title: Influence of repeated anaesthesia on physiological parameters in male Wistar rats: a telemetric study about isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl.
abstract: BACKGROUND
  This study evaluated the influence of repeated anaesthesia using isoflurane (ISO, 2-3 Vol%), ketamine-xylazine (KX, 100 mg·kg(-1) + 5 mg·kg(-1), i.m.) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg·kg(-1) + 2.0 mg·kg(-1) + 0.005 mg·kg(-1), i.m.) on heart rate (HR), arterial blood pressure (BP), body temperature (BT), duration of anaesthetic intervals and body weight (BW) in Wistar rats. Rats were instrumented with a telemetric system for the measurement of systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), pulse pressure (PP), HR and BT during induction, maintenance and recovery of anaesthesia. Each anaesthesia was performed six times within three weeks. KX was not antagonized, but ISO delivery was terminated 40 minutes after induction and MMF was reversed with atipamezole-flumazenil-naloxone (AFN, 0.75 mg·kg(-1) + 0.2 mg·kg(-1) + 0.12 mg·kg(-1), s.c.).
  
  
  RESULTS
  With repeated anaesthesia, ISO showed a decrease of HR and BP. A significant decrease of PP could be observed with repeated anaesthesia using MMF. HR and BP were not affected by repeated KX anaesthesia, but we noted a reduction of sleeping time and BW. Neither MMF nor ISO showed significant differences in the duration of anaesthetic intervals and BW. With KX we observed tissue necrosis at the injection site and surgical tolerance was not achieved in 25% of the anaesthesias performed.
  
  
  CONCLUSIONS
  HR, BP values, BT, duration of anaesthetic intervals and BW were affected differently by repeated anaesthesia performed with ISO, KX or MMF. ISO produced a reproducible anaesthesia, thereby being suitable for repeated use, but with a decrease of HR and BP throughout the six anaesthesias. The use of ISO in cases where these parameters should be unaffected is therefore not advised. The inability to produce a surgical tolerance, the reduction of sleeping time and BW, as well as the tissue necrosis are significant contraindications for a repeated use of KX. Only mild changes of BP were found with repeated MMF anaesthesia, so it seems suitable for serial use, unless the high BP and the low HR during the surgical plane of anaesthesia are undesirable for a special procedure.
authors.affiliation: Department of Nonclinical Drug Safety, Biological Laboratory Service, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach, Germany. maike.anika.albrecht@googlemail.com.
authors.forename: Maike
authors.initials: M
authors.lastname: Albrecht
authors.affiliation: Department of Nonclinical Drug Safety, Biological Laboratory Service, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach, Germany. julia.henke@boehringer-ingelheim.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Henke
authors.affiliation: Department of Veterinary Clinical Sciences, Clinic for Small Animals-Surgery, Justus-Liebig University, Frankfurter Str. 108, 35392, Giessen, Germany. Sabine.P.Tacke@vetmed.uni-giessen.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tacke
authors.affiliation: Department of Drug Discovery Support, General Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach, Germany. michael.markert@boehringer-ingelheim.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Markert
authors.affiliation: Department of Drug Discovery Support, General Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach, Germany. brian.guth@boehringer-ingelheim.com.
authors.forename: Brian
authors.initials: B
authors.lastname: Guth
mesh_terms: D000758:Anesthesia / Q000009:adverse effects / Q000662:veterinary*; D019162:Anesthetics, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007530:Isoflurane / Q000009:adverse effects / Q000494:pharmacology*; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013686:Telemetry / Q000662:veterinary; D014991:Xylazine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D019162:Anesthetics, Combined; D014991:Xylazine; D007649:Ketamine; D007530:Isoflurane; D020926:Medetomidine; D008874:Midazolam; D005283:Fentanyl