954) Measurement of cardiac output in anaesthetized animals by a thermo-dilution method. Exp Physiol 39(3):153–164
Fernández C, López MC, Lachica M (2012) Heat production determined by the RQ and CN methods, fasting heat production and effect of the energy intake on substrates oxidation of indigenous Manchega sheep. Anim Feed Sci Technol 178(1–2):115–119
Gautret B, Schmitt H (1984) Cardiac slowing induced by peripheral κ-opiate receptor stimulation in rats. Eur J Pharmacol 102(1):159–163
Gautret B, Schmitt H (1985) Multiple sites for the cardiovascular actions of fentanyl in rats. J Cardiovasc Pharmacol 7(4):649–652
Goodman NW, Black AMS, Carter JA (1987) Some ventilatory effects of propofol as sole anaesthetic agent. Br J Anaesth 59(12):1497–1503
Greene SA (2002) Veterinary anesthesia and pain management secrets. Elsevier Health Sciences, London
Greth A, Vassart M, Anagariyah S (1993) Chemical immobilization in gazelles (Gazella sp.) with fentanyl and azaperone. Afr J Ecol 31(1):66–74
Grossmann M, Abiose A, Tangphao O, Blaschke TF, Hoffman BB (1996) Morphine-induced venodilation in humans. Clin Pharmacol Ther 60(5):554–560
Hakim T, Grunstein M, Michel R (1992) Opiate action in the pulmonary circulation. Pulm Pharmacol 5(3):159–165
Hattingh J, Knox C, Raath J, Keet D (1994) Arterial blood pressure in anaesthetized African elephants. S Afr J Wildl Res 24(1–2):15–17
Heard DJ, Kollias GV, Buss D, Caligiuri R, Coniglario J (1990) Comparative cardiovascular effects of intravenous etorphine and carfentanil in domestic goats. J Zoo Wildl Med 21(2):166–170
Hoka S, Yamaura K, Takenaka T, Takahashi S (1998) Propofol-induced increase in vascular capacitance is due to inhibition of sympathetic vasoconstrictive activity. J Am Soc Anaesth 89(6):1495–1500
Holt J, Rhode E, Kines H (1968) Ventricular volumes and body weight in mammals. Am J Physiol 215(3):704–715
Jackson P, Cockcroft P (2008) Clinical examination of farm animals. Wiley, Malden
Laubie M, Schmitt H, Canellas J, Roquebert J, Demichel P (1974) Centrally mediated bradycardia and hypotension induced by narcotic analgesics: dextromoramide and fentanyl. Eur J Pharmacol 28(1):66–75
Lees P, Serrano L (1976) Effects of azaperone on cardiovascular and respiratory functions in the horse. Br J Pharmacol 56(3):263–269
Lenaerts I, Driesen RB, Blanco NH, Holemans P, Heidbüchel H, Janssens S, Balligand J-L, Sipido KR, Willems R (2013) Role of nitric oxide and oxidative stress in a sheep model of persistent atrial fibrillation. Europace 15(5):754–760
Lowenstein E, Whiting RB, Bittar DA, Sanders CA, Powell WJ (1972) Local and neurally mediated effects of morphine on skeletal muscle vascular resistance. J Pharmacol Exp Ther 180(2):359–367
Lynch GM, Hanson JA (1981) Use of etorphine to immobilize moose. J Wildl Manag 45(4):981–985
MacKenzie G, Snow D (1977) An evaluation of chemical restraining agents in the horse. Vet Rec 101(2):30–33
Madan AK, Korde JP, Das AK, Rastogi SK (2010) Propofol-induced electroencephalographic, electrocardiographic and spirometric changes in goats. Vet Arch 80(1):27–39
Mansour E, Capone R, Mason DT, Amsterdam EA, Zelis R (1970) The mechanism of morphine-induced peripheral arteriolar dilation—central nervous sympatholysis. Am J Cardiol 26(6):648
Marano G, Grigioni M, Tiburzi F, Vergari A, Zanghi F (1996) Effects of isoflurane on cardiovascular system and sympathovagal balance in New Zealand white rabbits. J Cardiovasc Pharmacol 28(4):513–518
McQueen DS (1983) Opioid peptide interactions with respiratory and circulatory systems. Br Med Bull 39(1):77–82
Meyer LCR, Hetem RS, Fick LG, Mitchell D, Fuller A (2010) Effects of serotonin agonists and doxapram on respiratory depression and hypoxemia in etorphine-immobilized impala (Aepyceros melampus). J Wildl Dis 46(2):514–524
Meyer LCR, Hetem RS, Mitchell D, Fuller A (2015) Hypoxia following etorphine administration in goats (Capra hircus) results more from pulmonary hypertension than from hypoventilation. BMC Vet Res 11(1):1
Mir SA, Nazki AR, Raina R (2000) Comparative electrocardiographic studies, and differing effects of pentazocine on ECG, heart and respiratory rates in young sheep and goats. Small Rumin Res 37(1):13–17
Mirenda J, Broyles G (1995) Propofol as used for sedation in the ICU. Chest J 108(2):539–548
Muzi M, Berens RA, Kampine JP, Ebert TJ (1992) Venodilation contributes to propofol-mediated hypotension in humans. Anesth Analg 74(6):877–883
Nieuwenhuijs D, Sarton E, Teppema LJ, Kruyt E, Olievier I, van Kleef J, Dahan A (2001) Respiratory sites of action of propofol: absence of depression of peripheral chemoreflex loop by low-dose propofol. J Am Soc Anaesth 95(4):889–895
O’Keefe RJ, Domalik-Wawrzynski L, Guerrero JL, Rosow CE, Lowenstein E, Powell WJ (1987) Local and neurally mediated effects of sufentanil on canine skeletal muscle vascular resistance. J Pharmacol Exp Ther 242(2):699–706
Ozeki LM, Fahlman Å, Stenhouse G, Arnemo JM, Caulkett N (2014) Evaluation of the accuracy of different methods of monitoring body temperature in anesthetized brown bears (Ursus arctos). J Zoo Wildl Med 45(4):819–824
Paintal AS (1969) Mechanism of stimulation of type J pulmonary receptors. J Physiol 203(3):511–532
Pattinson KTS (2008) Opioids and the control of respiration. Br J Anaesth 100(6):747–758
Perrin KL, Denwood MJ, Grøndahl C, Nissen P, Bertelsen MF (2015) Comparison of etorphine–acepromazine and medetomidine–ketamine anesthesia in captive impala (Aepyceros melampus). J Zoo Wildl Med 46(4):870–879
Presnell KR, Presidente PJA, Rapley WA (1973) Combination of etorphine and xylazine in captive white-tailed deer: I. sedative and immobilization properties. J Wildl Dis 9(4):336–341
Price EO (1999) Behavioral development in animals undergoing domestication. Appl Anim Behav Sci 65(3):245–271
Radcliffe RW, Morkel P, Jago M, Taft AA, Du Preez P, Miller MA, Candra D, Nydam DV, Barry JS, Gleed RD (2014) Pulmonary dead space in free-ranging immobilized black rhinoceroses (Diceros bicornis) in Namibia. J Zoo Wildl Med 45(2):263–271
Rey B, Fuller A, Hetem RS, Lease HM, Mitchell D, Meyer LCR (2016) Microchip transponder thermometry for monitoring core body temperature of antelope during capture. J Therm Biol 55:47–53
Rosa G, Conti G, Orsi P, D’Alessandro F, Rosa IL, Giugno GD, Gasparetto A (1992) Effects of low-dose propofol administration on central respiratory drive, gas exchanges and respiratory pattern. Acta Anaesthesiol Scand 36(2):128–131
Roussel YE, Patenaude R (1975) Some physiological effects of M99 etorphine on immobilized free-ranging moose. J Wildl Manag 39(3):634–636
Runciman WB, Mather LE, Selby DG (1990) Cardiovascular effects of propofol and of thiopentone anaesthesia in the sheep. Br J Anaesth 65(3):353–359
Seymour RS, Blaylock AJ (2000) The principle of Laplace and scaling of ventricular wall stress and blood pressure in mammals and birds. Physiol Biochem Zool 73(4):389–405
Shaw M, Carpenter J, Leith D (1995) Complications with the use of carfentanil citrate and xylazine hydrochloride to immobilize domestic horses. J Am Vet Med Assoc 206(6):833–836
Shook JE, Watkins WD, Camporesi EM (1990) Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. Am Rev Respir Dis 142(4):895–909
Sinclair MD (2003) A review of the physiological effects of α2-agonists related to the clinical use of medetomidine in small animal practice. Can Vet J 44(11):885
Snelling EP, Seymour RS, Green JEF, Meyer LCR, Fuller A, Haw A, Mitchell D, Farrell AP, Costello M-A, Izwan A (2016) A structure-function analysis of the left ventricle. J Appl Physiol 121(4):900–909
Splinter WM, MacNeill HB, Menard EA, Rhine EJ, Roberts DJ, Gould MH (1995) Midazolam reduces vomiting after tonsillectomy in children. Can J Anaesth 42(3):201–203
Springer A, Razafimanantsoa L, Fichtel C, Kappeler PM (2015) Comparison of three short-term immobilization regimes in wild Verreaux’s sifakas (Propithecus verreauxi): ketamine–xylazine, ketamine–xylazine–atropine, and tiletamine–zolazepam. J Zoo Wildl Med 46(3):482–490
Stahl WR (1967) Scaling of respiratory variables in mammals. J Appl Physiol 22(3):453–460
Stegmann GF, Bester L (2001) Sedative-hypnotic effects of midazolam in goats after intravenous and intramuscular administration. Vet Anaesth Analg 28(1):49–55
Trapani GM, Altomare C, Sanna E, Biggio G, Liso G (2000) Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem 7(2):249–271
Upton RN, Martinez AM, Grant C (2009) Comparison of the sedative properties of CNS 7056, midazolam, and propofol in sheep. Br J Anaesth 103(6):848–857
Vahle-Hinz C, Detsch O (2002) What can in vivo electrophysiology in animal models tell us about mechanisms of anaesthesia? Br J Anaesth 89(1):123–142
Wenger S, Boardman W, Buss P, Govender D, Foggin C (2007) The cardiopulmonary effects of etorphine, azaperone, detomidine, and butorphanol in field-anesthetized white rhinoceroses (Ceratotherium simum). J Zoo Wildl Med 38(3):380–387
Willette RN, Sapru HN (1982) Pulmonary opiate receptor activation evokes a cardiorespiratory reflex. Eur J Pharmacol 78(1):61–70
Willette RN, Krieger AJ, Sapru HN (1982) Blood pressure and splanchnic nerve activity are reduced by a vagally mediated opioid action. J Cardiovasc Pharmacol 4(6):1006–1011
Woolf A (1970) Immobilization of captive and free-ranging white-tailed deer (Odocoileus virginianus) with etorphine hydrochloride. J Am Vet Med Assoc 157(5):636–640
Woolf A, Hays HR, Allen WB, Swart J (1973) Immobilization of wild ungulates with etorphine HC1. J Zoo A Med 4(4):16–19
Acknowledgements
The authors acknowledge the expertise and contribution made by the academics, technicians, and volunteers at the School of Physiology, and the Central Animal Service, at the University of the Witwatersrand. We thank especially David Gray, Zipho Zwane, Robyn Hetem, Benjamin Rey, Nico Douths, Peter Kamerman, Richard McFarland, Hilary Lease, Peter Buss, Michelle Miller, Tapiwa Chinaka, and W. Maartin Strauss. We also thank Tobias Wang of Aarhus University, and one anonymous reviewer, for providing valuable feedback on the manuscript. This research was supported by an Australian Research Council Discovery Project Award to R. S. Seymour, S. K. Maloney, and A. P. Farrell (DP-120102081). E. P. Snelling holds a South African Claude Leon Foundation Postdoctoral Fellowship. A. P. Farrell holds a Canada Research Chair and is supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada.
Author information
Authors and Affiliations
Contributions
EPS, RSS, LCRM, AF, AH, DM, APF, M-AC, and SKM: conception and design of research; EPS, RSS, LCRM, AF, AH, DM, APF, M-AC, and SKM: performed experiments; AI: analysed data; AI, EPS, RSS, LCRM, and SKM: interpreted results of experiments; AI: prepared figures; AI, EPS, RSS, and SKM: drafted the manuscript; AI, EPS, RSS, AF, LCRM, APF, and SKM: edited and revised the manuscript; AI, EPS, RSS, LCRM, AF, AH, DM, APF, M-AC, and SKM: approved the final version of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
Additional information
Communicated by I. D. Hume.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Izwan, A., Snelling, E.P., Seymour, R.S. et al. Ameliorating the adverse cardiorespiratory effects of chemical immobilization by inducing general anaesthesia in sheep and goats: implications for physiological studies of large wild mammals. J Comp Physiol B 188, 991–1003 (2018). https://doi.org/10.1007/s00360-018-1184-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00360-018-1184-z