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.

Objective—To evaluate the postoperative analgesic effects of epidural administration of morphine and neostigmine, either alone or in combination, in dogs. Animals—30 dogs undergoing orthopedic surgery on a pelvic limb. Procedures—Anesthetic protocols were standardized. At the end of surgery, 10 dogs each received 1 of 3 epidural treatments: morphine (0.1 mg/kg), neostigmine (5 μg/kg), or morphine plus neostigmine (0.1 mg/kg and 5 μg/kg, respectively). Postoperative pain scores and the need for rescue analgesia were evaluated for 24 hours. Results—Pain scores were higher in the neostigmine group, compared with scores for the morphine-neostigmine group, at 2 and 24 hours after surgery and higher in the morphine group than in the morphine-neostigmine group at 2 and 4 hours. During 24 hours, rescue analgesia was provided for 4, 7, and 2 of 10 dogs each in the morphine, neostigmine, and morphine-neostigmine groups, respectively. The number of dogs given rescue analgesia was significantly different among groups at 2, 3, 4, and 6 hours after surgery. Dogs in the morphine and morphine-neostigmine groups had a lower probability of receiving rescue analgesia within 24 hours than did dogs in the neostigmine group. Conclusions and Clinical Relevance—When administered epidurally, morphine alone or in combination with neostigmine provided effective postoperative analgesia in most dogs after orthopedic surgery, whereas neostigmine alone did not. Findings for this study suggested a potential role for neostigmine as an adjuvant for epidural analgesia in dogs undergoing orthopedic surgeries on the pelvic limbs.

Objective: To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain. Animals: 6 healthy adult horses. Procedures: Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variables; intestinal motility; and response to thermal and electrical noxious stimuli. Adverse effects and horse behavior were also recorded. Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid chromatography–mass spectrometry. Results: No significant differences in any variable were evident after saline solution administration. Intravenous and IM administration of morphine resulted in minimal and short-term cardiorespiratory, intestinal motility, and behavioral changes. A decrease in gastrointestinal motility was detected 1 to 2 hours after IM administration of morphine at doses of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1 mg/kg. Morphine administration yielded no change in any horse's response to noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were detected in plasma after IV and IM administration of morphine. Conclusions and Clinical Relevance: Clinically relevant doses of morphine sulfate yielded minimal and short-term behavioral and intestinal motility effects in healthy horses with no signs of pain. Neither dose of morphine affected their response to a noxious stimulus.

Objective—To investigate the effects of acepromazine maleate and morphine on aqueous tear production before, during, and after sevoflurane anesthesia in dogs. Animals—6 mixed-breed dogs. Procedures—In a Latin square study design, dogs underwent IM administration of morphine (1 mg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (0.05 mL/kg), followed by induction and maintenance of anesthesia with sevoflurane for 30 minutes. The protocol was repeated until all dogs had received all treatments, with a minimum of 7 days between anesthetic episodes. Aqueous tear production was measured via Schirmer tear test I before treatment (baseline); before anesthetic induction; 5, 10, 20, and 30 minutes after anesthetic induction; immediately once dogs recovered from anesthesia; and 2 and 10 hours after recovery. Results—Aqueous tear production for all treatments was significantly lower 10, 20, and 30 minutes (but not 5 minutes) after anesthetic induction than at baseline, before anesthetic induction, at recovery, and 2 and 10 hours after recovery. Aqueous tear production was significantly higher after saline solution administration than after morphine administration at the preinduction measurement point and 2 hours after recovery. No other differences were detected among the 3 treatments. Conclusions and Clinical Relevance—Aqueous tear production after anesthesia did not differ significantly from baseline values after any treatment following 30 minutes of sevoflurane anesthesia, suggesting premedication with morphine or acepromazine does not contribute to a decrease in lacrimation in these circumstances.

Objective-To determine whether changes in amplitude of the reflex-evoked muscle action potential (REMP) elicited by noninvasive dental dolorimetry (electrical stimulation of the tooth pulp) in anesthetized dogs may be used to objectively evaluate the effectiveness of IV and intrathecal (IT) administration of morphine. Animals-6 male Beagles that were 2 to 6 years old. Procedure-Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin via the IV and IT routes of administration; however, only results for morphine and saline treatments were reported here. Dogs were anesthetized and prepared for noninvasive dental dolorimetry. After IV or IT administration, electrical stimulation was applied to a tooth, and REMPs of the digastricus muscle were recorded at 5-minute intervals for 60 minutes. To determine differences in REMP amplitude between treatments, a linear regression line was fitted for each dog-treatment combination. Results-The IV administration of morphine significantly inhibited REMP amplitude, compared with IV administration of saline solution. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution. Conclusions and Clinical Relevance-Noninvasive dental dolorimetry in anesthetized dogs has promise as a technique for use in evaluating the analgesic potential of drugs administered IV and IT through evaluation of their effect on REMP amplitude recorded for the digastricus muscle.

Chickens (n = 18), ranging in age from 30 to 50 weeks and in body weight from 1.1 to 2.1 kg, were anesthetized with isoflurane. Ventilation was controlled, and temperature was maintained at 40.1 +/- 1.0 C. The minimal anesthetic concentration (MAC) of isoflurane was determined by use of a bracketing technique based on purposeful movement in response to a toe clamp. After determining isoflurane MAC in triplicate, birds were given a mu-opioid agonist (morphine, n = 9) or a kappa-opioid agonist (U50488H, n = 9). Determination of MAC was repeated after each IV administration of agonist in progressive doses of 0.1, 1.0, and 3.0 mg/kg of body weight. Heart rate and mean arterial blood pressure (MAP) were recorded immediately before and after each injection. Control MAC (mean +/- SEM) was 1.24 +/- 0.05% and 1.05 +/- 0.03% for the mu- and kappa-opioid agonist groups, respectively. Morphine and U50488H caused a dose-dependent decrease in isoflurane MAC in all birds. Reduction of MAC from control (mean +/- SEW) was 15.1 +/- 2.7, 39.7 +/- 3.1, and 52.4 +/- 4.0% after the 3 successive doses of morphine and was 13.3 +/- 3.0, 27.6 +/- 3.3, and 40.8 +/- 3.8% after U50488H was given. Each opioid injection resulted in significant (P less than or equal to 0.05, repeated measures ANOVA) lowering of MAC. Heart rate and MAP did not change significantly (P less than or equal to 0.05, paired Student's t-test) after any dose of opioid. In conclusion, morphine or U50488H decreased isoflurane MAC in dose-dependent manner without significant effect on heart rate and MAP.

Eighteen dogs undergoing lateral thoracotomy at the left fifth intercostal space were randomly assigned to 1 of 3 postoperative analgesic treatment groups of 6 dogs each as follows: group A, morphine, 1.0 mg/kg of body weight, IM; group B, 0.5% bupivacaine, 1.5 mg/kg given interpleurally; and group C, morphine, 1.0 mg/kg given interpleurally. Heart rate, respiratory rate, arterial blood pressure, arterial blood gas tensions, alveolar-arterial oxygen differences, rectal temperature, pain score, and pulmonary mechanics were recorded hourly for the first 8 hours after surgery, and at postoperative hours 12, 24, and 48. These values were compared with preoperative (control) values for each dog. Serum morphine and cortisol concentrations were measured at 10, 20, and 30 minutes, hours 1 to 8, and 12 hours after treatment administration . All dogs had significant decreases in pHa, PaO2, and oxygen saturation of hemoglobin, and significant increases in PaCO2 and alveolar-arterial oxygen differences in the postoperative period, but these changes were less severe in group-B dogs. Decreases of 50% in lung compliance, and increases of 100 to 200% in work of breathing and of 185 to 383% in pulmonary resistance were observed in all dogs after surgery. Increases in work of breathing were lower, and returned to preoperative values earlier in group-B dogs. The inspiratory time-to-total respiratory time ratio was significantly higher in group-B dogs during postoperative hours 5 to 8, suggesting improved analgesia. Blood pressure was significantly lower in group-A dogs for the first postoperative hour. Significant decreases in rectal temperature were observed in all dogs after surgery, and hypothermia was prolonged in dogs of groups A and C. Significant differences in pain score were not observed between treatment groups. Cortisol concentration was high in all dogs after anesthesia and surgery, and was significantly increased in group-B dogs at hours 4 and 8. Significant differences in serum morphine concentration between groups A and C were only observed 10 minutes after treatment administration. In general, significant differences in physiologic variables between groups A and C were not observed. Results of the study indicate that anesthesia and thoracotomy are associated with significant alterations in pulmonary function and lung mechanics. Interpleurally administered bupivacaine appears to be associated with fewer blood gas alterations and earlier return to normal of certain pulmonary function values. Interpleural administration of morphine does not appear to provide any advantages, in terms of analgesia or pulmonary function, compared with its IM administration.

Cardiovascular effects of epidurally administered morphine, a morphine-xylazine combination, and saline solution (control) during isoflurane-maintained anesthesia were assessed in 6 healthy dogs. Anesthesia was induced with isoflurane in O2 and was maintained at 2.0% end-tidal isoflurane concentration. Ventilation was controlled to maintain PaCO2 at 35 to 45 mm of Hg. The dorsal pedal artery was cannulated for measurement of systolic, mean, and diastolic pressures, and for blood sample collection. Arterial blood pH and gas tensions were determined every 30 minutes. Cardiac output was determined by thermodilution. The ECG, heart rate, body temperature, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal isoflurane concentration, and CO2 tension were monitored. Systemic and pulmonary vascular resistance, arterial HCO3(-) concentration, base excess, and cardiac index were calculated. After baseline measurements were taken, morphine (0.1 mg/kg of body weight) in 5 ml of isotonic saline solution, morphine and xylazine (0.1 mg of morphine and 0.09 mg of xylazine/kg) in 5 ml of isotonic saline solution, or 5 ml of isotonic saline solution was injected into the lumbosacral epidural space. Data were recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Statistical analysis included ANOVA for repeated measures. Significance was set at P < 0.05. None of the measured variables was significantly different among the 3 treatments at any time. Results of the study indicated that epidural administration of morphine or morphine and xylazine is not associated with significant cardiovascular side effects during isoflurane-maintained anesthesia in dogs.

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).