OBJECTIVE To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. ANIMALS 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. PROCEDURES 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and prostaglandin E metabolites) served as indicators of COX activity, and serum drug concentrations were measured by use of high-performance liquid chromatography. An in vitro coagulation-induced thromboxane B2 assay was used to calculate drug concentration-COX-1 inhibition curves. Effect of time and treatment on COX activity was determined. Agreement between in vitro and ex vivo measurement of COX activity was assessed with Bland-Altman analysis. RESULTS At 2 and 24 hours after NSAID administration, COX-1 activity was reduced, compared with baseline activity, for the flunixin meglumine group only and relative COX-1 activity was significantly greater for the firocoxib group, compared with that for the flunixin meglumine group. There was no significant change in COX-2 activity after surgery for either group. Bland-Altman analysis revealed poor agreement between in vitro and ex vivo measurement of COX-1 activity. CONCLUSIONS AND CLINICAL RELEVANCE Compared with flunixin meglumine, firocoxib had COX-1-sparing effects ex vivo in equine patients that underwent elective surgery.

OBJECTIVE To determine effects of increasing plasma fentanyl concentrations on the minimum alveolar concentration (MAC) of isoflurane in rabbits. ANIMALS 6 adult female New Zealand White rabbits (Oryctolagus cuniculus). PROCEDURES Rabbits were anesthetized with isoflurane in oxygen; ventilation was controlled and body temperature maintained between 38.5° and 39.5°C. Fentanyl was administered IV by use of a computer-controlled infusion system to achieve 6 target plasma concentrations. Isoflurane MAC was determined in duplicate by use of the bracketing technique with a supramaximal electrical stimulus. Blood samples were collected for measurement of plasma fentanyl concentration at each MAC determination. The MAC values were analyzed with a repeated-measures ANOVA followed by Holm-Sidak pairwise comparisons. RESULTS Mean ± SD plasma fentanyl concentrations were 0 ± 0 ng/mL (baseline), 1.2 ± 0.1 ng/mL, 2.2 ± 0.3 ng/mL, 4.4 ± 0.4 ng/mL, 9.2 ± 0.4 ng/mL, 17.5 ± 2.6 ng/mL, and 36.8 ± 2.4 ng/mL. Corresponding mean values for isoflurane MAC were 1.92 ± 0.16%, 1.80 ± 0.16%, 1.60 ± 0.23%, 1.46 ± 0.22%, 1.12 ± 0.19%, 0.89 ± 0.14%, and 0.70 ± 0.15%, respectively. Isoflurane MAC for plasma fentanyl concentrations ≥ 2.2 ng/mL differed significantly from the baseline value. In 3 rabbits, excessive spontaneous movement prevented MAC determination at the highest plasma fentanyl concentration. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl reduced isoflurane MAC by approximately 60% in New Zealand White rabbits. Further studies will be needed to investigate the cardiorespiratory effects of isoflurane and fentanyl combinations in rabbits; however, fentanyl may prove to be a useful adjunct to inhalation anesthesia in this species.

This study investigated the analgesic and systemic effects of intramuscular (IM) versus epidural (EP) administration of tramadol as an adjunct to EP injection of lidocaine in cats. Six healthy, domestic, shorthair female cats underwent general anesthesia. A prospective, randomized, crossover trial was then conducted with each cat receiving the following 3 treatments: EP injection of 2% lidocaine [LEP; 3.0 mg/kg body weight (BW)]; EP injection of a combination of lidocaine and 5% tramadol (LTEP; 3.0 and 2.0 mg/kg BW, respectively); or EP injection of lidocaine and IM injection of tramadol (LEPTIM; 3.0 and 2.0 mg/kg BW, respectively). Systemic effects, spread and duration of analgesia, behavior, and motor blockade were determined before treatment and at predetermined intervals afterwards. The duration of analgesia was 120 ± 31 min for LTEP, 71 ± 17 min for LEPTIM, and 53 ± 6 min for LEP (P < 0.05; mean ± SD). The cranial spread of analgesia obtained with LTEP was similar to that with LEP or LEPTIM, extending to dermatomic region T13–L1. Complete motor blockade was similar for the 3 treatments. It was concluded that tramadol produces similar side effects in cats after either EP or IM administration. Our findings indicate that EP and IM tramadol (2 mg/kg BW) with EP lidocaine produce satisfactory analgesia in cats. As an adjunct to lidocaine, EP tramadol provides a longer duration of analgesia than IM administration. The adverse effects produced by EP and IM administration of tramadol were not different. Further studies are needed to determine whether EP administration of tramadol could play a role in managing postoperative pain in cats when co-administered with lidocaine after painful surgical procedures.

OBJECTIVE To evaluate pharmacokinetics of ammonium tetrathiomolybdate (TTM) after IV and oral administration to dogs and effects of TTM administration on trace mineral concentrations. ANIMALS 8 adult Beagles and Beagle crossbreds (4 sexually intact males and 4 sexually intact females). PROCEDURES Dogs received TTM (1 mg/kg) IV and orally in a randomized crossover study. Serum molybdenum and copper concentrations were measured via inductively coupled plasma mass spectrometry in samples obtained 0 to 72 hours after administration. Pharmacokinetics was determined via noncompartmental analysis. RESULTS For IV administration, mean ± SD terminal elimination rate constant, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 4.9 ± 0.6 μg/mL, 30.7 ± 5.4 μg/mL•h, and 27.7 ± 6.8 hours, respectively. For oral administration, mean ± SD terminal elimination rate constant, time to maximum concentration, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 3.0 ± 3.5 hours, 0.2 ± 0.4 μg/mL, 6.5 ± 8.0 μg/mL•h, and 26.8 ± 8.0 hours, respectively. Oral bioavailability was 21 ± 22%. Serum copper concentrations increased significantly after IV and oral administration. Emesis occurred after IV (2 dogs) and oral administration (3 dogs). CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetics for TTM after a single IV and oral administration was determined for clinically normal dogs. Absorption of TTM after oral administration was variable. Increased serum copper concentrations suggested that TTM mobilized tissue copper. Further studies will be needed to evaluate the potential therapeutic use of TTM in copper-associated chronic hepatitis of dogs.

OBJECTIVE To compare the characteristics and multipotential and in vivo cartilage formation capabilities of porcine adipose-derived stem cells (pASCs) with those of porcine skin-derived stem cell–like cells (pSSCs). ANIMALS Three 6-month-old female pigs and four 6-week-old female athymic mice. PROCEDURES Adipose and skin tissue specimens were obtained from each pig following slaughter and digested to obtain pASCs and pSSCs. For each cell type, flow cytometry and reverse transcription PCR assays were performed to characterize the expression of cell surface and mesenchymal stem cell markers, and in vitro cell cultures were performed to determine the adipogenic, osteogenic, and chondrogenic capabilities. Each cell type was then implanted into athymic mice to determine the extent of in vivo cartilage formation after 6 weeks. RESULTS The cell surface and mesenchymal stem cell marker expression patterns, multipotential capability, and extent of in vivo cartilage formation did not differ significantly between pASCs and pSSCs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that pSSCs may be a viable alternative to pASCs as a source of progenitor cells for tissue engineering in regenerative medicine.

The objective of this study was to examine the effect of calving difficulty or dystocia on the vitality of newborn calves and its association with blood pH, the apparent efficiency of immunoglobulin G (IgG) absorption (AEA), and weight gain. A total of 45 calving events (N = 48 calves) were monitored from the first sight of fetal membranes. All calves were assessed at the time of first attaining sternal recumbency (SR), at 2 and 24 h, and at 7 and 14 d of age. Measurements included time to SR, rectal temperature, respiration and heart rate, analysis of blood gases and other blood measures, suckling response, time to standing, passive transfer of IgG, and weight gain. Calves were separated from their dam 2 h after birth and fed a commercial colostrum replacer containing 180 g of IgG by esophageal tube feeder. Calves born following dystocia had lower venous blood pH and took longer to attain SR and attempt to stand than those born unassisted. Duration of calving interacted with the number of people required to extract the calf by pulling as a significant predictor of pH at SR. No association was found between pH at SR and AEA. However, reduced AEA was found in calves that were female and in calves that did not achieve SR within 15 min of birth. A longer calving duration, being born in July or August rather than June, and a shorter time spent standing in the first 2 d of life were significantly associated with reduced weight gain to 14 d. It was concluded that factors at calving impact the physiology, vitality, and subsequent weight gain of newborn calves.

OBJECTIVE To determine effects of equipotent concentrations of fentanyl and isoflurane, compared with isoflurane alone, on cardiovascular variables in New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS 6 adult female New Zealand White rabbits. PROCEDURES Rabbits were anesthetized with isoflurane, and lungs were mechanically ventilated. The minimum alveolar concentration (MAC) of isoflurane alone (baseline) and with fentanyl administered IV to achieve 3 targeted plasma concentrations was determined for each rabbit by means of an electrical stimulus. Cardiovascular variables were measured in a separate experiment at 1.3X isoflurane MAC and equipotent doses of isoflurane plus fentanyl at the same 3 targeted plasma concentrations. Blood samples were collected for measurement of blood gas variables and plasma fentanyl concentrations. Treatment effects were evaluated by repeated-measures ANOVA followed by 2-tailed paired t tests with sequentially rejective Bonferroni correction. RESULTS Mean ± SD MAC of isoflurane was 1.95 ± 0.27%. Mean measured plasma fentanyl concentrations of 4.97, 8.93, and 17.19 ng/mL reduced isoflurane MAC by 17%, 37%, and 56%, respectively. Mean measured plasma fentanyl concentrations during cardiovascular measurements were 5.49, 10.26, and 18.40 ng/mL. Compared with baseline measurements, heart rate was significantly lower at all 3 plasma fentanyl concentrations, mean arterial blood pressure and systemic vascular resistance were significantly higher at mean fentanyl concentrations of 10.26 and 18.40 ng/mL, and cardiac output was significantly higher at 18.40 ng of fentanyl/mL. CONCLUSIONS AND CLINICAL RELEVANCE Administration of fentanyl in isoflurane-anesthetized rabbits resulted in improved mean arterial blood pressure and cardiac output, compared with isoflurane alone. This balanced anesthesia technique may prove useful in the management of clinical cases in this species.