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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

Maike Albrecht1, Julia Henke1*, Sabine Tacke2, Michael Markert3 and Brian Guth3

Author 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

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BMC Veterinary Research 2014, 10:198  doi:10.1186/s12917-014-0198-3

Published: 23 August 2014



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.


Differences were observed between anaesthesias with KX (301 min) lasting much longer than MMF (45 min) and ISO (43 min). HR in ISO ( = 404?±?25 bpm) increased during the time of surgical tolerance whereas a HR decrease was observed in KX ( = 255?±?26 bpm) and MMF ( = 209?±?24 bpm). In ISO (MAP during time of surgical tolerance: = 89?±?12.3 mmHg) and KX (MAP during wake-up period: = 84?±?8.5 mmHg) mild hypotensive values were observed, whereas blood pressure (BP) in MMF (MAP during time of surgical tolerance: = 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 ( = 445?±?20 bpm) during the wake-up period with ISO and an increase of PP ( = 59?±?8.5 mmHg) in MMF during the time of surgical tolerance.


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.

Rat; Anaesthesia; Isoflurane; Ketamine-xylazine; Medetomidine-midazolam-fentanyl; Telemetry; Heart rate; Blood pressure; Core body temperature