All procedures were approved by the Institutional Animal Care and Use Committee at Michigan State University. Adult male and female Long Evans rats (200-400g, n=10, 6 females, 4 males) rats were anesthetized with isoflurane (5% for induction; 2.5% for maintenance and surgery) and positioned in a stereotaxic frame. Stereotaxic injections of 5μl at each location contained AAV1-CaMKIIα - {EPG(Rat)X3Flag}: IRES: EGFP at a titer of 1013 GC/ml (n=5). Sham-control rats were injected with AAV-CaMKIIα-EGFP (n=5). See supporting information for DNA sequence detail. The microinjector was positioned at 4 location in the visual cortex: AP −7.3mm, ML 3.2mm; AP −7.3mm, ML −3.2mm; AP −5.4mm, ML 4mm; AP −5.4mm, ML −4mm. Two to four weeks after stereotaxic injections MRI measurements took place. The EPG sequence can be found in the gene bank: (GenBank:MH590650.1 ). For MRI the anesthesia was induced with 5% isoflurane, followed by a bolus injection of dexmedetomidine (0.05 mg/kg, sc; Dexdomitor®, Orion Pharma), after which isoflurane was discontinued, and a constant dexmedetomidine infusion (0.1 mg/kg/hr) was administered subcutaneously. During fMRI measurements, rats’ temperature was maintained at 37°C, and the breathing rate, partial oxygen saturation, and heart rate were continuously monitored.
Dexdomitor
Manufactured by Orion Pharma
Sourced in Finland, United States, Sweden
Dexdomitor is a veterinary prescription-only medication used as a sedative and analgesic in various animal species. It contains the active ingredient dexmedetomidine hydrochloride, which is an alpha-2 adrenoceptor agonist. Dexdomitor is administered by injection and primarily affects the central nervous system to induce a state of calm and relaxation.
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Lab products found in correlation
Ketanest, by Pfizer (4 mentions)
Antisedan, by Orion Pharma (3 mentions)
Tropicamide, by Sandoz (3 mentions)
Micron 3 retinal imaging microscope, by Phoenix Pharmaceuticals (3 mentions)
Torbugesic, by Zoetis (2 mentions)
Rnalater, by Thermo Fisher Scientific (2 mentions)
Aerrane isoflurane usp, by Baxter (1 mentions)
Zoletil, by Virbac (1 mentions)
Metacam, by Boehringer Ingelheim (1 mentions)
Fentanyl, by B. Braun (1 mentions)
Zoletil 100 vet, by Virbac (1 mentions)
Vetergesic vet, by Orion Pharma (1 mentions)
Streptocillin vet, by Boehringer Ingelheim (1 mentions)
Propovet multidose, by Orion Pharma (1 mentions)
Rimadyl vet, by Orion Pharma (1 mentions)
Phosphate buffered saline (pbs), by Lonza (1 mentions)
Isoflurane, by Baxter (1 mentions)
Omniscan, by GE Healthcare (1 mentions)
Butorphanol, by Zoetis (1 mentions)
Ketalar, by Pfizer (1 mentions)
25 protocols using dexdomitor
1
AAV-Mediated Gene Expression in Rat Visual Cortex
2
Dexmedetomidine Premedication in Canine Anesthesia
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All dogs were allowed to rest for 30 min before any medication. Dogs were randomly assigned to two treatment groups, premedication with DEX intramuscularly (Dexdomitor, Orion Pharma, Finland; 0.5 mg/mL) at 5 μg/kg (DEX5 group) or 10 μg/kg (DEX10 group). After the onset of sedation, an intravenous catheter was placed in the cephalic vein, and generalized anesthesia was induced with tiletamine-zolazepam (3 mg/kg, intravenously, Zoletil®, Virbac, France; Zoletil powder diluted with 5 mL of sterile water for injection; 50 mg/mL tiletamine and 50 mg/mL zolazepam) until loss of jaw tone. Then, endotracheal intubation was performed, and anesthesia was maintained with inhaled isoflurane (AERRANE isoflurane USP, Baxter, USA) in 100% oxygenation using a rebreathing circuit. Lactate Ringer’s solution (Lactated Ringer’s injection, GHP, Thailand) was intravenously administered at 10 mL/kg/h. All dogs were given analgesic drugs intravenously before surgery.
After the completion of the surgical procedure, all dogs were injected intravenously with 0.1 mg/kg of atipamezole hydrochloride (Antisedan, Orion Pharma, Finland; 5 mg/mL).
After the completion of the surgical procedure, all dogs were injected intravenously with 0.1 mg/kg of atipamezole hydrochloride (Antisedan, Orion Pharma, Finland; 5 mg/mL).
3
Anesthetic Protocol for Small Animal Procedures
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A complete blood count and biochemistry panel were performed in all cases. After conducting the clinical examination and taking into consideration the results of current blood tests, there were no contraindications to general anesthesia. Patients were premedicated intramuscularly with a mixture of dexmedetomidine (Dexdomitor, Orion Pharma) at a dose of 5mcg/kg with methadone (Comfortan, Dechra) at a dose of 0.2 mg/kg. Then, general anesthesia was induced with propofol (Scanofol, ScanVet) dosed according to the effect (usually approximately 1 mg/kg). The patient was intubated subsequently. After tracheotubus was sealed and connected to the Datex Ohmeda S5 inhalation anesthesia apparatus, anesthesia was maintained with isoflurane (Isovet, Piramal Healthcare). Intraoperative anesthesia was obtained by continuous infusion of fentanyl (Fentadon, Dechra) at 0.2 mcg/kg/min after previous bolus administration at 2.5 mcg/kg. Treatment of postoperative pain included administration of buprenorphine (Bupaq Multidose, Orion Pharma) at a dose of 20mcg/kg every 8h for the next 3 days, and meloxicam (Metacam, Boehringer Ingelheim), also for 3 days—initially at a dose of 0.2mg/kg, then 0.1mg/kg. In addition, on the first day, patients were given metamizole (Pyralgivet, Vet-Agro) at a dose of 25–50mg/kg every 8 hours.
4
Anesthesia and Vascular Access Protocol
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Animals were anesthetized with Isoflurane (5%; 1 L/min @ 50% O2 + 50% Atm.Air.), which was downregulated to 2–3% for insertion of tail vein catheter. The catheter was flushed with heparinized sterile isotonic saline (Leo Pharma; 5000 IE/a.e./mL; 0.33 mL Heparine per 100 mL Saline) to avoid clotting. Heart rate (HR) and SpO2 was monitorized (Nonin 2500A VET) and logged/visualized with custom-made scripts.2 A small bolus (“fast infusion”: ∼0.1 mL/10 s) of Dexmedetomidine (Dexdomitor; Orion Pharma; 0.1 mg/mL) was administered (Harvard Apparatus Pump 11, Pico Plus Elite) until a steep decrease in HR (∼20%; e.g., 375 to 300 bpm within 15 s) was observed. Regular infusion was continued (0.05 mg/kg/h. for the first hour; 0.15 mg/kg/h. hereafter) in combination with a downregulated isoflurane level (0.5%; 1 L/min) (Pawela et al., 2009 (link); Magnuson et al., 2014 (link)).
5
Tendon Injury Tissue Harvesting
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66 rats were anesthetized with a subcutaneous injection (0.5 mg/kg dexdomitor; Orion Pharma, Espoo, Finland; and Ketaminol, Intervet) while still suspended, and were taken down first when they were fully sedated. The corresponding unloaded controls were killed at the same time points. 58 rats were used for RNA extraction and harvested as follows during sedation. The skin was shaved and washed, and the healing tissue was dissected free of the surrounding soft tissue under aseptic conditions. Tissue harvest was timed to either 15 minutes or 3 hours after loading.
A midpart segment from the healing tendon (consisting of newly formed tissue only) was harvested, quickly rinsed in sodium chloride, snap-frozen in liquid nitrogen, and stored at -70°C until RNA extraction. The rats were thereafter euthanized with an overdose of pentobarbital sodium. The hind limbs were kept unloaded throughout the whole harvesting procedure. 8 rats were used for histology and harvested as follows, after euthanasia with carbon dioxide. The skin was shaved and the healing tissue was dissected free from the surrounding soft tissue. The healing Achilles tendon was taken out together with a small piece of the calf muscle (for orientation of the tissue) and placed on a silicone gel with two needles in purpose to keep the tendon straight.
A midpart segment from the healing tendon (consisting of newly formed tissue only) was harvested, quickly rinsed in sodium chloride, snap-frozen in liquid nitrogen, and stored at -70°C until RNA extraction. The rats were thereafter euthanized with an overdose of pentobarbital sodium. The hind limbs were kept unloaded throughout the whole harvesting procedure. 8 rats were used for histology and harvested as follows, after euthanasia with carbon dioxide. The skin was shaved and the healing tissue was dissected free from the surrounding soft tissue. The healing Achilles tendon was taken out together with a small piece of the calf muscle (for orientation of the tissue) and placed on a silicone gel with two needles in purpose to keep the tendon straight.
6
Anesthetic Protocol for Sheep Surgery
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Before surgery, the animals fasted for 24 h to prevent possible complications caused by regurgitation and tympany during the procedure and recovery. All sheep were premedicated with 4 mcg/kg IV Dexmedetomidine (Dexdomitor; Orion Pharma, Spain) and 0.2 mg/kg IV Morphine (Morphine 2%; B. Braun). Subsequently, animals were preoxygenated by mask at 5 L/min for a period of 5 min, followed by induction with 1 mg/kg IV Propofol (Propofol Lipide 1%; B. Braun) per minute until endotracheal intubation was performed. Moreover, esophageal catheterization was necessary to avoid ruminal tympany during anesthesia. Anesthetic maintenance was mask-induced and Sevoflurane (Sevoflo; Zoetis Belgium SA) was vaporized in 100% O2 (IsoTec 5; Datex-Ohmeda, United Kingdom) through a circular air system (S/5 Avance; Datex-Ohmeda anesthesia equipment, Finland).
Patient monitoring was achieved using a multiparametric vital signs monitor (S/5 Datex-Ohmeda) that consisted of an electrocardiogram, a pulsometer, a capnography, body temperature, and invasive blood pressure.
Patient monitoring was achieved using a multiparametric vital signs monitor (S/5 Datex-Ohmeda) that consisted of an electrocardiogram, a pulsometer, a capnography, body temperature, and invasive blood pressure.
7
Islet Transplantation in Brown Norway Rats
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Male Brown Norway rats weighting 250–300 g (Velaz, Czech Republic) were used as both islet donors and recipients. All protocols related to this study were approved by the Animal Care Committee of the Institute for Clinical and Experimental Medicine and the Ministry of Health of Czech Republic. Experimental animals were maintained according to the European Convention on Animal Care in a controlled temperature, humidity, and 12/12 light/dark regimen with free access to food pellets and water. All surgical procedures were performed under total anesthesia induced by intramuscularly injected mixture of ketamine (Narketan, Vétoquinol S.A., France; 1,5 mg/100 g), dexmedetomidine (Dexdomitor, Orion Pharma, Czech Republic; 0,005 mg/100 g) and butorphanol (Torbugesic Vet, Zoetis, Spain; 0,05 mg/100 g).
8
Anesthesia and Analgesia for Surgical Procedures
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All surgical interventions were carried out under general anaesthesia, including an intra‐muscular injection of dexmedetomidine (25–35 μg/kg i.m.; Dexdomitor; Orion Pharma Animal Health) and tiletamine‐zolazepam (50–70 mg/kg i.m.; Zoletil 100 Vet, Virbac) and maintained with intravenous infusion until effect with propofol (PropoVet multidose, Orion Pharma Animal Health) and Fentanyl (Fentanyl B. Braun). Carprofen (4 mg/kg, s.i.d., i.m., Rimadyl vet., Orion Pharma Animal Health) was given as a preemptive dose for up to 4 days with buprenorphine (0.03 mg/kg, i.m., Vetergesic vet, Orion Pharma Animal Health). Local anaesthesia was provided intra‐operatively via infiltrative injection with 1.8 ml of xylocaine (Xylocaine, Dental adrenalin, 20 mg/ml, and 12.5 μg/ml; Astra AB) per hemi‐mandible. Antibiotic prophylaxis was administered using bensylpenicillinprokain‐dihydrostreptomycin (25 mg/kg + 20 mg/kg, s.i.d, i.m.; Streptocillin vet., Boehringer Ingelheim Vetmedica). During anaesthesia, the animals were intubated and breathing was withheld by a ventilator. Vital parameters were monitored continuously (pulse oximetry, rectal temperature, blood pressure, CO2). All anaesthetics, analgesics, and other medications were administered in doses and intervals following standard veterinary practice and according to the study objectives.
9
Anesthetic Protocol for Rat Tracer Infusion
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In initial experiments, where tracers were infused into the brain by pumping, rats were anaesthetized by intraperitoneal injection of 2 ml/kg of KDA mix, consisting of a combination of ketamine (75 mg/kg, Nimatek, Eurovet), dexdomitor (0.5 mg/kg, Orion Pharma), and atropine (0.05 mg/kg, atropine sulphate, Eurovet) dissolved in PBS (Phosphate Buffered Saline, Lonza). Additional oxygen (99%) was administered via a nose cap to prevent hypoxia. As we experienced a more stable and adjustable level of anaesthesia with isoflurane, the remainder of the study was carried out with animals under anaesthesia with isoflurane (3% in O2) applied via an inhalation mask.
10
pH Capsule Implantation in Canine Gastric Mucosa
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On the morning of day 0, the morning meal was withheld and the dogs were sedated using butorphanol (0.2 mg/kg IV; Torbugesic 10 mg/mL injection; Fort Dodge Animal Health, FortDodge, Iowa) and dexmedetomidine (5‐10 μg/kg IV; Dexdomitor 0.5 mg/mL injection; Orion Pharma, Espoo, Finland). The Bravo pH capsules (Medtronic, Minneapolis, Minnesota) were placed utilizing digital radiology for assistance. Intragastric pH capsules were adhered to the dogs' gastric mucosa as described in other studies.11 After the procedure, the sedation was reversed with an equal volume of atipamezole (0.05‐0.1 mg/kg IM; Antisedan 5 mg/mL injection; Orion Pharma).
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