title: Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats.
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 ([Formula: see text] = 404 ± 25 bpm) increased during the time of surgical tolerance whereas a HR decrease was observed in KX ([Formula: see text] = 255 ± 26 bpm) and MMF ([Formula: see text] = 209 ± 24 bpm). In ISO (MAP during time of surgical tolerance: [Formula: see text] = 89 ± 12.3 mmHg) and KX (MAP during wake-up period: [Formula: see text] = 84 ± 8.5 mmHg) mild hypotensive values were observed, whereas blood pressure (BP) in MMF (MAP during time of surgical tolerance: [Formula: see text] = 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 ([Formula: see text] = 445 ± 20 bpm) during the wake-up period with ISO and an increase of PP ([Formula: see text] = 59 ± 8.5 mmHg) in MMF during the time of surgical tolerance.
  
  
  CONCLUSIONS
  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.
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@boehringer-ingelheim.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: D000762:Anesthesia Recovery Period; D019162:Anesthetics, Combined / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology*; D008991:Monitoring, Physiologic; D051381:Rats; D017208:Rats, Wistar; D013686:Telemetry; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019162:Anesthetics, Combined; D014991:Xylazine; D007649:Ketamine; D007530:Isoflurane; D020926:Medetomidine; D008874:Midazolam; D005283:Fentanyl