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  • Author or Editor: Yoshiaki Hikasa x
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Abstract

Objective—To investigate dose-related diuretic effects of medetomidine hydrochloride and xylazine hydrochloride in healthy cats.

Animals—5 sexually intact cats (4 males and 1 female).

Procedures—The 5 cats received each of 11 treatments. Cats were treated by IM administration of saline (0.9% NaCl) solution (control treatment), medetomidine hydrochloride (20, 40, 80, 160, and 320 μg/kg), and xylazine hydrochloride (0.5, 1, 2, 4, and 8 mg/kg). Urine and blood samples were collected 9 times during a 24-hour period. Variables measured were urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine and electrolyte concentrations as well as osmolality in both urine and plasma.

Results—Both medetomidine and xylazine increased urine production for up to 5 hours after injection. Xylazine had a dose-dependent diuretic effect, but medetomidine did not. Urine specific gravity and osmolality decreased in a dose-dependent manner for both drugs. Free-water clearance increased for up to 5 hours after injection, whereas glomerular filtration rate, osmolar clearance, plasma osmolality, and electrolyte concentrations did not change significantly. Area under the curve for AVP concentrations decreased in a dose-dependent manner for medetomidine but not for xylazine; however, this was not related to diuresis.

Conclusions and Clinical Relevance—Both medetomidine and xylazine induced profound diuresis in cats by decreasing reabsorption of water in the kidneys. The diuretic effect of medetomidine, including the change in AVP concentration, differed from that of xylazine. Care must be used when administering these drugs to cats with urinary tract obstruction, hypovolemia, or dehydration.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets.

SAMPLE

Blood samples from 12 healthy adult cats.

PROCEDURES

In 7 experiments, the effects of 23 imidazoline and nonimidazoline α-adrenoceptor agonists or antagonists on aggregation and antiaggregation of feline platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation.

RESULTS

Platelet aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline induced a dose-dependent potentiation of ADP- or collagen-induced aggregation. Oxymetazoline and xylometazoline also induced a small potentiation of ADP-stimulated aggregation, but other α-adrenoceptor agonists did not induce potentiation. The α2-adrenoceptor antagonists and certain imidazoline α-adrenergic agents including phentolamine, yohimbine, atipamezole, clonidine, medetomidine, and dexmedetomidine inhibited adrenaline-potentiated aggregation induced by ADP or collagen in a dose-dependent manner. The imidazoline compound antazoline inhibited adrenaline-potentiated aggregation in a dose-dependent manner. Conversely, α1-adrenoceptor antagonists and nonimidazoline α-adrenergic agents including xylazine and prazosin were ineffective or less effective for inhibiting adrenaline-potentiated aggregation. Moxonidine also was ineffective for inhibiting adrenaline-potentiated aggregation induced by collagen. Medetomidine and xylazine did not reverse the inhibitory effect of atipamezole and yohimbine on adrenaline-potentiated aggregation.

CONCLUSIONS AND CLINICAL RELEVANCE

Adrenaline-potentiated aggregation of feline platelets may be mediated by α2-adrenoceptors, whereas imidazoline agents may inhibit in vitro platelet aggregation via imidazoline receptors. Imidazoline α-adrenergic agents may have clinical use for conditions in which there is platelet reactivity to adrenaline. Xylazine, medetomidine, and dexmedetomidine may be used clinically in cats with minimal concerns for adverse effects on platelet function.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration.

ANIMALS

72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020.

PROCEDURES

For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery.

RESULTS

Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone.

CLINICAL RELEVANCE

Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.

Open access
in American Journal of Veterinary Research

Abstract

Objective—To examine stress-related neurohormonal and metabolic effects of butorphanol, fentanyl, and ketamine administration alone and in combination with medetomidine in dogs.

Animals—10 Beagles.

Procedure—5 dogs received either butorphanol (0.1 mg/kg), fentanyl (0.01 mg/kg), or ketamine (10 mg/kg) IM in a crossover design. Another 5 dogs received either medetomidine (0.02 mg/kg) and butorphanol (0.1 mg/kg), medetomidine and fentanyl (0.01 mg/kg), medetomidine and ketamine (10 mg/kg), or medetomidine and saline (0.9% NaCl) solution (0.1 mL/kg) in a similar design. Blood samples were obtained for 6 hours following the treatments. Norepinephrine, epinephrine, cortisol, glucose, insulin, and nonesterified fatty acid concentrations were determined in plasma.

Results—Administration of butorphanol, fentanyl, and ketamine caused neurohormonal and metabolic changes similar to stress, including increased plasma epinephrine, cortisol, and glucose concentrations. The hyperglycemic effect of butorphanol was not significant. Ketamine caused increased norepinephrine concentration. Epinephrine concentration was correlated with glucose concentration in the butorphanol and fentanyl groups but not in the ketamine groups, suggesting an important difference between the mechanisms of the hyperglycemic effects of these drugs. Medetomidine prevented most of these effects except for hyperglycemia. Plasma glucose concentrations were lower in the combined sedation groups than in the medetomidine-saline solution group.

Conclusions and Clinical Relevance—Opioids or ketamine used alone may cause changes in stressrelated biochemical variables in plasma. Medetomidine prevented or blunted these changes. Combined sedation provided better hormonal and metabolic stability than either component alone. We recommend using medetomidine-butorphanol or medetomidine-ketamine combinations for sedation or anesthesia of systemically healthy dogs. (Am J Vet Res 2005;66:406–412)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate effects of various imidazoline and nonimidazoline α-adrenergic agents on aggregation and antiaggregation of bovine and equine platelets.

Sample—Blood samples obtained from 8 healthy adult cattle and 16 healthy adult Thoroughbreds.

Procedures—Aggregation and antiaggregation effects of various imidazoline and nonimidazoline α-adrenergic agents on bovine and equine platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation.

Results—Adrenaline, noradrenaline, or α-adrenoceptor agents alone did not induce changes in aggregation of bovine or equine platelets or potentiate ADP- or collagen-induced platelet aggregation. Adrenaline and the α2-adrenoceptor agonist clonidine had an inhibitory effect on ADP- and collagen-induced aggregation of bovine platelets. The α2-adrenoceptor antagonists phentolamine and yohimbine also inhibited collagen-induced aggregation of bovine platelets. Noradrenaline, other α-adrenoceptor agonists (xylazine, oxymetazoline, and medetomidine), and α-adrenoceptor antagonists (atipamezole, idazoxan, tolazoline, and prazosin) were less effective or completely ineffective in inhibiting ADP- and collagen-induced aggregation of bovine platelets. The imidazoline α2-adrenoceptor agonist oxymetazoline submaximally inhibited collagen-induced aggregation of equine platelets, and the α2-adrenoceptor antagonist idazoxan, along with phentolamine and yohimbine, also inhibited collagen-induced aggregation of equine platelets. The imidazoline compound antazoline inhibited both ADP- and collagen-induced aggregation of equine platelets.

Conclusions and Clinical Relevance—Several drugs had effects on aggregation of platelets of cattle and horses, and effective doses of ADP and collagen also differed between species. The α2-adrenoceptor agonists (xylazine and medetomidine) and antagonists (tolazoline and atipamezole) may be used by bovine and equine practitioners without concern for adverse effects on platelet function and hemostasis.

Full access
in American Journal of Veterinary Research