In vitro effects of a mixture of Escherichia coli heat-stable enterotoxins (STa and STb) on isolated jejunum of 3-week-old male pigs were studied, using everted intestinal sac techniques. Heat-stable enterotoxins increased chloride secretion and chloride absorption in everted intestinal sacs. The increase of secretory flux was greater than that for absorptive flux. Vasoactive intestinal peptide (6 x 10-9M) increased chloride secretion, but had no effect on chloride absorption. Neither vasoactive intestinal peptide nor pilocarpine (10-5M) had additive effect to ST. Secretory effects of ST were not blocked by atropine 2 x 10-5M), clonidine (10-6M), or morphine (4.2 X 10-6M).

OBJECTIVE: To assess the analgesic efficacy of an IV constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination in calves undergoing umbilical herniorrhaphy. ANIMALS: 20 weaned Holstein calves with umbilical hernias. PROCEDURES: Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). The assigned CRI was begun after anesthesia induction. A pain-scoring system and incisional algometry were used to assess pain, and blood samples were obtained to measure serum cortisol concentration at predetermined times for 120 hours after CRI initiation. RESULTS: Mean pain scores did not differ significantly between the MLK and control groups at any time. Mean algometry score for the MLK group was significantly greater (calves were less responsive to pressure) than that for the control group at 4 hours after CRI initiation. Mean cortisol concentration decreased over time for both groups and was significantly greater for the MLK group than the control group at 1, 4, and 18 hours after CRI initiation. CONCLUSIONS AND CLINICAL RELEVANCE: A CRI of MLK provided adequate postoperative analgesia to calves that underwent umbilical herniorrhaphy. However, the technical support required for CRI administration limits its use to hospital settings. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols and withdrawal intervals.

This study evaluated the effects of 3 morphine doses combined with acepromazine, on sedation and physiological parameters in 5 clinically healthy dogs. Four treatments were administered intramuscularly in a randomized, blinded, crossover design: acepromazine, 0.05 mg/kg, alone (ACP) and acepromazine plus morphine at doses of 0.25, 0.5, and 1.0 mg/kg body weight (BW) (AM(0.25), AM(0.5), and AM(1.0), respectively). Sedation scores and cardiorespiratory variables were evaluated for 120 min after drug administration. The sedation scores were significantly higher with the AM(0.25) and AM(1.0) treatments than with the ACP treatment. At 30 min the scores were 36% to 66% higher with AM(1.0) than with AM0.25 and AM0.5, respectively, but these differences were not significant. The physiological variables remained acceptable for dogs. The results of this study do not support the use of AM0.5 over AM(0.25) to improve sedation in dogs, but they do indicate that sedation may be greater with AM(1.0) than with AM(0.25) and AM(0.5). Studies with a greater number of samples are warranted to confirm this statement.

Objective-To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs. Animals-6 healthy adult dogs. Procedures-Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons. Results-Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments. Conclusions and Clinical Relevance-Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs.

This study evaluated the analgesia effects of the epidural administration of 0.1 mg/kg bodyweight (BW) of morphine or 5 micrograms/kg BW of buprenorphine in ponies with radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments: the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl) solution; group M was administered 0.1 mg/kg BW of morphine; and group B was administered 5 micrograms/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right radiocarpal joint. An epidural catheter was later introduced in the lumbosacral space and advanced up to the thoracolumbar level. The treatment started 6 h after synovitis induction. Lameness, maximum angle of carpal flexion, heart rate, systolic arterial pressure, respiratory rate, temperature, and intestinal motility were evaluated before LPS injection (baseline), 6 h after LPS injection (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments. Although the model of synovitis produced clear clinical signs of inflammation, the lameness scores in group C were different from the baseline for only up to 12 h. Both morphine and buprenorphine showed a reduction in the degree of lameness starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more effective analgesic that lasted for more than 12 h and without side effects. It was concluded that morphine would be a valuable analgesic option to alleviate joint pain in the thoracic limbs in ponies.

Objective-To evaluate the effects of subarachnoidally administered hyperbaric morphine, buprenorphine, and methadone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. Animals-6 healthy adult horses. Procedures-Horses were assigned to receive subarachnoid administration of hyperbaric morphine (0.01 mg/kg), buprenorphine (0.001 mg/kg), methadone (0.01mg/kg), or 10% dextrose solution in equal volumes (5 mL). Electrical stimulation was applied every 10 minutes for 60 minutes and every 30 minutes for 120 minutes after subarachnoid injection over the dermatomes of the perineal, sacral, lumbar, and thoracic regions, and the avoidance threshold voltage was recorded. Heart and respiratory rate, blood gas tensions, serum electrolyte concentrations, and sedative effects were also evaluated. Results-Administration of 10% dextrose solution did not change the avoidance threshold. Morphine and methadone significantly increased the avoidance threshold by 10 minutes after injection, which lasted until 120 minutes after subarachnoid administration in the perineal, sacral, lumbar, and thoracic regions. Profound analgesia (avoidance threshold > 40 V) was achieved in all regions. Buprenorphine also significantly increased the avoidance threshold by 10 minutes (36 V) after injection, which lasted 60 minutes and was considered moderate. Heart rate, blood pressure, respiratory rate, and blood gas tensions stayed within reference range. No ataxia, signs of sedation, or CNS excitement were observed. Conclusions and Clinical Relevance-Subarachnoid administration of hyperbaric morphine or methadone produces intense analgesia for 120 minutes over the dermatomes of the perineal, sacral, lumbar, and thoracic areas without cardiorespiratory depression, ataxia, or CNS excitement in horses.

Objective-To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. Animals-12 healthy, female, spayed cats. Procedure-Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. Results-All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. Conclusions and Clinical Relevance-Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.

The hemodynamic effects of 1.5 minimal alveolar concentration of halothane alone (1.6% end-tidal) and 1.5 minimal alveolar concentration of halothane (1.1% end-tidal concentration) combined with epidurally administered morphine were compared during controlled ventilation in 10 dogs used on 2 occasions and randomly allocated to 2 groups. Arterial blood pressure, cardiac index, stroke volume, left ventricular work, and pulmonary arterial pressure were significantly (P < 0.05) higher in dogs of the morphine-treated group before administration of morphine. After epidural administration of morphine (0.1 mg/kg of body weight diluted in 0.26 ml of saline solution/kg), hemodynamic changes were not observed, and the aforementioned variables remained significantly (P < 0.05) higher than values in dogs of the halothane only group. Compared with halothane (1.6%) alone, the reduction in halothane end-tidal concentration (1.1%) associated with epidurally administered morphine is beneficial in maintaining hemodynamic function.

In vitro effects of a mixture of Escherichia coli heat-stable enterotoxins (STa and STb) on isolated jejunum of 3-week-old male pigs were studied, using everted intestinal sac techniques. Heat-stable enterotoxins increased chloride secretion and chloride absorption in everted intestinal sacs. The increase of secretory flux was greater than that for absorptive flux. Vasoactive intestinal peptide (6 x 10-9M) increased chloride secretion, but had no effect on chloride absorption. Neither vasoactive intestinal peptide nor pilocarpine (10-5M) had additive effect to ST. Secretory effects of ST were not blocked by atropine 2 x 10-5M), clonidine (10-6M), or morphine (4.2 X 10-6M).

OBJECTIVE To evaluate the antinociceptive efficacy of IM morphine sulfate or butorphanol tartrate administration in tegus (Salvator merianae). ANIMALS 6 healthy juvenile (12- to 24-month-old) tegus (mean ± SD body weight, 1,484 ± 473 g). PROCEDURES In a crossover study design, tegus were randomly assigned to treatment order, with a minimum washout period of 15 days between treatments. Each of 5 treatments was administered IM in a forelimb: saline (0.9% NaCl) solution (0.5 mL), morphine sulfate (5 or 10 mg/kg), or butorphanol tartrate (5 or 10 mg/kg). A withdrawal latency test was used to evaluate antinociception, with a noxious thermal stimulus applied to the plantar surface of the hind limb before (0 hours; baseline) and 0.5, 1, 2, 3, 4, 6, 12, and 24 hours after each treatment. Observers were unaware of treatment received. RESULTS With saline solution, mean hind limb withdrawal latencies (interval to limb withdrawal from the thermal stimulus) remained constant, except at 12 hours. Tegus had higher than baseline mean withdrawal latencies between 0.5 and 1 hour and at 12 hours with morphine at 5 mg/kg and between 1 and 12 hours with morphine at 10 mg/kg. With butorphanol at 5 and 10 mg/kg, tegus maintained withdrawal responses similar to baseline at all assessment points. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that morphine, but not butorphanol, provided antinociception at 5 and 10 mg/kg in tegus as measured by thermal noxious stimulus testing. These data supported the hypothesis that μ-opioid (but not κ-opioid) receptor agonists provide antinociception in reptiles.