| 1. |
- Askar, Raad, et al.
(author)
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Bioavailability of subcutaneous and intramuscular administrated buprenorphine in New Zealand White rabbits
- 2020
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In: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 16:1
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Journal article (peer-reviewed)abstract
- BackgroundBuprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01–0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (mean ± SD body weight 3.1 ± 0.3 kg) were administered 0.05 mg/kg buprenorphine by the IV, IM and SC routes and 0.1 mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8 h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS.ResultsThe area under the time concentration curve (AUC0-t) was lower after SC (398 ± 155 ng/mL/min) than IM (696 ± 168 ng/mL/min, p < 0.001) and IV (789 ± 189 ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 ± 1.4 ng/mL) than after IM (11 ± 3.2 ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 ± 19%) than after IM (95 ± 21%) administration (p = 0.006). The elimination half-life was longer after SC (260 ± 120 min) than after IM (148 ± 26 min, p = 0.002) as well as IV (139 ± 33 min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1 mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p = 0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 ± 14%, p = 0.6), whereas it increased in the males (71 ± 23%, p = 0.008).ConclusionsThe lower bioavailability of 0.05 mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability.
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| 2. |
- Aulin, C., et al.
(author)
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Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits
- 2013
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In: Laboratory Animals. - : SAGE Publications. - 0023-6772 .- 1758-1117. ; 47:1, s. 58-65
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Journal article (peer-reviewed)abstract
- Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint.
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| 3. |
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| 4. |
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| 5. |
- Aulin, Cecilia, et al.
(author)
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In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis
- 2011
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 5:8, s. E188-E196
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Journal article (peer-reviewed)abstract
- The present work describes the feasibility of a cross-linkable injectable hyaluronan hydrogel for cartilage repair. The hydrogel used is a two-component system based on aldehyde-modified hyaluronan and hydrazide-modified polyvinyl alcohol, which are rapidly cross-linked in situ upon mixing. The in vitro study showed that chondrocytes and mesenchymal cells cultured in the gel form cartilage-like tissue, rich in glycosaminoglycans, collagen type II and aggrecan. In a rabbit animal model the injection of the hydrogel improved the healing of a full-thickness cartilage defect created in the knee as compared to non-treated controls. This rabbit study showed that the regenerated cartilage defects stained more intensely for type II collagen upon treatment with the hydrogel. The hyaluronan-based hydrogel may be used as a delivery vehicle for both growth factors and/or cells for cartilage repair. The in vivo study also indicated that the hydrogel alone has a beneficial effect on cartilage regeneration.
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| 6. |
- Essner, Ann, 1971-
(author)
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On assessment methods related to pain in dogs with osteoarthritis
- 2018
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Doctoral thesis (other academic/artistic)abstract
- There is a need of valid and reliable assessment methods that are clinically applicable in canine rehabilitation practice. The aim of this thesis was to psychometrically evaluate measurement properties in assessment methods related to pain in naturally occurring canine osteoarthritis. Assessment methods developed for heart rate variability analysis, i.e. Polar heart rate monitor, and owner-reported perceptions of pain severity and pain interference with functionality, i.e. Canine Brief Pain Inventory, were tested.Methods: Four observational studies were conducted. Study I was a cross-sectional study consisting of two groups of consecutively recruited dogs. The Canine Brief Pain Inventory was administered to owners of dogs with naturally occurring osteoarthritis (n=61) and clinically sound dogs (n=21). Study II was a descriptive and correlative cross-sectional study based on the same sample of dogs with osteoarthritis (n=71), assessing chronic pain behavior and associations between explanatory variables and chronic pain behavior. Study III and IV were correlative studies, assessing Polar heart rate monitor measuring interbeat intervals and time- and frequency-based heart rate variability parameters, compared to simultaneously recorded electrocardiogram in dogs (n=11).Results: High internal consistencies and ability to discriminate sound dogs from osteoarthritis dogs were found. The hypothesis of the presented two-factor structure of the Canine Brief Pain Inventory was rejected. Owners reported higher proportions of chronic pain behavior in items targeting physical activities, e.g. getting up, moving after rest and moving after major exercise. A minor proportion of dogs with osteoarthritis showed no owner-perceived behavioural signs of chronic pain. Owner observations were not associated with ongoing antiinflammatory medications. In Study III and IV, 595 errors (12.3%) were identified in Polar data. The number of errors were unequally distributed among the dogs. Interbeat intervals and heart rate variability parameters from electrocardiogram and Polar were strongly associated. Standard error of measurements were high among some heart rate variability parameters in Polar and electrocardiogram.In conclusion, this thesis contributes to our knowledge about assessment methods related to diverse components of pain in dogs with osteoarthritis, allowing improved pain management in clinical practice.
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| 7. |
- Grims, Charlotta, et al.
(author)
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Are female mice dehydrated during peak lactation? Effect of water and gel supplement on hydration parameters and water consumption in two strains of mice
- 2021
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In: Scandinavian Journal of Laboratory Animal Science. - 0901-3393. ; 47:1, s. 16-24
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Journal article (peer-reviewed)abstract
- Mice (Mus musculus) have a high basal rate of metabolism which increases during pregnancy and lactation. During peak lactation, water intake amounts to up to 65 % of the bodyweight per day. Providing water in a bottle may pose a restriction of water intake and lead to dehydration during periods of high demand, such as peak lactation. To establish if female mice are able to sustain a physiological hydration status during peak lactation, a completely randomized facto-rial design study was conducted with 12 RjOrl:SWISS (SWISS) and 12 C57BL/6JRj (B6) six-week old female mice in breeding. Female mice were randomly assigned to one of three groups with different watering alternatives: water bottle (Standard, n=6); water bottle + sachet with 98 % water gel (Gel, n=6); or water bottle + water bowl (Bowl, n=6). Non-mated females, pro-vided with water bottles, served as controls (n=6). Hydration parameters [total protein (TP), hemoglobin, hematocrit, serum osmolality (Osmol), blood urea nitrogen (BUN)] and magnesium were measured in blood before mating (Pre) and during peak lactation (Peak), and at the same time points in controls. Water bottles were weighed during lactation and body weights of females and litters recorded at weaning. Data were analyzed by parametric or non-paramet-ric methods to evaluate effects of strain, group and time point. The hydration parameters and magnesium were mostly within normal ranges in all animals at Pre and Peak. TP was lower at Peak in all lactating groups compared to Controls and to Pre (p<0.01). Mice in group Bowl con-sumed 54 % less bottle water compared with Gel and Standard (p<0.001), had 34 % lower levels of BUN than Standard and Control (p<0.01) and 5 % lower serum osmolality at Peak than Pre (p<0.01). Conclusion: Female mice are not dehydrated at peak lactation. However, they prefer to drink, and seemingly drink more water, from a bowl than from a bottle.
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| 8. |
- Hedenqvist, Patricia
(author)
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Anaesthesia and analgesia for surgery in rabbits and rats : a comparison of the effects of different compounds
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Studies of anaesthesia and analgesia in rats and rabbit were undertaken with the aim to improve anaesthesia techniques, for better animal welfare and research quality. Induction of anaesthesia with the volatile halogenated agents isoflurane, sevoflurane and desflurane was compared in the New Zealand White rabbit. All agents caused struggling, breath holding and reflex bradycardia, desflurane having the least detrimental effects. Hypoxia was prevented by pre-oxygenation, and no cardiac arrhythmias were seen. Still, induction of anaesthesia in rabbits cannot be recommended with any of these agents. Injection anaesthesia with ketamine (cyclohexamine)/medetomidine (alpha-2-adrenergic agonist) and the effect of adding the opioid butorphanol, were evaluated in the New Zealand White rabbit. Additionally, effects after subcutaneous and intramuscular administration of ketamine/medetomidine were compared. In a first study, a dose of 15/0.25 mg/kg of ketamine/medetomidine was found effective in producing surgical anaesthesia for 59 ± 18 min, but failed to produce surgical anaesthesia in some animals in a following study, possibly due to different stress levels at the time of induction. The anaesthetic effects did not differ between the administration routes. Subcutaneous injection was easier to perform and seemed less painful. Pronounced hypoxia developed during anaesthesia (PaO2 4.8 ± 0.6 kPa, mean ± SD), indicating a need for oxygen supplementation. Blind tracheal intubation was easy to perform during anaesthesia. Addition of butorphanol increased duration of anaesthesia. In Wistar rats, anaesthesia with ketamine/medetomidine, repeated six times with weekly intervals, and the effects of pre-medication with the opioid buprenorphine, were evaluated. Buprenorphine caused an increase in duration of anaesthesia as well as greater respiratory depression, and was associated with increased lethality. Repeated anaesthesia without buprenorphine was found safe and led to an increase in sleep times with successive anaesthetics. The combination sufentanil (opioid)/medetomidine was also evaluated in Wistar rats. Anaesthesia was more efficiently produced after subcutaneous than after intraperitoneal administration, and a sc dose of 40/150 (mu)g/kg of sufentanil/medetomidine produced surgical anaesthesia for 101 ± 49 min. Anaesthesia resulted in very low oxygen saturation levels (40 ± 20 %). Despite this, all animals recovered uneventfully. Oxygen supplementation is strongly recommended with this combination. Anaesthesia was reversed within 7 min by administration of 0.2/0.5 mg/kg of butorphanol (mixed (mu)-opioid agonist/antagonist)/atipamezole (alpha-adrenergic antagonist). Postoperative recovery and behavior were compared in Sprague-Dawley rats after abdominal surgery under isoflurane or ketamine/medetomidine anaesthesia, and the effect of perioperative treatment with the NSAID analgesic carprofen studied. Surprisingly, rats recovered body weight faster and showed less pain-related behavior when surgery was performed under isoflurane anaesthesia, and locomotion was also less reduced. The effects on body weight after surgery under ketamine/medetomidine anaesthesia were not just seen in the immediate postoperative period, but also for several days after. Perioperative treatment with carprofen reduced the detrimental effects in both isoflurane and ketamine/medetomidine anaesthetized animals. The results show that the choice of anaesthesia may be just as important as the use of analgesic treatment for improved recovery and reduction of pain after surgery.
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| 9. |
- Hedenqvist, Patricia, et al.
(author)
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Anaesthesia in medetomidine premedicated New Zealand White rabbits: a comparison between intravenous sufentanil-midazolam and isoflurane anaesthesia for orthopaedic surgery
- 2014
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In: Laboratory Animals. - : SAGE Publications. - 0023-6772 .- 1758-1117. ; 48, s. 155-163
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Journal article (peer-reviewed)abstract
- Eighteen female New Zealand White rabbits (3.9 +/- 0.4 kg) were anaesthetized with sufentanil-midazolam by intravenous infusion (SUF-MID, n = 9) or isoflurane (ISO, n = 9) for bilateral creation of an osteochondral defect in the medial femur condyle. Subcutaneous premedication with 0.1 mg/kg medetomidine and anaesthesia induction by intravenous infusion of 1.1 mu g/kg sufentanil and 0.2 mg/kg midazolam were identical in both groups. During surgery (60 min), the effects on respiratory and circulatory variables serum lactate, total protein and blood glucose were examined. Intermittent positive pressure ventilation (IPPV) was initiated if apnoea lasted>30 s or if end-tidal CO2 >= 8 kPa. The righting reflex was lost in 3 min. IPPV was necessary during most of the anaesthesia for most of the rabbits. Maintenance doses during surgery were 2.0 mu g/kg/h sufentanil and 0.4 mg/kg/h midazolam, and 1.4% isoflurane, respectively. Mean arterial blood pressure (MAP) was higher in group SUF-MID than group ISO during surgery (63 +/- 12 vs 50 +/- 8 mmHg). In group ISO the heart rate was higher during surgery than before anaesthesia (197 +/- 26 vs 158 +/- 40 bpm) as was blood glucose (9 +/- 2 vs 12 +/- 3 mmol/L). Serum lactate levels remained unchanged whereas total protein decreased in both groups. Time to recover from anaesthesia did not differ between groups (20 min). Intravenous sufentanil-midazolam infusion provided surgical anaesthesia with a higher MAP than isoflurane anaesthesia. The protocol can be useful in situations in which gas anaesthesia cannot be used or in animals with limited cardiovascular reserves. However, IPPV is necessary.
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| 10. |
- Hedenqvist, Patricia, et al.
(author)
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Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting
- 2016
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In: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 107, s. 123-131
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Journal article (peer-reviewed)abstract
- In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10 x 10 mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n = 9) or buprenorphine plus saline (n = 9) postoperatively. Buprenorphine was administered subcutaneously every 6 h for 3 days in a tapered dose (0.05-0.01 mg/kg) and carprofen (5 mg/kg) or saline administered subcutaneously 1 h before, and daily for 4 days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13 h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 43 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5 mg/kg carprofen once daily for 5 days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.
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