Kenjiro Miyoshi

Sedative effects of intramuscular alfaxalone administered to cats

The sedative effects of intramuscular (IM) alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (alfaxalone-HPCD) were evaluated in cats. The cats were treated with alfaxalone-HPCD in five occasions with a minimum 14-day interval between treatments: an IM injection of 1.0 mg/kg (IM1), 2.5 mg/kg (IM2.5), 5 mg/kg (IM5) or 10 mg/kg (IM10), or an intravenous injection of 5 mg/kg (IV5). The sedative effects were evaluated subjectively using a composite measurement scoring system (a maximum score of 16). Cardio-respiratory variables were measured non-invasively. The median sedation scores peaked at 10 min (score 9), 15 min (score 14), 10 min (score 16), 10 to 20 min (score 16) and 2 to 5 min (score 16) after the IM1, IM2.5, IM5, IM10 and IV5 treatments, respectively. The IM5 treatment produced longer lasting sedation, compared to the IV5 treatment. Durations of maintenance of lateral recumbency after the IM10 treatment (115 ± 22 min) were longer than those after the IM2.5 (40 ± 15 min), IM5 (76 ± 21 min) and IV5 treatments (50 ± 5 min). Cardio-respiratory variables remained within clinically acceptable ranges, except for each one cat that showed hypotension (<60 mmHg) after the IM10 and IV5 treatments. Tremors, ataxia and opisthotonus-like posture were observed during the early recovery period after the IM2.5, IM5, IM10 and IV5 treatments. In conclusion, IM alfaxalone-HPCD produced dose-dependent and clinically relevant sedative effect at 2.5 to 10 mg/kg in healthy cats. Hypotension may occur at higher IM doses of alfaxalone-HPCD.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone.

Extranodal Lymphoma with Peripheral Nervous System Involvement in a Dog

ABSTRACT An 8-year-old neutered female Cavalier King Charles spaniel was evaluated for progressing right forelimb lameness. Magnetic resonance imaging revealed that the right-side radial nerves and the caudal brachial plexus were swollen. The histological and molecular biological diagnosis by partial biopsy of the C8 spinal nerve was T-cell lymphoma. Coadministration of lomustine and irradiation was started. However, this therapy was ineffective. At necropsy, neoplastic tissues were seen extending into the subarachnoid space of the spinal cord, liver, pancreas and kidneys as gross findings. A large mass was also identified occupying the caudal thorax. Histologic findings included infiltration in these organs and the mass by neoplastic lymphocytes. To date, involvement of peripheral nerves (neurolymphomatosis) is rarely reported in veterinary species.

The pharmacological effects of intramuscular administration of alfaxalone combined with medetomidine and butorphanol in dogs

The pharmacological effects of intramuscular (IM) administration of alfaxalone combined with medetomidine and butorphanol were evaluated in 6 healthy beagle dogs. Each dog received three treatments with a minimum 10-day interval between treatments. The dogs received an IM injection of alfaxalone 2.5 mg/kg (ALFX), medetomidine 2.5 µg/kg and butorphanol 0.25 mg/kg (MB), or their combination (MBA) 1 hr after the recovery from their instrumentation. Endotracheal intubation was attempted, and dogs were allowed to breath room air. Neuro-depressive effects (behavior changes and subjective scores) and cardiorespiratory parameters (rectal temperature, heart rate, respiratory rate, direct blood pressure, central venous pressure and blood gases) were evaluated before and at 2 to 120 min after IM treatment. Each dog became lateral recumbency, except for two dogs administered the MB treatment. The duration was longer in the MBA treatment compared with the ALFX treatment (100 ± 48 min vs 46 ± 13 min). Maintenance of the endotracheal tube lasted for 60 ± 24 min in five dogs administered the MBA treatment and for 20 min in one dog administered the ALFX treatment. Cardiorespiratory variables were maintained within clinically acceptable ranges, although decreases in heart and respiratory rates, and increases in central venous pressure occurred after the MBA and MB treatments. The MBA treatment provided an anesthetic effect that permitted endotracheal intubation without severe cardiorespiratory depression in healthy dogs.

Sparing effect of robenacoxib on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs.

ABSTRACT Robenacoxib is a newer nonsteroidal anti-inflammatory drug approved for dogs and cats. This study was designed to evaluate the effect of robenacoxib on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Sevoflurane MAC-BAR was determined by judging dogs’ response to a noxious electrical stimulus (50 V, 50 Hz and 10 msec) for 10 sec in 6 beagle dogs on two occasions at least a 7-day interval. In each occasion, saline (0.1 ml/kg) or robenacoxib (2 mg/kg) was administered subcutaneously at 1 hr prior to the MAC-BAR determination. Robenacoxib significantly decreased the sevoflurane MAC-BAR (3.44 ± 0.53% for saline vs. 2.84 ± 0.38% for robenacoxib, P=0.039). These results suggest that subcutaneous robenacoxib provides a clinically relevant sparing effect on anesthetic requirement.

Interaction between maropitant and carprofen on sparing of the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs

Maropitant, a neurokinin-1 receptor antagonist, may provide analgesic effects by blocking pharmacological action of substance P. Carprofen is a non-steroidal anti-inflammatory drug commonly used for pain control in dogs. The purpose of this study was to evaluate the effect of a combination of maropitant and carprofen on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Six healthy adult beagle dogs were anesthetized with sevoflurane four times with a minimum of 7-day washout period. On each occasion, maropitant (1 mg/kg) alone, carprofen (4 mg/kg) alone, a combination of maropitant (1 mg/kg) and carprofen (4 mg/kg), or saline (0.1 ml/kg) was subcutaneously administered at 1 hr prior to the first electrical stimulation for the sevoflurane MAC-BAR determination. The sevoflurane MAC-BAR was significantly reduced by maropitant alone (2.88 ± 0.73%, P=0.010), carprofen alone (2.96 ± 0.38%, P=0.016) and the combination (2.81 ± 0.51%, P=0.0003), compared with saline (3.37 ± 0.56%). There was no significant difference in the percentage of MAC-BAR reductions between maropitant alone, carprofen alone and the combination. The administration of maropitant alone and carprofen alone produced clinically significant sparing effects on the sevoflurane MAC-BAR in dogs. However, the combination of maropitant and carprofen did not produce any additive effect on the sevoflurane MAC-BAR reduction. Anesthetic premedication with a combination of maropitant and carprofen may not provide any further sparing effect on anesthetic requirement in dogs.

Stroke volume variation (SVV) and pulse pressure variation (PPV) as indicators of fluid responsiveness in sevoflurane anesthetized mechanically ventilated euvolemic dogs

Changes in stroke volume variation (SVV) and pulse pressure variation (PPV) in response to fluid infusion were experimentally evaluated during vecuronium infusion and sevoflurane anesthesia in 5 adult, mechanically ventilated, euvolemic, beagle dogs. Sequential increases in central venous pressure (CVP; 3–7[baseline], 8–12, 13–17, 18–22 and 23–27 mmHg) were produced by infusing lactated Ringer’s solution and 6% hydroxyethyl starch solution. Heart rate (beats/min), right atrial pressure (RAP, mmHg), pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), transpulmonary thermodilution cardiac output (TPTDCO, l/min), stroke volume (SV, ml/beat), arterial blood pressure (ABP, mmHg), extravascular lung water (EVLW, ml), pulmonary vascular permeability index (PVPI, calculated), SVV (%), PPV (%) and systemic vascular resistance (SVR, dynes/sec/cm5) were determined at each predetermined CVP range. Heart rate (P=0.019), RAP (P<0.001), PAP (P<0.001), PCWP (P<0.001), TPTDCO (P=0.009) and SV (P=0.04) increased and SVR (P<0.001), SVV (P<0.001) and PPV (P<0.001) decreased associated with each stepwise increase in CVP. Arterial blood pressure, EVLW, PVPI and the arterial partial pressures of oxygen and carbon dioxide did not change. The changes in SVV and PPV directly reflected the fluid load and the minimum threshold values for detecting fluid responsiveness were SVV ≥11% and PPV ≥7% in dogs.

Comparison of pharmacokinetics of tramadol between young and middle-aged dogs

This study aimed to compare the pharmacokinetics of tramadol between young and middle-aged dogs. Tramadol (4 mg/kg) was administered intravenously (IV) to young and middle-aged dogs (2 and 8–10 years, respectively). Plasma concentrations of tramadol were measured using high-performance liquid chromatography (HPLC), and its pharmacokinetics best fit a two-compartment model. The volume of distribution (Vd), elimination half-life (t1/2,β) and total body clearance (CLtot) of the young group were 4.77 ± 1.07 l/kg, 1.91 ± 0.26 hr and 29.9 ± 7.3 ml/min/kg, respectively, while those of the middle-aged group were 4.73 ± 1.43 l/kg, 2.39 ± 0.97 hr and 23.7 ± 5.4 ml/min/kg, respectively. Intergroup differences in the t1/2,β and CLtot were significant (P<0.05). In conclusion, tramadol excretion was significantly prolonged in middle-aged dogs.

GM1 gangliosidosis in a Japanese domestic cat: a new variant identified in Hokkaido, Japan

A male Japanese domestic cat with retarded growth in Hokkaido, Japan, showed progressive motor dysfunction, such as ataxia starting at 3 months of age and tremors, visual disorder and seizure after 4 months of age. Finally, the cat died of neurological deterioration at 9 months of age. Approximately half of the peripheral blood lymphocytes had multiple abnormal vacuoles. Magnetic resonance imaging showed bisymmetrical hyperintensity in the white matter of the parietal and occipital lobes in the forebrain on T2-weighted and fluid-attenuated inversion recovery images, and mild encephalatrophy of the olfactory bulbs and temporal lobes. The activity of lysosomal acid β-galactosidase in leukocytes was negligible, resulting in the biochemical diagnosis of GM1 gangliosidosis. Histologically, swollen neurons characterized by accumulation of pale, slightly granular cytoplasmic materials were observed throughout the central nervous system. Dysmyelination or demyelination and gemistocytic astrocytosis were observed in the white matter. Ultrastructually, membranous cytoplasmic bodies were detected in the lysosomes of neurons. However, genetic analysis did not identify the c.1448G>C mutation, which is the single known mutation of feline GM1 gangliosidosis, suggesting that the cat was affected with a new variant of the feline disease.