Aerrane

The experiment was terminated at 15 dpi. At this time, mice were euthanized by way of anaesthetic overdose (isoflurane gas inhalation; AErrane™ Baxter Corporation, Mississauga, ON, Canada) followed by exsanguination. A necropsy was performed immediately thereafter with focus on the gastrointestinal tract. Fresh samples of caecum and colon were collected for culture and nox PCR. The carcass was placed in 10% neutral buffered formalin for 24 h. and samples of ileum, colon, caecum, heart, lung, salivary gland, rectum, liver, spleen, kidney and stomach were processed routinely for histological analysis of 5 μm haematoxylin and eosin stained (H and E) sections by a board certified veterinary pathologist blinded to treatment group. For Experiment 1, the presence or absence of catarrhal inflammation and epithelial regeneration in the colon and caecum were recorded.

In vivo studies were performed under general anesthesia on 30 adult male SD rats classified into 3 time groups of 2, 5, and 8 weeks with 10 rats in each group subjected to implantation of gelatin-BVSM conduits. Anesthesia using the inhalational technique (AErrane, Baxter, Deerfield, IL, USA) was conducted prior to this test. After skin incision, muscles and fascia tissues were separated by blunt dissection, followed by transection of the right sciatic nerves into two segments, namely the distal and proximal segments. Both segments were secured with a single 9–0 nylon suture through the epineurium with the outer lumen of the conduits. The segments were attached at a depth of 2.5 mm, leaving a gap of 10 mm. 4–0 chromic gut sutures were used to re-approximate the layer of muscle, and the incision was closed using 2–0 silk sutures. The animals were housed in humidified rooms at 22 °C and 45% humidity with 12-h light cycles. Food and water were provided ad libitum. Clinically approved silicone rubber conduits were used as the control group.

Mice were pretreated with dexmedetomidine (50 μg/kg, i.p.) or vehicle at 30 min prior to 4-hour exposure to 1.3% isoflurane (in humidified 30% oxygen carrier gas) in a chamber partially submerged in a 37°C water bath [6 (link),8 (link)]. Isoflurane was delivered using a vaporizer (Aerrane, Baxter Healthcare, Deerfield, IL, USA). Concentrations of oxygen, carbon dioxide and isoflurane in the chamber were monitored using a monitor from Detex-Ohmeda (Louisville, KY, USA). A group of mice not exposed to isoflurane was included as an additional control. Core body temperature was measured with a rectal probe and maintained at 37 ± 0.5°C using a heating blanket.
In some experiments, animals were pretreated with the α₂ adrenoreceptor antagonist atipamezole (250 μg/kg, i.p.), the JAK2 inhibitor AG490 (15 mg/kg i.p; Sigma-Aldrich, St Louis, MO, USA) or the STAT3 inhibitor WP1066 (40 mg/kg i.p.; Sigma-Aldrich) at 30 min before dexmedetomidine injection.
Mice were anesthetized with sodium pentobarbital (50 mg/kg, i.p., n = 16) at the end of the 4-hour isoflurane exposure and blood samples were obtained from the femoral artery of animals for measurement of arterial blood gases and blood glucose. Animals were then allowed to recover from anesthesia. Cognition was assessed using a Morris water maze test at 2 w after isoflurane exposure.

This study was approved by the Animal Ethics Committee, Southern Laboratory Animal Facility, Faculty of Science, Prince of Songkla University (IACUC 2563-03-037). Forty-two male Wistar rats (Rattus norvegicus albinos) aged 3 to 4 months and weighing 350 to 400 g were used for the experiments. Prior to the experiment, all animals were raised and housed in a sterilized room with a photoperiod of 12/12 h beginning at 7 a.m., a controlled temperature of 25 °C, and humidity of 40 to 50%. The animals were randomly categorized into three groups: (1) control group (control), which received no treatment for a baseline on day 0 (n = 6); (2) corticotomy group (CO), which received only corticotomy-assisted orthodontic tooth movement (n = 18); and (3) corticotomy-assisted orthodontic tooth movement with ibuprofen intake group (CI) (n = 18) (Figure 1).
The rats underwent corticotomy and orthodontic appliance insertion operations under general anesthesia with anesthetic doses adjusted to the weight of each rat. A combination of 90 mg/kg of ketamine hydrochloride (Ketajex™, Baxter Pharmaceuticals India Private Limited, Ahmedabad, Gujarat, India) and 10 mg/kg of xylazine hydrochloride (X-Lazine, L.B.S. Laboratory Ltd., Bangkok, Thailand) was intraperitoneally injected to induce anesthesia after inhalation of 3% isoflurane (Aerrane, Baxter Healthcare Corporation, Deerfield, IL, USA).

To determine the origin of response failure of some molecules observed by telemetry, we recorded blood pressure coupled to heart rate change in anesthetized animal (2% inhaled isoflurane/O2, Aerrane, Baxter, France) using Powerlab system and LabChart software (Blood pressure module; ADInstruments Ltd, France). To this aim, a Millar Mikro-Tip^® pressure catheter is introduced in the carotid to record arterial blood pressure, and diastolic, systolic, and mean arterial blood pressures were calculated. In parallel, ECG was recorded using lead II Einthoven derivation using micro-needles to assess the heart rate changes induced by hemodynamic modifications. Parameters were measured in baseline conditions and after injection of Nitroprusside (2.0 mg k⁻¹ g ip, NaCl, 0.9%), Norepinephrine (2.5 mg kg⁻¹ ip, NaCl 0.9%) and Phenylephrine (2.5 mg kg⁻¹ ip, NaCl 0.9%). Parameters were measured and averaged during the maximal response, on fifteen complexes. The delta of heart rate and delta of mean BP was calculated. The Gain (Delta HR/Delta BP) was done and reflects cardiovascular adaptation during pharmacological dosing through baroreflex. All experiments were conducted between 7:00 am and 11:00 am.