Effect of fentanyl constant-rate infusions with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement in dogs.

Propofol is a potential injectable anesthetic agent used in total intravenous anesthesia. However, the sparing effect of fentanyl and medetomidine on the required propofol dose in dogs remains unclear. We aimed to investigate the effect of fentanyl constant-rate infusion (CRI) with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement (MIRNM) in dogs. Six healthy purpose-bred dogs were anesthetized on three occasions with propofol alone (loading dose [LD], 8 mg/kg to effect; initial infusion rate [IR], 0.70 mg/kg/min); propofol (LD, 6 mg/kg to effect; IR, 0.35 mg/kg/min) and fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min); or propofol (LD, 4 mg/kg to effect; IR, 0.25 mg/kg/min), fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min), and medetomidine (LD, 2 µg/kg; IR, 0.5 µg/kg/hr) under controlled ventilation. The MIRNM was determined by observing the response to a noxious electrical stimulus. Heart rate, blood pressure, and blood gas analyses were performed at 1, 2, 3, and 4 hr after initiating CRI. The MIRNM (mean [range]) was significantly lower in the propofol-fentanyl-medetomidine group (0.16 [0.10-0.27] mg/kg/min) than that in the propofol-alone group (0.63 [0.47-0.82] mg/kg/min) (P=0.0004). Fentanyl combined with medetomidine did not significantly decrease the mean arterial pressure in dogs receiving propofol CRI 1-3 hr after initiating CRI compared with propofol CRI alone (P>0.9999, P=0.1536, and P=0.0596, respectively), despite inducing a significantly lower heart rate.

Magnetic resonance imaging findings of the primitive neuroectodermal tumour in lumbosacral spinal cord in a cat.

A 5-year-old, castrated, male domestic short-haired cat presented with neurological deficits in the pelvic limbs, back pain and dysuria. Magnetic resonance imaging showed a mass lesion caudal to the L4 vertebrae. In addition, suspected haemorrhage was observed at the cranial aspect of the mass. There was no evidence to support the presence of extravertebral intrusion or vertebral body, osteolysis. Dorsal laminectomy and durotomy were performed to debulk the intraspinal mass. Histopathological and immunohistochemical assessment revealed a primitive neuroectodermal tumour (PNET). To our knowledge, this is the first report to describe the clinical and pathological features and imaging diagnosis of intraspinal PNET without extraspinal invasion in a cat.

Variation in Diffusion Tensor Imaging Parameters in the Cervical and Thoracic Spinal Cord (C1-C5 and C6-T2) Segments of Normal Beagle Dogs.

This study aimed to determine the characteristics and reference values of each vertebra in the cervicothoracic region by performing diffusion tensor imaging (DTI) scans and analyzing DTI parameters in normal Beagle dogs. In five adult Beagles under anesthetic maintenance, DTI was performed using a 1.5-T magnetic resonance imaging (MRI) scanner. Axial DTI was performed using three overlapping slabs to cover the cervical and thoracic spinal cords. After post-processing, DTI parameters were calculated along the entire spinal cord. Among DTI parameters, fractional anisotropy, relative anisotropy, and axonal diffusivity significantly decreased in the caudal direction. However, the apparent diffusion coefficient, radial diffusivity, and mean diffusivity values were not significantly correlated with vertebral levels. We provide evidence for the existence of segment-dependent DTI parameters in the canine cervical spinal cord. Therefore, comparisons of DTI parameters between lesions at different vertebral levels should be avoided unless normative data are available. Furthermore, the DTI data obtained in this study may contribute to the development of a clinical reference for spinal cord evaluation in dogs using DTI parameters.

Distal renal tubular acidosis and lethargy associated with zonisamide treatment in a dog with idiopathic epilepsy.

A 3-year-old neutered male golden retriever administered zonisamide for the treatment of seizures showed lethargy and had normal anion gap metabolic acidosis with hypokalaemia, hyperchloremia, and alkaline urine. The serum zonisamide concentration was close to the upper limit, which raised a suspicion of adverse effects of zonisamide. This is the first report showing that the fractional excretion of bicarbonate after compensation for the plasma bicarbonate concentration by a sodium bicarbonate infusion was approximately 5%, indicating distal renal tubular acidosis (RTA). The serum zonisamide concentration decreased, and adverse effects were abated by reducing the zonisamide dosage. Diagnostic therapy with bicarbonate served as a means of compensating for bicarbonate deficiency and contributed to the clinical diagnosis of the condition in zonisamide-associated RTA in dogs.

Effects of Multimodal Analgesic Protocol, with Buprenorphine and Meloxicam, on Mice Well-Being: A Dose Finding Study.

The anesthetic or analgesic agent of choice, route and frequency of anesthetic or analgesic administration, and stressors induce distress during the perioperative period. We evaluated a multimodal analgesic protocol using buprenorphine and meloxicam on the well-being of mice. Twenty-four Slc:ICR male mice were divided into control, anesthesia + analgesia, and surgery + anesthesia + analgesia groups. Tap water (orally: PO) and water for injection (subcutaneous: SC) were administered to the control group. Buprenorphine was administered twice (SC, 0.1 mg/kg/8 h) and meloxicam was administered thrice (PO, 5 mg/kg/24 h) to the anesthesia + analgesia and surgery + anesthesia + analgesia groups. The mice were subjected to laparotomy and assessed for several parameters. Even in absence of surgical pain, the anesthesia + analgesia group presented the same negative effects as the surgery + anesthesia + analgesia group. This multimodal analgesic protocol for mice was expected to have an analgesic effect on pain associated with laparotomy but was not sufficient to prevent food intake and weight decrease. This does not negate the need to administer analgesics, but suggests the need to focus on and care not only about the approach to relieve pain associated with surgery, but also other types of distresses to minimize negative side effects that may interfere with postoperative recovery in mice.

Effect of a Corset on the Gait of Healthy Beagle Dogs.

The prognosis for intervertebral disc disease (IVDD), a common neurologic disease in dogs, varies, with some cases requiring long-term rehabilitation. Corsets are used as part of the physical rehabilitation of dogs, and one of these, the Anifull Dog's Corset Pro, is manufactured and sold by Daiya Industry Co., Ltd. This corset is used to relieve pain caused by spinal cord and vertebral diseases, and to prevent neurological conditions from worsening, by limiting spinal movement. However, the effect of the Anifull Dog's Corset Pro on gait has not yet been clarified. Therefore, we aimed to evaluate the effects of this corset on the gait of dogs using kinematic and kinetic analyses. Five healthy beagle dogs wearing corsets were trotted, kinematic and kinetic parameters were measured using motion capture and force plates, and the results were compared to those obtained when the dogs were not wearing a corset. The range of motion of the angle formed by the 13th thoracic vertebra and the 7th lumbar vertebra at the apex of the 7th cervical vertebra was significantly reduced in the corset-wearing dogs. Thus, the Anifull Dog's Corset Pro may improve trunk stability without affecting gait.

Effect of Different Doses of Atipamezole on Reversal of Medetomidine-Induced Tear-Flow Decrease in Rats.

It has been reported that α2-adrenoceptor agonists such as medetomidine decrease tear flow in many species, including rats. Few studies have investigated the involvement of α2-adrenoceptor in decreased tear flow; the issue has not been illustrated sufficiently. Therefore, we aimed to investigate the effect of different doses of atipamezole on the reversal of medetomidine-induced tear-flow decrease to reveal the specific involvement of α2-adrenoceptor. Treatment with 400, 800, or 1600 µg/kg atipamezole (or saline as the control) was intramuscularly administered to rats 15 min following intramuscular administration of 200 µg/kg medetomidine. After medetomidine administration, tear flow was measured using a phenol red thread test (PRTT). PRTT values decreased significantly after 200 µg/kg medetomidine administration. The PRTT values after 800 (optimal dose to reverse) and 1600 µg/kg atipamezole administration reached baseline, but never exceeded it significantly. Treatment with 400 µg/kg atipamezole also reversed the decrease in PRTT value but the PRTT remained lower than baseline. The optimal dose and the higher dose of atipamezole fully reversed the medetomidine-induced decrease in tear flow to the baseline level in rats, while the lower dose of atipamezole partially recovered tear flow.

Antiemetic effect of oral maropitant treatment before the administration of brimonidine ophthalmic solution in healthy cats.

OBJECTIVES: The aim of this study was to investigate the antiemetic, behavioural and physiological effects of oral maropitant treatment before the administration of brimonidine ophthalmic solution in healthy cats. METHODS: Five cats received oral maropitant 8 mg or no treatment (control) 18 h before the administration of one drop of brimonidine solution in both eyes. Each cat was administered each of the two treatments, with a washout period of 1 week. The incidence of emesis, retching, sialorrhoea and lip-licking after brimonidine administration was recorded, while behavioural and physiological parameters, including heart rate, mean blood pressure, respiratory frequency and rectal temperature, were recorded before and 0, 30, 60, 90, 120, 180 and 240 mins after brimonidine administration. RESULTS: Emesis and retching were not observed when maropitant was administered. However, 4/5 cats exhibited vomiting and retching in the absence of maropitant pretreatment. The incidence of emesis and retching after brimonidine administration was significantly lower in the treatment group than in the control group. Sialorrhoea occurred in one cat in the control group, while all cats showed lip-licking after brimonidine administration. There were no significant differences in the incidence of sialorrhoea and lip-licking between the two groups. Although behaviour scores were comparable between the two groups, those obtained during heart rate, mean blood pressure and respiratory frequency measurements were significantly lower than the baseline scores; this indicated a sedative effect after brimonidine administration. The heart rate and mean blood pressure significantly decreased after brimonidine administration in both groups, while there were no intergroup differences in the heart rate, mean blood pressure, respiratory frequency and rectal temperature. CONCLUSIONS AND RELEVANCE: Oral maropitant treatment before the administration of brimonidine ophthalmic solution in cats can alleviate emesis and retching without affecting the sedative effects of brimonidine and important physiological parameters.

Effect of intramuscular administration of medetomidine and xylazine on tear flow measured by the Schirmer tear test I in healthy cats.

OBJECTIVES: This study aimed to investigate the effects of intramuscular medetomidine and xylazine on tear flow in healthy cats. METHODS: Five cats each received medetomidine 10, 20, 40 and 80 µg/kg IM; xylazine 1.0, 2.0, 4.0 and 8.0 mg/kg IM; and physiological saline (2.0 ml IM) in a randomised order separated by intervals of at least 1 week. The Schirmer tear test (STT) I was performed in both eyes before and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h after each dose. RESULTS: The STT I value decreased significantly at 0.5 and 1.0 h and at 0.75 and 1.0 h in both eyes after administration of medetomidine at 10 or 40 µg/kg. After administration of medetomidine 80 µg/kg, there was a significant decrease in the STT I reading at 0.75, 2 and 3 h in the left eye and 0.75, 1, 2 and 3 h in the right eye. The STT I value decreased significantly at: 0.5, 0.75, 1 and 2 h in the left eye and 0.75 h in the right eye after administration of xylazine 1.0 mg/kg; 0.5, 0.75, 1 and 2 h in the left eye and 0.5, 0.75, 1 and 3 h in the right eye after administration of xylazine 2.0 mg/kg; 0.5, 0.75, 1 and 2 h in both eyes after administration of xylazine 4.0 mg/kg; and 0.5, 0.75, 1, 2 and 3 h in the left eye and 0.75, 1, 2, 3 and 4 h in the right eye after administration of xylazine 8.0 mg/kg. CONCLUSIONS AND RELEVANCE: Both medetomidine and xylazine significantly decreased feline tear flow measured by STT I. Therefore, the ocular surface should be monitored carefully and protected appropriately in cats treated with these sedatives.

Sedative and physiological effects of brimonidine tartrate ophthalmic solution in healthy cats.

OBJECTIVE: To determine the effects of brimonidine tartrate ophthalmic solution on sedation, heart rate (HR), respiratory frequency (fR), rectal temperature (RT) and noninvasive mean arterial pressure (MAP) in healthy cats. STUDY DESIGN: Randomized, blinded crossover study, with 1 week washout between treatments. ANIMALS: Six healthy purpose-bred cats. METHODS: Brimonidine tartrate ophthalmic solution 0.1% (one or two drops; 58.6 ± 3.3 µg per drop) or a control solution (artificial tear solution) was administered to six healthy cats. Behavioural observations and measurements of HR, fR, RT and MAP were recorded before and at 30, 60, 90, 120, 180, 240, 300 and 360 minutes after topical administration. Behavioural scores were analysed using Friedman's test for repeated measures to evaluate the time effect in each treatment and treatment effect at each time point. Physiological variables (HR, fR, RT and MAP) were analysed using two-way analysis of variance for repeated measures to evaluate the time and treatment effects. The level of significance was set at p < 0.05. RESULTS: Dose-dependent behavioural and physiological responses were noted. A dose of two drops of brimonidine resulted in sedation in the cats and decreased HR and MAP. Significant sedative effects occurred between 30 and 120 minutes and for physiological responses up to 360 minutes. The most frequent adverse reaction was vomiting, occurring within 40 minutes in all six cats administered two drops and five of the six cats administered one drop of brimonidine. CONCLUSIONS AND CLINICAL RELEVANCE: The results demonstrated that ocular administration of brimonidine 0.1% ophthalmic solution induced sedation in cats and some cardiovascular effects usually associated with α2-adrenoceptor agonists. Further studies should be performed to determine clinical applications for this agent in cats.

Escherichia coli-derived recombinant human bone morphogenetic protein-2 combined with bone marrow-derived mesenchymal stromal cells improves bone regeneration in canine segmental ulnar defects.

BACKGROUND: Large bone defects in canines usually require assistance to achieve healing. Implantation of osteoinductive factors can promote bone healing, while transplantation of osteoprogenitor cells can enhance bone regeneration. We hypothesized that implantation of an osteoinductive factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), combined with osteoprogenitor cells, bone marrow-derived mesenchymal stromal cells (BMSCs), would synergistically promote bone healing. In this study, we examined the combined effects of Escherichia coli-derived rhBMP-2 and BMSCs on bone healing after implantation into canine ulnar defects. RESULTS: Critical-sized osteoperiosteal segmental defects (2.5 cm) were created in the ulnae of healthy female beagle dogs, and implanted with combinations of E. coli-derived rhBMP-2 (560 or 140 µg) and autologous BMSCs (10(7), 10(5), or 0 cells). In the present study,18 forelimbs of nine healthy purpose-bred female beagles were used. All six treatment groups contained three forelimbs, and the animals were euthanized after 12 weeks. The control groups (560 and 140 µg/0 cells) were cited from our previous study to reduce the number of experimental animals. Radiographically, the regenerated bone width was significantly increased in the 560 or 140 µg with 10(7) and 10(5) cells groups compared with the 0 cells groups. By quantitative CT, the bone mineral density was higher in the 560 µg with 10(7) and 10(5) cells groups, while non-uniformity of the bone mineral density was improved in the 560 µg with 10(7) and 10(5) cells groups and 140 µg/10(7) cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 µg with 10(7) and 10(5) cells groups. Histologically, the regenerated bone was well-developed and contained osteocyte-like cells marrow cavities, and vessels. However, the osteoclasts and osteoblasts were hardly observed. The osteocyte-like cell numbers were significantly higher in the 560 µg with 10(7) and 10(5) cells and 140 µg with 10(7) and 10(5) cells groups. CONCLUSIONS: Implantation of E. coli-derived rhBMP-2 and BMSCs led to significantly enhanced bone formation, with improved bone mineral density and reduced non-uniformity of the regenerated bone. Combined implantation of rhBMP-2 and BMSCs may be useful for promotion of bone healing in critical-sized defects in canines.

Autotransplanting of bone marrow-derived mononuclear cells for complete cases of canine paraplegia and loss of pain perception, secondary to intervertebral disc herniation.

OBJECTIVES: Severe intervertebral disc herniation causes complete paraplegia and loss of pain sensation in canines. The prognosis is poor, even when decompression surgery is performed immediately after onset. Studies suggest that bone marrow-derived mononuclear cells will regenerate the injured spinal cord and restore neurologic function. This study was conducted to assess the clinical efficacy of bone marrow-derived mononuclear cell autotransplanting in severe cases of canine intervertebral disc herniation. MATERIALS AND METHODS: Eighty-two dogs (miniature dachshunds) with severe thoracolumbar intervertebral disc herniation were used. All had intervertebral disc herniation accompanied by paraplegia and loss of pain perception. In 36 dogs, bone marrow-derived mononuclear cells were autotransplanted to the lesioned spinal cord immediately after decompression surgery. Bone marrow was collected from the proximal humerus and subjected to density gradient centrifugation to isolate the bone marrow-derived mononuclear cells. The remaining 46 dogs (receiving surgical treatment only) were assigned as controls. Therapeutic efficacy was compared based on the rate of ambulatory recovery. RESULTS: Ambulatory recovery was observed in 88.9% and 56.5% of animals in the bone marrow-derived mononuclear cells and control groups, and a significant difference was found. No complications were found in bone marrow-derived mononuclear cells group. CONCLUSIONS: Bone marrow-derived mononuclear cell transplanting revealed a significant increase in the recovery rate and, as has been reported in rats and humans, bone marrow-derived mononuclear cell autotransplanting shows efficacy in canines as well.

Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects.

Because bone morphogenetic protein 2 gene transfected Escherichia coli (E-BMP-2) produce recombinant human BMP-2 (rhBMP-2) more efficiently than mammalian cells (Chinese hamster ovary [CHO]-BMP-2), they may be a more cost-effective source of rhBMP-2 for clinical use. However, use of E-BMP-2 for regenerating long bones in large animals has not been reported. In the current study, we evaluated the healing efficacy of E-BMP-2 in a canine model. We created 2.5-cm critical-size segmental ulnar defects in test animals, then implanted E-BMP-2 and 700 mg of artificial bone (beta-tricalcium phosphate; ß-TCP) into the wounds. We examined the differential effects of 5 E-BMP-2 treatments (0, 35, 140, 560, and 2240 µg) across 5 experimental groups (control, BMP35, BMP140, BMP560, and BMP2240). Radiography and computed tomography were used to observe the regeneration process. The groups in which higher doses of E-BMP-2 were administered (BMP560 and BMP2240) displayed more pronounced bone regeneration; the regenerated tissues connected to the host bone, and the cross-sectional areas of the regenerated bone were larger than those of the originals. The groups in which lower doses of E-BMP-2 were administered (BMP35 and BMP140) experienced relatively less bone regeneration; furthermore, the regenerated tissues failed to connect to the host bone. In these groups, the cross-sectional areas of the regenerated bone were equal to or smaller than those of the originals. No regeneration was observed in the control group. These findings suggest that, like CHO-BMP-2, E-BMP-2 can be used for the regeneration of large defects in long bones and that its clinical use might decrease the cost of bone regeneration treatments.