The effect of hypercapnia on the arrhythmogenic dose of epinephrine (ADE) was investigated in 14 horses. Anesthesia was induced with guaifenesin and thiamylal sodium and was maintained at an end-tidal halothane concentration between 0.86 and 0.92%. Base-apex ECG, cardiac output, and facial artery blood pressure were measured and recorded. The ADE was determined at normocapnia (arterial partial pressure of carbon dioxide [Pa(CO2)] = 35 to 45 mm of Hg), at hypercapnia (Pa(CO2) = 70 to 80 mm of Hg), and after return to normocapnia. Epinephrine was infused at arithmetically spaced increasing rates (initial rate = 0.25 micrograms/kg of body weight/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate, to the nearest 0.25 micrograms/kg/min, at which 4 premature ventricular complexes occurred in a 15-second period. The ADE (mean +/- SD) during hypercapnia (1.04 +/- 0.23 micrograms/kg/min) was significantly (P < 0.05) less than the ADE at normocapnia (1.35 +/- 0.38 micrograms/kg/min), whereas the ADE after return to normocapnia (1.17 +/- 0.22 micrograms/kg/min) was not significantly different from those during normocapnia or hypercapnia. Baseline systolic and diastolic arterial pressures and cardiac output decreased after return to normocapnia. Significant differences were not found in arterial partial pressure of O2 (Pa(O2)) or in base excess during the experiment. Two horses developed ventricular fibrillation and died during normocapnic determinations of ADE. Hypercapnia was associated with an increased risk of developing ventricular arrhythmias in horses anesthetized with guaifenesin, thiamylal sodium, and halothane.

OBJECTIVE To determine the in vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in blood from healthy dogs. SAMPLES Blood samples from 9 healthy dogs. PROCEDURES Blood samples were incubated with LPS from Escherichia coli O127:B8 or PBSS (control) for 1 hour. Afterward, the samples were incubated with 10μM epinephrine, norepinephrine, or dobutamine or with saline (0.9% NaCl) solution (control) for 23 hours. Leukocyte viability was assessed by use of trypan-blue exclusion in blood from 2 dogs to ensure cell viability was not altered by the catecholamines. Tumor necrosis factor-α, IL-6, and IL-10 concentrations were measured in the supernatant in duplicate with a canine-specific multiplex bead-based assay. Blood samples from 2 dogs were used to create dose-response curves to evaluate whether the observed cytokine modulation was dependent on catecholamine concentration. RESULTS Incubation of blood with epinephrine and norepinephrine significantly increased LPS-stimulated production of IL-10, compared with the control. Epinephrine and norepinephrine significantly decreased LPS-stimulated production of TNF-α, compared with the control. Epinephrine and norepinephrine did not significantly alter LPS-stimulated production of IL-6. Dobutamine did not alter catecholamine production. CONCLUSIONS AND CLINICAL RELEVANCE Epinephrine and norepinephrine, but not dobutamine, had immunomodulatory effects on LPS-stimulated TNF-α and IL-10 production in blood from healthy dogs in this in vitro model of sepsis. Data suggested that dobutamine may have immune system-sparing effects in dogs with sepsis.

OBJECTIVE To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets. SAMPLE Blood samples from 12 healthy adult cats. PROCEDURES In 7 experiments, the effects of 23 imidazoline and nonimidazoline α-adrenoceptor agonists or antagonists on aggregation and antiaggregation of feline platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation. RESULTS Platelet aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline induced a dose-dependent potentiation of ADP- or collagen-induced aggregation. Oxymetazoline and xylometazoline also induced a small potentiation of ADP-stimulated aggregation, but other α-adrenoceptor agonists did not induce potentiation. The α2-adrenoceptor antagonists and certain imidazoline α-adrenergic agents including phentolamine, yohimbine, atipamezole, clonidine, medetomidine, and dexmedetomidine inhibited adrenaline-potentiated aggregation induced by ADP or collagen in a dose-dependent manner. The imidazoline compound antazoline inhibited adrenaline-potentiated aggregation in a dose-dependent manner. Conversely, α1-adrenoceptor antagonists and nonimidazoline α-adrenergic agents including xylazine and prazosin were ineffective or less effective for inhibiting adrenaline-potentiated aggregation. Moxonidine also was ineffective for inhibiting adrenaline-potentiated aggregation induced by collagen. Medetomidine and xylazine did not reverse the inhibitory effect of atipamezole and yohimbine on adrenaline-potentiated aggregation. CONCLUSIONS AND CLINICAL RELEVANCE Adrenaline-potentiated aggregation of feline platelets may be mediated by α2-adrenoceptors, whereas imidazoline agents may inhibit in vitro platelet aggregation via imidazoline receptors. Imidazoline α-adrenergic agents may have clinical use for conditions in which there is platelet reactivity to adrenaline. Xylazine, medetomidine, and dexmedetomidine may be used clinically in cats with minimal concerns for adverse effects on platelet function.

OBJECTIVE To determine whether addition of epinephrine to a lidocaine solution would prolong and potentiate the efficacy of a palmar digital nerve block (PDNB) in horses. ANIMALS 6 adult horses with naturally occurring forefoot lameness. PROCEDURES Initially, a PDNB with a 2% lidocaine solution was performed on the affected foot of each horse. Three days later, the PDNB was repeated with a 1% lidocaine solution or a 1% lidocaine solution containing epinephrine (dilution, 1:200,000). After another 3-day washout period, the PDNB was repeated with the treatment opposite that administered for the second PDNB. Gait was analyzed with a computerized lameness analysis system and heart rate and extent of skin sensation between the heel bulbs of the blocked foot were evaluated at predetermined times for 2 hours after each PDNB. RESULTS Efficacy and duration of the PDNB did not differ significantly between the 2% and 1% lidocaine treatments. The addition of epinephrine to the 1% lidocaine solution improved the efficacy and prolonged the duration of the PDNB. It also resulted in a positive correlation between skin desensitization and amelioration of lameness. Median heart rate remained unchanged throughout the observation period for all 3 treatments. No adverse effects associated with the PDNBs were observed. CONCLUSIONS AND CLINICAL RELEVANCE Addition of epinephrine (dilution, 1:200,000) to a 1% lidocaine solution improved the efficacy and prolonged the duration of a PDNB in horses with naturally occurring lameness and might be clinically useful for lameness evaluations and standing surgery of the forefoot of horses.

The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO3 per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb’s LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 μm) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb.

The effects of short-term restraint stress, by means of snaring, on plasma concentrations of catecholamines, beta-endorphin, and cortisol were studied in 6 gilts. A catheter was inserted into the jugular vein, and 2 blood samples were collected before onset of stress. Thereafter, a hog snare was applied, and blood samples were collected at 0.5, 2, and 3.5 minutes after the start of snaring. Plasma epinephrine and norepinephrine concentrations increased (P < 0.001) within 0.5 minute after start of restraint and decreased thereafter. Plasma concentration of beta-endorphin increased (P < 0.05) within 2 minutes after start of restraint, whereas that of cortisol increased (P < 0.05) 3.5 minutes after start of restraint. Taken together, short-term stress, such as snaring, may increase the plasma concentration of catecholamines, beta-endorphin, and cortisol in pigs.

Plasma catecholamine concentrations in response to onychectomy were examined in 27 cats receiving different anesthetic regimens. Each cat was anesthetized with a dissociative-tranquilizer combination, and onychectomy was performed on 1 forefoot. One week later, each cat was anesthetized with the same dissociative-tranquilizer combination plus either butorphanol or oxymorphone, and onychectomy was performed on the other forefoot. Four treatment groups were studied: tiletamine-zolazepam and tiletamine-zolazepam-butorphanol combinations were administered to group-1 cats, ketamine-acepromazine and ketamine-acepromazine-butorphanol combinations were administered to group-2 cats, tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone combinations were administered to group-3 cats, and ketamine-acepromazine and ketamine-acepromazine-oxymorphone combinations were administered to group-4 cats. All drug combinations were administered IM. Central venous blood samples were drawn for catecholamine analysis after injection of drug(s), after onychectomy, and 1, 2, and 4 hours after injection. Tiletamine-zolazepam alone or tiletamine-zolazepam-butorphanol prevented epinephrine release for 2 hours after injection of drug(s). Norepinephrine concentration increased significantly (P < 0.05) from baseline after onychectomy for tiletimine-zolazepam-butorphanol and at 4 hours for tiletamine-zolazepam and tiletamine-zolazepambutorphanol. After onychectomy, there was no difference in epinephrine values between tfletamine-zolazepam and tiletamine-zolazepam-oxymorphone. Ketamine-acepromazine prevented increases in norepinephrine and epinephrine concentrations for up to 2 hours after surgery. Addition of butorphanol to ketamine-acepromazine decreased norepinephrine values immediately after onychectomy. Addition of oxymorphone to ketamine-acepromazine resulted in lower epinephrine values 4 hours after surgery.

The effect of hypercapnia on the arrhythmogenic dose of epinephrine (ADE) was investigated in 14 horses. Anesthesia was induced with guaifenesin and thiamylal sodium and was maintained at an end-tidal halothane concentration between 0.86 and 0.92%. Base-apex ECG, cardiac output, and facial artery blood pressure were measured and recorded. The ADE was determined at normocapnia (arterial partial pressure of carbon dioxide [Pa(CO2)] = 35 to 45 mm of Hg), at hypercapnia (Pa(CO2) = 70 to 80 mm of Hg), and after return to normocapnia. Epinephrine was infused at arithmetically spaced increasing rates (initial rate = 0.25 micrograms/kg of body weight/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate, to the nearest 0.25 micrograms/kg/min, at which 4 premature ventricular complexes occurred in a 15-second period. The ADE (mean +/- SD) during hypercapnia (1.04 +/- 0.23 micrograms/kg/min) was significantly (P < 0.05) less than the ADE at normocapnia (1.35 +/- 0.38 micrograms/kg/min), whereas the ADE after return to normocapnia (1.17 +/- 0.22 micrograms/kg/min) was not significantly different from those during normocapnia or hypercapnia. Baseline systolic and diastolic arterial pressures and cardiac output decreased after return to normocapnia. Significant differences were not found in arterial partial pressure of O2 (Pa(O2)) or in base excess during the experiment. Two horses developed ventricular fibrillation and died during normocapnic determinations of ADE. Hypercapnia was associated with an increased risk of developing ventricular arrhythmias in horses anesthetized with guaifenesin, thiamylal sodium, and halothane.