Search Results

You are looking at 1 - 7 of 7 items for

  • Author or Editor: Cynthia Kollias-Baker x
  • Refine by Access: All Content x
Clear All Modify Search

Abstract

Objective—To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles.

Animals—6 healthy adult horses.

Procedure—Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, IV) administration followed immediately by IV administration of saline (0.9% NaCl) solution, low-dose morphine (0.1 mg/kg), or high-dose morphine (0.2 mg/kg). Selected parameters of cardiopulmonary function were also determined over time to verify consistency of conditions.

Results—Mean (± SEM) MAC of halothane was 1.05 ± 0.02% and was decreased by 20.1 ± 6.6% at 49 ± 2 minutes following xylazine administration. The amount of MAC reduction in response to xylazine was time dependent. Addition of morphine to xylazine administration did not contribute further to the xylazine-induced decrease in MAC (reductions of 21.9 ± 1.2 and 20.7 ± 1.5% at 43 ± 4 and 40 ± 4 minutes following xylazine-morphine treatments for low-and high-dose morphine, respectively). Overall, cardiovascular and respiratory values varied little among treatments. Kinetic parameters describing plasma concentration-time curves for xylazine were not altered by the concurrent administration of morphine.

Conclusions and Clinical Relevance—Administration of xylazine decreases the anesthetic requirement for halothane in horses. Concurrent morphine administration to anesthetized horses does not alter the anesthetic sparing effect of xylazine or its plasma concentration-time profile. (Am J Vet Res 2004; 65:519–526)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses.

Sample Population—Jejunal muscle strips from 8 horses.

Procedure—Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined.

Results—Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151 ± 214 g/cm2 and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028 ± 0.002 µM. Prior incubation with the 5-HT2 antagonist ketanserin decreased the Emax (626 ± 147 g/cm2) and potency (EC50, 0.307 ± 0.105 µM) of 5-HT. Prior incubation with the 5-HT3 antagonist tropisetron decreased the efficacy (Emax, 894 ± 184 g/cm2) to 5-HT. Cisapride also caused a concentrationdependent increase in contractile amplitude, with an Emax of 331 ± 82 g/cm2 and an EC50 of 0.302 ± 0.122 µM. Prior incubation with ketanserin decreased the Emax (55 ± 17 g/cm2) and potency (EC50, 0.520 ± 0.274 µM) of cisapride.

Conclusion and Clinical Relevance—Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2 and 5-HT3 receptors, whereas the effects of cisapride are mediated primarily by 5-HT2 receptors. This may impact treatment of horses with postoperative ileus. (Am J Vet Res 2000;61:1561–1565)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate accumulation of extracellular adenosine (ADO) by equine articular chondrocytes and to compare effects of adenosine kinase inhibition and adenosine deaminase inhibition on the amount of nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated chondrocytes.

Sample Population—Articular cartilage from metacarpophalangeal and metatarsophalangeal joints of 14 horses.

Procedure—Chondrocytes were cultured as monolayers, and cells were incubated with LPS, the adenosine kinase inhibitor 5'-iodotubercidin (ITU), or the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3- nonyl)adenine hydrochloride (EHNA). Concentrations of ADO in cell supernatants were measured by use of reverse-phase high-performance liquid chromatography. Effect of inhibition of enzymatic metabolism of ADO on induced NO production was evaluated by exposing cells to a combination of LPS and ITU or LPS and EHNA.

Results—Articular chondrocytes accumulated extracellular ADO when exposed to LPS or ITU. Chondrocytes exposed to ITU accumulated ADO in a time-dependent manner. Unstimulated chondrocytes did not accumulate ADO. Similarly, EHNA alone did not produce detectable ADO concentrations; however, addition of EHNA and ITU resulted in a synergistic effect on accumulation of ADO. Lipopolysaccharideinduced NO production was more effectively suppressed by exposure to ITU than to EHNA

Conclusions and Clinical Relevance—Equine articular chondrocytes release ADO in response to the proinflammatory stimulus of bacterial LPS. Inhibition of the metabolism of ADO increases accumulation of extracellular ADO. Autocrine release of ADO from chondrocytes may play a role in the cellular response to tissue damage in arthritic conditions, and pharmacologic modulation of these pathways in joints of arthritic horses could be a potential method of therapy. (Am J Vet Res 2002;63:1512–1519)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of IV and oral administration of AZA in horses.

Animals—6 horses.

Procedure—In study phase 1, a single dose of AZA was administered IV (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for 30 days. Throughout study phase 2, blood samples were collected for CBC determination and serum biochemical analysis.

Results—Plasma concentrations of AZA and its metabolite, 6-MP, decreased rapidly from plasma following IV administration of AZA, consistent with the short mean elimination half-life of 1.8 minutes. Oral bioavailability of AZA was low, ranging from 1% to 7%. No horses had abnormalities on CBC determination or serum biochemical analysis, other than 1 horse that was lymphopenic on day 5 and 26 of daily treatment. This horse developed facial alopecia from which 1 colony of a Trichophyton sp was cultured; alopecia resolved within 1 month after the study ended.

Conclusions and Clinical Relevance—Overall, no adverse effects were observed with long-term oral administration of AZA to horses, although 1 horse did have possible evidence of immunosuppression with chronic treatment. Further investigation of the clinical efficacy of AZA in the treatment of autoimmune diseases in horses is warranted. (Am J Vet Res 2005;66:1578–1583)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys.

Animals—6 adult male rhesus monkeys.

Procedure—Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory.

Results—Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, PaCO2, and PaO2 ranged from 7.46 ± 0.04 to 7.51 ± 0.05 units, 29.2 ± 3 to 34.6 ± 4.4 mm Hg, and 412.6 ± 105.3 to 482.9 ± 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 ± 2.48 ml/kg/min, 9.04 ± 1.91 L/kg, 7.0 ± 1.2 L/kg, 218.5 ± 35.5 min, 0.247 ± 0.019 mg/ml/min, 0.004 ± 0.001/min, and 192.0 ± 33.5 min, respectively.

Conclusions and Clinical Relevance—Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans. (Am J Vet Res 2000;61:931–934)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs.

Animals—8 mixed-breed adult dogs.

Procedure—Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 µg/kg of body weight, IV) that was followed by a constant infusion (0.3 µg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again.

Results—Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80 ± 0.21 to 0.85 ± 0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48 ± 0.29%) was significantly less than isoflurane-fentanylsaline MAC (0.79 ± 0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyldiazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups.

Conclusion and Clinical Relevance—Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs. (Am J Vet Res 2001;62:555–560)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the use of xylazine and ketamine for total IV anesthesia in horses.

Animals—8 horses.

Procedure—Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, IV), guaifenesin (75 mg/kg, IV), and ketamine (2 mg/kg, IV). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (µg/kg/min) and X and K represent xylazine and ketamine, respectively: X35+K90 with 100% inspired oxygen (O2), X35+K120-O2, X35+K150-O2, X70+K90-O2, K150-O2, and X35+K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated.

Results—Heart rate and cardiac index were higher and total peripheral resistance lower in K150-O2 and X35+K120-air groups. The mean arterial pressure was highest in the X35+K120-air group and lowest in the K150-O2 group (125 ± 6 vs 85 ± 8 at 20 minutes, respectively). Mean PaO2 was lowest in the X35+K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-O2 (23 ± 6 minutes and 33 ± 8 minutes, respectively) and longest for those receiving X70+K90-O2 (58 ± 28 minutes and 69 ± 27 minutes, respectively).

Conclusions and Clinical Relevance—Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses. (Am J Vet Res 2005;66:1002–1007)

Full access
in American Journal of Veterinary Research