Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery.

OBJECTIVE: To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia. ANIMALS: 3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included. PROCEDURES: Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale-Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment. RESULTS: Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery. CLINICAL RELEVANCE: Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.

Use of a continuous, local infusion of bupivacaine for postoperative analgesia in dogs undergoing total ear canal ablation.

OBJECTIVE: To determine whether addition of a continuous, local infusion of bupivacaine would improve postoperative analgesia in dogs undergoing total ear canal ablation. DESIGN: Randomized controlled trial. ANIMALS: 16 dogs undergoing total ear canal ablation (12 unilaterally and 4 bilaterally with > 1 month between procedures). PROCEDURE: Dogs were randomly allocated to receive morphine (0.25 mg/kg [0.11 mg/lb]) at the end of the procedure (10 procedures) or morphine and a continuous, local infusion of bupivacaine (0.13 to 0.21 mg/kg/h [0.06 to 0.1 mg/lb/h]; 10 procedures). Dogs were observed for 48 hours after surgery. Additional doses of morphine were administered up to every 4 hours in dogs with signs of severe pain. RESULTS: Temperament, sedation, analgesia, and cumulative pain scores were not significantly different between groups any time after surgery. Recovery score was significantly higher for dogs that received bupivacaine than for control dogs 2 hours after extubation but not at any other time. Serum cortisol concentration was not significantly different between groups at any time but, in both groups, was significantly increased at the time of extubation, compared with all other observation times. Total number of additional doses of morphine administered was not significantly different between groups. Bupivacaine was not detected in the plasma of any of the dogs that received the local bupivacaine infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that addition of a continuous, local infusion of bupivacaine did not significantly increase the degree of postoperative analgesia in dogs that underwent total ear canal ablation and were given morphine at the end of surgery.

Transnasal laryngoscopy for the diagnosis of laryngeal paralysis in dogs.

Four dogs with clinical signs of laryngeal paralysis and three normal dogs were evaluated with transnasal laryngoscopy. Six of these dogs subsequently underwent standard laryngoscopy. For transnasal laryngoscopy, a video endoscope was passed through the left nasal passage after intramuscular sedation and topical anesthesia. The laryngeal opening was observed during spontaneous ventilation. Laryngeal paralysis was diagnosed in four dogs and was confirmed with traditional laryngoscopy in three dogs. Normal motion of the arytenoid cartilages was present in the other three dogs; however, two required mechanical stimulation of the laryngeal mucosa for full evaluation. Transnasal laryngoscopy provided a means for diagnosing laryngeal paralysis in dogs without general anesthesia.

Popliteal and mesenteric lymph node injection with methylene blue for coloration of the thoracic duct in dogs.

OBJECTIVE: To describe and compare the time of onset and intensity of thoracic duct coloration after injection of methylene blue into a mesenteric or popliteal lymph node. STUDY DESIGN: Experimental study. ANIMALS: Twenty adult dogs. METHODS: A right tenth intercostal thoracotomy, a right paracostal laparotomy, and an approach to the right popliteal lymph node were performed on each dog. Methylene blue (0.5 mg/kg of a 1% solution, maximum 10 mg) was injected into either a mesenteric (group M, 10 dogs) or popliteal (group P, 10 dogs) lymph node. Thoracic duct color was graded (0 to 3) every 5 minutes for 60 minutes. Statistical analysis was performed on mean thoracic duct color grade data, on number of successful outcomes between groups M and P, and between weight groups. RESULTS: Coloration of the thoracic duct occurred in all group M dogs and 6 group P dogs. Coloration was first recorded 0 to 10 minutes after injection in all dogs and persisted for 60 minutes in 15 dogs. Mean thoracic duct color grade was significantly increased postinjection compared with preinjection at all times in group M. More successful outcomes occurred in group M (P =.03). CONCLUSIONS: Methylene blue injected into mesenteric or popliteal lymph nodes was successful in coloring the thoracic duct, but both mean grade and number of successful outcomes were significantly higher after mesenteric injection. CLINICAL RELEVANCE: Thoracic duct coloration after lymph node injection occurred within 10 minutes and persisted for 60 minutes. This information is useful in planning thoracic duct ligation in cases of chylothorax when observation of the duct is desired. Injection of both lymph node sites was successful, but mesenteric node injection was a more reliable technique.

4-aminopyridine decreases progesterone production by porcine granulosa cells.

BACKGROUND: Ion channels occur as large families of related genes with cell-specific expression patterns. Granulosa cells have been shown to express voltage-gated potassium channels from more than one family. The purpose of this study was to determine the effects of 4-aminopyridine (4-AP), an antagonist of KCNA but not KCNQ channels. METHODS: Granulosa cells were isolated from pig follicles and cultured with 4-AP, alone or in combination with FSH, 8-CPT-cAMP, estradiol 17beta, and DIDS. Complimentary experiments determined the effects of 4-AP on the spontaneously established pig granulosa cell line PGC-2. Granulosa cell or PGC-2 function was assessed by radio-immunoassay of media progesterone accumulation. Cell viability was assessed by trypan blue exclusion. Drug-induced changes in cell membrane potential and intracellular potassium concentration were documented by spectrophotometric determination of DiBAC4(3) and PBFI fluorescence, respectively. Expression of proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) was assessed by immunoblotting. Flow cytometry was also used to examine granulosa cell viability and size. RESULTS: 4-AP (2 mM) decreased progesterone accumulation in the media of serum-supplemented and serum-free granulosa cultures, but inhibited cell proliferation only under serum-free conditions. 4-AP decreased the expression of StAR, the production of cAMP and the synthesis of estradiol by PGC-2. Addition of either 8-CPT-cAMP or estradiol 17beta to serum-supplemented primary cultures reduced the inhibitory effects of 4-AP. 4-AP treatment was also associated with increased cell size, increased intracellular potassium concentration, and hyperpolarization of resting membrane potential. The drug-induced hyperpolarization of resting membrane potential was prevented either by decreasing extracellular chloride or by adding DIDS to the media. DIDS also prevented 4-AP inhibition of progesterone production. CONCLUSION: 4-AP inhibits basal and FSH-stimulated progesterone production by pig granulosa cells via drug action at multiple interacting steps in the steroidogenic pathway. These inhibitory effects of 4-AP on steroidogenesis may reflect drug-induced changes in intracellular concentrations of K+and Cl- as well as granulosa cell resting membrane potential.

Thoracoscopic visualization and ligation of the thoracic duct in dogs.

OBJECTIVE: To develop a technique for thoracoscopic visualization and ligation of the thoracic duct in dogs. STUDY DESIGN: In vivo experimental study. ANIMALS: Five mature, healthy dogs. METHODS: Dogs were normal based on physical examination, negative occult heartworm test, normal complete blood count and biochemical profile, and normal thoracic radiographs. The dogs were anesthetized, and a ventral midline laparotomy was performed for catheterization of a mesenteric lymphatic. Lymphangiography was performed to determine thoracic duct anatomy. Thoracoscopy was performed in the caudal, right hemithorax after single lung intubation or bronchial blockade. At least two 10-mm clips were placed across the thoracic duct in each dog. Lymphangiography was repeated to assess duct ligation. If complete duct occlusion was not achieved, thoracoscopy was repeated for additional clip placement. After surgery the dogs were euthanatized, and necropsies were performed. RESULTS: Lymphangiography showed that multiple branches of the thoracic duct were present in every dog; bilateral thoracic duct branches were most common. Thoracoscopic identification and ligation of the thoracic duct was successful in all five dogs. Two dogs required a second thoracoscopic procedure to completely occlude flow of contrast through the thoracic duct. Surgery time for thoracoscopy averaged 59 plus minus 9.6 minutes. Retroperitoneal contrast accumulation after thoracic duct ligation occurred in two dogs. One dog required bilateral pulmonary ventilation. CONCLUSION: Thoracoscopy can be used to visualize the thoracic duct for ligation in normal dogs. CLINICAL RELEVANCE: Thoracoscopic ligation of the thoracic duct may be a therapeutic option for management of chylothorax in dogs.