Effects of pre-operative administration of medetomidine on plasma insulin and glucose concentrations in healthy dogs and dogs with insulinoma.

OBJECTIVE: To investigate the effect of medetomidine on plasma glucose and insulin concentrations in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery. ANIMALS: Twenty-five dogs with insulinoma and 26 healthy dogs. METHODS: In dogs with insulinoma, medetomidine (5 µg kg(-1) ) was randomly included (n = 12) or omitted (n = 13) from the pre-anesthetic medication protocol, which typically contained an opioid and an anticholinergic. Healthy dogs received medetomidine (5 µg kg(-1) ; n = 13) or acepromazine (0.04 mg kg(-1) ; n = 13) plus an opioid (morphine 0.5 mg kg(-1) ) and an anticholinergic (atropine 0.04 mg kg(-1) ) as pre-anesthetic medications. Pre-anesthetic medications were given intramuscularly. Plasma glucose and insulin concentrations were measured before (sample 1) and 30 minutes after pre-anesthetic medication (sample 2), and at the end of surgery in dogs with insulinoma or at 2 hours of anesthesia in healthy dogs (sample 3). Glucose requirement to maintain intra-operative normoglycemia in dogs with insulinoma was quantified and compared. Data were analyzed with anova and Bonferroni post-test, t-tests or chi-square tests as appropriate with p < 0.05 considered significant. Data are shown as mean ± SD. RESULTS: Medetomidine significantly decreased plasma insulin concentrations and increased plasma glucose concentrations in healthy dogs and those with insulinoma. These variables did not change significantly in the dogs not receiving medetomidine. In the dogs with insulinoma, intra-operative glucose administration rate was significantly less in the animals that received medetomidine compared to those that did not. CONCLUSIONS: Pre-anesthetic administration of medetomidine significantly suppressed insulin secretion and increased plasma glucose concentration in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery. CLINICAL RELEVANCE: These findings support the judicious use of medetomidine at low doses as an adjunct to the anesthetic management of dogs with insulinoma.

Potential role of the CD38/cADPR signaling pathway as an underlying mechanism of the effects of medetomidine on insulin and glucose homeostasis.

OBJECTIVE: To investigate the CD38/cADPR signaling pathway as possible underlying mechanism of the effects of medetomidine on insulin and glucose homeostasis. ANIMALS: Thirty-two C57BL/6 mice of both sexes. METHODS: Wild-type (WT) and CD38-knockout (CD38(-/-) ) mice received medetomidine (50 µg kg(-1) ) or a similar volume of 0.9% NaCl (control) by intraperitoneal (IP) injection (each group n = 8). The mice were euthanized 45 minutes later with sodium pentobarbital IP and blood was sampled via cardiac puncture. Insulin and glucose concentrations were measured by radioimmunoassay and by the oxygen rate method, respectively. Data were analyzed with anova and Bonferroni post hoc (5% significance) and are shown as mean ± SD. RESULTS: Plasma insulin and glucose concentrations were similar between WT and CD38(-/-) mice under control conditions. As compared to controls, medetomidine administration produced a statistically significant decrease in plasma insulin concentrations in the WT mice whereas the decrease in the CD38(-/-) mice was not statistically significant. Correspondingly, medetomidine caused a significantly greater increase in plasma glucose concentrations in the WT than in the CD38(-/-) mice. CONCLUSION: The CD38/cADPR signaling pathway may be one underlying mechanism of the glucose and insulin effects of the alpha-2 adrenergic receptor agonist medetomidine and likely other drugs of its class.

Effects of preoperative epidural administration of racemic ketamine for analgesia in sheep undergoing surgery.

OBJECTIVE: To investigate the effects of preoperative epidural administration of racemic ketamine to provide analgesia in sheep undergoing experimental hind limb orthopedic surgery. ANIMALS: 12 adult sheep (weight range, 51.4 to 67.2 kg). PROCEDURE: Sheep were anesthetized with guaifenesin, thiopental, and isoflurane; after induction of anesthesia, sheep received a lumbosacral epidural injection of ketamine (1 mg/kg; n = 6) or saline (0.9% NaCl) solution (1 mL/7 kg; 6 [control group]). Respiratory and cardiovascular variables were recorded before and at intervals during and for 6 hours after anesthesia. During that 6-hour postoperative period, analgesia was evaluated subjectively with a numeric ranking scale that included assessments of comfort, posture, movement, and response to wound palpation; buprenorphine was administered when a score > 3 (maximum score, 10) was achieved. Rectal temperature, heart and respiratory rates, and lameness were evaluated daily for 2 weeks after surgery. RESULTS: At all evaluations, cardiovascular and respiratory variables were comparable between the 2 groups. Compared with control sheep, time to first administration of rescue analgesic was significantly longer and total dose of buprenorphine administered during the 6- hour postoperative period was significantly decreased for ketamine-treated sheep. During the second week following surgery, ketamine-treated sheep had significantly less lameness than control sheep. CONCLUSIONS AND CLINICAL RELEVANCE: In sheep undergoing hind limb surgery, preoperative epidural administration of ketamine appears to provide analgesia in the immediate postoperative period and has residual analgesic effects, which may contribute to more rapid return of normal function in surgically treated limbs.

Evaluation of histamine release during constant rate infusion of morphine in dogs.

OBJECTIVE: To evaluate histamine release and selected physiologic variables during constant rate infusion (CRI) of morphine in dogs. ANIMALS: Five healthy, conscious, intact female dogs. MATERIAL AND METHODS: Using a Latin square, repeated-measures design, dogs were randomly assigned to three treatment groups to receive a 4-hour CRI of saline (SAL), or a loading dose of morphine at 0.3 mg kg(-1) (LM), or 0.6 mg kg(-1) (HM), followed by an infusion of 0.17 mg kg(-1) hour(-1) (LM) and 0.34 mg kg(-1) hour(-1) (HM) respectively. Dogs received each of the three treatments at intervals of at least 7 days. Plasma histamine concentration, skin flushing, edema and wheals, heart rate and rhythm and non-invasive arterial blood pressure were measured before the loading dose and at 1, 2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI, or at the time of occurrence. RESULTS: The loading dose induced the highest histamine release in the HM group being statistically higher than the SAL group. The histamine release obtained in the LM group after the loading dose did not differ from SAL. During the infusion, plasma histamine levels were numerically higher in the LM group. Besides one dog that developed hypotension for 2 minutes after the loading dose in the HM group and one dog that showed occasional ventricular premature contractions during both morphine infusions, cardiovascular variables were similar among the three treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of morphine induced variable histamine release with minimal adverse cardiovascular effects in these conscious, healthy dogs. The plasma histamine levels obtained may be associated with significant hemodynamic changes in patients with limited cardiovascular reserve and sympathetic nervous tone.