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Abstract

Objective—To compare the effects of pretreatment with dexamethasone, physical stress (exercise), or both on sedation and plasma hormone and glucose concentrations in dogs treated with dexmedetomidine (DEX).

Animals—6 healthy purpose-bred Beagles.

Procedure—Dogs received 4 treatments each in a randomized order prior to IV administration of DEX (5 µg/kg). Pretreatments were as follows: (1) IV administration of saline (0.9% NaCl) solution and no exercise (control group); (2) IV administration of dexamethasone (0.05 mg/kg) and no exercise (DM group); (3) IV administration of saline solution and exercise (EX group; 15 minutes of trotting on a treadmill at a speed of 2 m/s); and 4) IV administration of dexamethasone and exercise (DM+EX group).

Results—Following DEX administration, all dogs had similar times to recumbency and sedation index values, irrespective of pretreatment with dexamethasone or exercise. Plasma catecholamine concentrations decreased after DEX administration. Compared with control group dogs, plasma cortisol concentrations were higher in EX-group dogs prior to DEX administration and lower in DM- and DM+EX-group dogs following DEX administration. Administration of DEX decreased plasma cortisol concentration in EX-group dogs only. Plasma glucose concentration was not influenced by exercise or dexamethasone administration but was lower than baseline concentrations at 30 minutes after DEX administration and returned to baseline values by 90 minutes. Heart and respiratory rates and rectal temperature increased during exercise. After DEX administration, these values decreased below baseline values. The decrease in heart rate was of shorter duration in dogs that underwent pretreatment with dexamethasone, exercise, or both than in control group dogs

Conclusions and Clinical Relevance—Pretreatment with dexamethasone, moderate physical stress (exercise), or both did not influence sedation or cause adverse effects in healthy dogs treated with DEX. (Am J Vet Res 2005;66:260–265)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs.

Animals—6 neutered male Beagles.

Procedures—Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test.

Results—Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean ± SD maximum concentration was 85.9 ± 11.9 mg/L and 58.1 ± 17.6 mg/L, and area under the time-concentration curve was 960 ± 233 mg/L•h and 373 ± 133 mg/L•h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations.

Conclusions and Clinical Relevance—After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate heart rate characteristics in dogs undergoing ovariohysterectomy following premedication with medetomidine or acepromazine.

Design—Clinical trial.

Animals—43 client-owned dogs.

Procedure—24-hour ambulatory electrocardiography was performed beginning approximately 1 hour prior to administration of premedications. Dogs were premedicated with medetomidine and butorphanol (n = 21) or acepromazine and butorphanol (22) and, approximately 85 minutes later, were anesthetized with propofol and isoflurane. Electrocardiographic recordings were examined to determine heart rate, cardiac conduction disturbances (ventricular premature complexes and atrioventricular block), and indices of heart rate variability (HRV).

Results—Minimum heart rate during the 24-hour recording period was significantly lower among dogs given medetomidine than among dogs given acepromazine, but during the postoperative period, heart rate increased in all dogs as they became physically active. Intraoperative time domain HRV indices were lower and the low frequency-to-high frequency ratio was higher among dogs given acepromazine than among dogs given medetomidine; however, significant differences between groups were no longer seen by 6 hours after surgery. There was no significant difference between groups with regard to the number of ventricular premature complexes or to values of scaling exponent α2 (a nonlinear measure of HRV).

Conclusions and Clinical Relevance—Results suggest that there are greater enhancements in vagally related heart rate indices in medetomidine-treated dogs that may persist until 6 hours after surgery. Despite the low heart rates, dogs given medetomidine showed expected responses to surgery and positional stimuli, and the 2 preanesthetic protocols may not result in different prevalences of ventricular premature complexes. (J Am Vet Med Assoc 2005;226:738–745)

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the adverse effects of carprofen in dogs after oral administration for 2 months.

Design—Prospective, randomized, blinded, placebo-controlled clinical trial.

Animals—22 dogs with osteoarthritis in the hip or elbow joint.

Procedure—13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, γ-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects.

Results—Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group.

Conclusions and Clinical Relevance—It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To assess the possible impact of medetomidine on concentrations of alfaxalone in plasma, when coadministered as a constant rate infusion (CRI) to dogs, and to determine the possible impact of medetomidine on the cardiopulmonary effects of alfaxalone during CRI.

ANIMALS 8 healthy adult Beagles.

PROCEDURES 3 treatments were administered in a randomized crossover design as follows: 1 = saline (0.9% NaCl) solution injection, followed in 10 minutes by induction of anesthesia with alfaxalone (loading dose, 2.4 mg/kg; CRI, 3.6 mg/kg/h, for 60 minutes); 2 = medetomidine premedication (loading dose, 4.0 μg/kg; CRI, 4.0 μg/kg/h), followed by alfaxalone (as in treatment 1); and, 3 = medetomidine (as in treatment 2) and MK-467 (loading dose, 150 μg/kg; CRI, 120 μg/kg/h), followed by alfaxalone (as in treatment 1). The peripherally acting α2-adrenoceptor antagonist MK-467 was used to distinguish between the peripheral and central effects of medetomidine. Drugs were administered IV via cephalic catheters, and there was a minimum of 14 days between treatments. Cardiopulmonary parameters were measured for 70 minutes, and jugular venous blood samples were collected until 130 minutes after premedication. Drug concentrations in plasma were analyzed with liquid chromatography–tandem mass spectrometry.

RESULTS The characteristic cardiovascular effects of medetomidine, such as bradycardia, hypertension, and reduction in cardiac index, were obtunded by MK-467. The concentrations of alfaxalone in plasma were significantly increased in the presence of medetomidine, indicative of impaired drug distribution and clearance. This was counteracted by MK-467.

CONCLUSIONS AND CLINICAL RELEVANCE The alteration in alfaxalone clearance when coadministered with medetomidine may be attributed to the systemic vasoconstrictive and bradycardic effects of the α2-adrenoceptor agonist. This could be clinically important because the use of α2-adrenoceptor agonists may increase the risk of adverse effects if standard doses of alfaxalone are used.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate protein expression in bronchoalveolar lavage fluid (BALF) obtained from West Highland White Terriers with idiopathic pulmonary fibrosis (IPF), dogs with chronic bronchitis, and healthy control dogs to identify potential biomarkers for IPF.

Samples—BALF samples obtained from 6 West Highland White Terriers with histologically confirmed IPF, 5 dogs with chronic bronchitis, and 4 healthy Beagles.

Procedures—Equal amounts of proteins in concentrated BALF samples were separated via 2-D differential gel electrophoresis. Proteins that were differentially expressed relative to results for healthy control dogs were identified with mass spectrometry and further verified via western blotting.

Results—Expression of 6 proteins was upregulated and that of 1 protein was downregulated in dogs with IPF or chronic bronchitis, compared with results for healthy dogs. Expression of proteins β-actin, complement C3, α-1-antitrypsin, apolipoprotein A-1, haptoglobin, and transketolase was upregulated, whereas expression of lysozyme C was downregulated.

Conclusions and Clinical Relevance—Proteomics can be used to search for biomarkers and to reveal disease-specific mechanisms. The quantitative comparison of proteomes for BALF obtained from dogs with IPF and chronic bronchitis and healthy dogs revealed similar changes for the dogs with IPF and chronic bronchitis, which suggested a common response to disease processes in otherwise different lung diseases. Specific biomarkers for IPF were not identified.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate perfusion of abdominal organs in healthy cats by use of contrastenhanced ultrasonography.

Animals—10 young healthy anesthetized cats.

Procedures—Contrast-enhanced ultrasonography of the liver, left kidney, pancreas, small intestine, and mesenteric lymph nodes was performed on anesthetized cats.

Results—Typical perfusion patterns were found for each of the studied organs. Differences in perfusion among organs were associated with specific physiologic features. The liver was enhanced gradually and had a more heterogeneous perfusion pattern because of its dual blood supply and close proximity to the diaphragm, compared with other organs. An obvious and significant difference in perfusion was detected between the renal cortex and medulla. No significant differences in perfusion were detected among the pancreas, small intestine, and mesenteric lymph nodes.

Conclusions and Clinical Relevance—Results indicated that contrast-enhanced ultrasonography can be used in cats to estimate organ perfusion as in other species. Observed differences in perfusion variables can be mostly explained by physiologic differences in vascularity. (Am J Vet Res 2010;71:1305–1311)

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone.

ANIMALS

8 healthy Beagles.

PROCEDURES

Dogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 μg/kg], medetomidine [20 μg/kg] and vatinoxan [400 μg/kg], and medetomidine [40 μg/kg] and vatinoxan [800 μg/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments.

RESULTS

Plasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were noninferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration.

Animals—8 crossbred pigs.

Procedures—Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (Cmax).

Results—Equivalence was not detected in the AUCs among the various routes of administration nor in Cmax between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean ± SD Cmax was 5.09 ± 1.41 μg/mL and 7.62 ± 1.22 μg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 ± 0.90 hours after oral administration of 3 mg/kg to 2.66 ± 0.50 hours after IV administration. Time to peak Cmax after administration of all treatments was approximately 1 hour. Increases in AUC and Cmax were proportional when the orally administered dose was increased from 3 to 6 mg/kg.

Conclusions and Clinical Relevance—Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To compare cardiovascular effects of premedication with medetomidine alone and with each of 3 doses of MK-467 or after glycopyrrolate in dogs subsequently anesthetized with isoflurane.

ANIMALS 8 healthy purpose-bred 5-year-old Beagles.

PROCEDURES In a randomized crossover study, each dog received 5 premedication protocols (medetomidine [10 μg/kg, IV] alone [MED] and in combination with MK-467 at doses of 50 [MMK50], 100 [MMK100], and 150 [MMK150] μg/kg and 15 minutes after glycopyrrolate [10 μg/kg, SC; MGP]), with at least 14 days between treatments. Twenty minutes after medetomidine administration, anesthesia was induced with ketamine (0.5 mg/kg, IV) and midazolam (0.1 mg/kg, IV) increments given to effect and maintained with isoflurane (1.2%) for 50 minutes. Cardiovascular variables were recorded, and blood samples for determination of plasma dexmedetomidine, levomedetomidine, and MK-467 concentrations were collected at predetermined times. Variables were compared among the 5 treatments.

RESULTS The mean arterial pressure and systemic vascular resistance index increased following the MED treatment, and those increases were augmented and obtunded following the MGP and MMK150 treatments, respectively. Mean cardiac index for the MMK100 and MMK150 treatments was significantly greater than that for the MGP treatment. The area under the time-concentration curve to the last sampling point for dexmedetomidine for the MMK150 treatment was significantly lower than that for the MED treatment.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated concurrent administration of MK-467 with medetomidine alleviated medetomidine-induced hemodynamic changes in a dose-dependent manner prior to isoflurane anesthesia. Following MK-467 administration to healthy dogs, mean arterial pressure was sustained at acceptable levels during isoflurane anesthesia.

Full access
in American Journal of Veterinary Research