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      Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats

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          Abstract

          Background

          This study investigated effects on cardiovascular parameters during anaesthesia with isoflurane (ISO, 2–3 Vol%), ketamine-xylazine (KX, 100 mg•kg −1 + 5 mg•kg −1) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg•kg −1 + 2.0 mg•kg −1 + 0.005 mg•kg −1) in rats throughout induction, maintenance and recovery from anaesthesia. Rats were instrumented with a telemetric system for the measurement of systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), pulse pressure (PP), heart rate (HR) and core body temperature (BT). The parameters were continuously measured before, during and after each type of anaesthesia. Forty minutes after induction, ISO delivery was terminated and MMF was antagonized with atipamezole-flumazenil-naloxone (AFN, 0.75 mg•kg −1 + 0.2 mg•kg −1 + 0.12 mg•kg −1) whereas KX was not antagonized.

          Results

          Differences were observed between anaesthesias with KX (301 min) lasting much longer than MMF (45 min) and ISO (43 min). HR in ISO ( ˉx = 404 ± 25 bpm) increased during the time of surgical tolerance whereas a HR decrease was observed in KX ( ˉx = 255 ± 26 bpm) and MMF ( ˉx = 209 ± 24 bpm). In ISO (MAP during time of surgical tolerance: ˉx = 89 ± 12.3 mmHg) and KX (MAP during wake-up period: ˉx = 84 ± 8.5 mmHg) mild hypotensive values were observed, whereas blood pressure (BP) in MMF (MAP during time of surgical tolerance: ˉx = 138 ± 9.9 mmHg) increased. Despite keeping animals on a warming pad, a loss of BT of about 1°C was seen in all groups. Additionally, we observed a peaked increase of HR ( ˉx = 445 ± 20 bpm) during the wake-up period with ISO and an increase of PP ( ˉx = 59 ± 8.5 mmHg) in MMF during the time of surgical tolerance.

          Conclusion

          The anaesthesias influenced very differently the cardiovascular parameters measured in Wistar rats. ISO caused mild hypotension and increased HR whereas MMF produced a marked hypertension and a significant decrease of HR. The slightest alterations of BP, HR and BT were observed using KX, but the long wake-up and recovery period suggest the need for prolonged monitoring.

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          Most cited references42

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          Effects of anesthetics on systemic hemodynamics in mice.

          The aim of this study was to compare the systemic hemodynamic effects of four commonly used anesthetic regimens in mice that were chronically instrumented for direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and C57BL6 strains) were instrumented with a transit-time flow probe placed around the ascending aorta for CO measurement. An arterial catheter was inserted into the aorta 4 or 5 days later for blood pressure measurements. After full recovery, hemodynamic parameters including stroke volume, heart rate, CO, mean arterial pressure (MAP), and total peripheral resistance were measured with animals in the conscious state. General anesthesia was then induced in these mice using isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The doses and routes of administration of these agents were given as required for general surgical procedures in these animals. Compared with the values obtained for animals in the conscious resting state, MAP and CO decreased during all anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, -24 +/- 3%; CO, -5 +/- 7%; n = 15 mice) and greatest for K-X (MAP, -51 +/- 6%; CO, -37 +/- 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully antagonized by administration of the alpha(2)-receptor antagonist atipamezole (n = 8 mice). These results indicate that the anesthetic Iso has fewer systemic hemodynamic effects in mice than the nonvolatile anesthetics.
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            Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience.

            Ketamine alone or supplemented by diazepam or xylazine has been used and evaluated as an anaesthetic in a range of animals including snakes, tortoises, lizards, birds, ferrets, dogs, cats, pigs, sheep, goats, non-human primates, rabbits, guinea pigs, rats, mice and hamsters. Ketamine alone has severe limitations in most species, but in combination has proved valuable.
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              Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures.

              A structured literature review was carried out to assess recent trends in the administration of analgesics and anaesthetics to laboratory rats and mice undergoing surgical procedures. The ScienceDirect database was used to systematically identify studies published in peer-reviewed journals over two periods (2000-2001 and 2005-2006), 86 studies from each time period were included in the review. The total number of animals that underwent surgery, species used, type of procedure, anaesthetic regimen and analgesic administration were noted for each study. There was an increase in the reported administration of systemic analgesics from 10% in 2000-2001 to 20% in 2005-2006. Buprenorphine was the most commonly reported analgesic in both periods (2000-2001: 78%, 2005-2006: 35%) and reporting the use of non-steroidal anti-inflammatory drugs increased from 11% to 53%. There was also a change in reported anaesthetic practices, notably a decrease in the use of pentobarbital and an increase in the use of isoflurane and ketamine/xylazine. Although reported administration of analgesics has increased and there has been some refinement in the selection of anaesthetic agents used, the findings of this review suggest that there is still significant scope for improvement with respect to the perioperative care of laboratory rodents.
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                Author and article information

                Contributors
                Journal
                BMC Vet Res
                BMC Vet. Res
                BMC Veterinary Research
                BioMed Central
                1746-6148
                2014
                23 August 2014
                : 10
                : 198
                Affiliations
                [1 ]Department of Nonclinical Drug Safety, Biological Laboratory Service, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach, 88397, Germany
                [2 ]Department of Veterinary Clinical Sciences, Clinic for Small Animals-Surgery, Justus-Liebig University, Frankfurter Str. 108, Giessen, 35392, Germany
                [3 ]Department of Drug Discovery Support, General Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, Biberach, 88397, Germany
                Article
                s12917-014-0198-3
                10.1186/s12917-014-0198-3
                4363998
                25149627
                5ab5e568-41bc-47e0-a7d4-a7c28f1b86ca
                Copyright © 2014 Albrecht et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 April 2014
                : 15 August 2014
                Categories
                Research Article

                Veterinary medicine
                rat,anaesthesia,isoflurane,ketamine-xylazine,medetomidine-midazolam-fentanyl,telemetry,heart rate,blood pressure,core body temperature

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