Results of 24-hour ambulatory electrocardiography in dogs undergoing ovariohysterectomy following premedication with medetomidine or acepromazine

OBJECTIVE: To investigate heart rate characteristics in dogs undergoing ovariohysterectomy following premedication with medetomidine or acepromazine. DESIGN: Clinical trial. ANIMALS: 43 client-owned dogs. PROCEDURE: 24-hour ambulatory electrocardiography was performed beginning approximately 1 hour prior to administration of premedications. Dogs were premedicated with medetomidine and butorphanol (n = 21) or acepromazine and butorphanol (22) and, approximately 85 minutes later, were anesthetized with propofol and isoflurane. Electrocardiographic recordings were examined to determine heart rate, cardiac conduction disturbances (ventricular premature complexes and atrioventricular block), and indices of heart rate variability (HRV). RESULTS: Minimum heart rate during the 24-hour recording period was significantly lower among dogs given medetomidine than among dogs given acepromazine, but during the postoperative period, heart rate increased in all dogs as they became physically active. Intraoperative time domain HRV indices were lower and the low frequency-to-high frequency ratio was higher among dogs given acepromazine than among dogs given medetomidine; however, significant differences between groups were no longer seen by 6 hours after surgery. There was no significant difference between groups with regard to the number of ventricular premature complexes or to values of scaling exponent alpha2 (a nonlinear measure of HRV). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there are greater enhancements in vagally related heart rate indices in medetomidine-treated dogs that may persist until 6 hours after surgery. Despite the low heart rates, dogs given medetomidine showed expected responses to surgery and positional stimuli, and the 2 preanesthetic protocols may not result in different prevalences of ventricular premature complexes.     

Correlation between serum concentrations following continuous intravenous infusion of dexmedetomidine or medetomidine in cats and their sedative and analgesic effects

Dexmedetomidine (DEX) may have some therapeutic advantages over the racemate medetomidine (MED). Here we have examined how serum concentrations of DEX correlate with some of its anaesthetic effects. Cats (n = 6) were administered with a continuous stepwise intravenous (i.v.) infusion of DEX or MED on different occasions in a cross-over design. Maintenance infusion rates (mg/kg/min) used were: DEX = 0.25 (MED = 0.50); DEX = 1 (MED = 2) and DEX = 4 (MED = 8) for infusion steps 1, 2 and 3, respectively. Each maintenance infusion lasted at least 50 min and was preceded with a loading dose. There was no significant difference between serum DEX and 0.5 serum MED concentrations at any dose level nor was there a significant difference between serum DEX and the (entire) serum MED concentrations. There was no significant difference between DEX and MED for sedation, analgesia, muscular relaxation and heart and respiratory rates. For both DEX and MED, serum drug concentration and analgesia were dose-dependent and sedation increased until the end of infusion step 2 (dose level 2) and decreased at the end of step 3 (dose level 3). Muscular relaxation was not dose-dependent. We conclude that increasing the blood concentration of DEX or MED beyond a certain level decreases the level of sedation instead of increasing it even though analgesia increases. The rate at which DEX and MED are metabolized in cats may not be the same.     

Some factors influencing the level of clinical sedation induced by medetomidine in rabbits

Rabbits (n=23) received intravenous bolus medetomidine at 100 mug/kg. Prior to medetomidine administration, heart and respiratory rates were measured, arterial blood was collected and analysed for plasma cortisol, glucose and albumin concentrations. Fifteen minutes after medetomidine administration, heart and respiratory rates were measured again and sedation was scored. The rabbit was afterwards anaesthetized with 20 mg/kg ketamine administered intravenously to enable spinal tap and heart puncture. Cerebrospinal fluid (CSF) was collected (this occurred 20 min post medetomidine administration) and analysed for medetomidine concentration. Blood was collected by heart puncture immediately after the spinal tap and analysed for serum medetomidine concentration. Cerebrospinal fluid medetomidine concentration correlated negatively with sedation. Serum medetomidine correlated positively with CSF medetomidine concentration. Cerebro-spinal fluid medetomidine was 17 +/- 13% of serum medetomidine concentration. Plasma cortisol and glucose concentrations correlated negatively with serum medetomidine. We conclude that after an intravenous bolus administration of a low sedative dose of medetomidine to rabbits; CSF concentration of the drug correlate negatively with sedation and that this may be because of the fact that only the free and unbound medetomidine may be available for detection in the CSF, the concentration of medetomidine detected in the CSF was much lower than that in blood and a positive correlation exists between CSF and serum medetomidine concentrations. Stress may have some effect on the distribution or metabolism of medetomidine in rabbits.     

Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs

Objective

We determined the possible effects of a peripherally acting α₂-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) coadministered medetomidine, butorphanol and midazolam.

Behavioral alterations and severity of pain in cats recovering at home following elective ovariohysterectomy or castration

OBJECTIVE: To identify behavioral alterations in client-owned cats recovering at home following elective ovariohysterectomy or castration and determine owner perceptions regarding severity of postoperative pain. DESIGN: Cohort study. Animals-145 cats undergoing elective ovariohysterectomy (n = 80) or castration (65) at 4 veterinary clinics in Finland. PROCEDURES: Owners were asked to complete a questionnaire on their cats' behavior during the 3 days after surgery. Owners were also asked to indicate their perceptions of the severity of postoperative pain during these days by use of a 100-mm visual analog scale. RESULTS: Owners consistently indicated that there were changes in their cats' behavior, with the most commonly reported alterations being a decrease in overall activity level, an increase in the amount of time spent sleeping, a decrease in playfulness, and altered way of movement. Changes (ie, either an increase or decrease) in aggressive behavior were rare. Median pain score the day of surgery was 15.0 mm for male cats and 25.0 mm for female cats. Behavior score was significantly associated with day of observation, type of surgery (ovariohysterectomy vs castration), owner-assigned pain score, and veterinary clinic. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that behavioral alterations can be detected for several days after surgery in cats recovering at home following ovariohysterectomy or castration and emphasized owner concerns about the existence of postoperative pain.     

Characterization of Oat Endoproteinases that Hydrolyze Oat Avenins

During oat seed germination, the insoluble storage proteins must be solubilized and transported to the embryo for use by the developing plantlet. We showed earlier that pH 6.2 active serine and metalloproteinases were the predominant gelatin‐hydrolyzing enzymes of oats, while the oat globulins were degraded by pH 3.8 active cysteine proteases. The pH of the endosperms of germinating oats is 6.2. We have continued our characterization of the germinated oat proteinases by determining which hydrolyze avenins, the oat storage prolamins. Avenins of resting seeds were purified and hydrolyzed with proteinases that were extracted from oat seeds that were germinated for various periods. The peptides released were analyzed using SDS‐PAGE. The α‐avenins were hydrolyzed at pH 3.8 by cysteine proteinases from four‐day germinated seeds and the β‐avenins were hydrolyzed by similar enzymes from eight‐day germinated seeds. At pH 6.2 or pH 5.0, the avenins were not degraded by any of the germinated oats endoproteinases. It is probable that some kind of pH compartmentalization occurs within germinating oat seed. After four days of germination, either new proteinases form or some preexisting proteinases are activated. The cysteine proteinases are apparently responsible for the majority of the storage protein hydrolysis that occurs during oat germination.     

Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.

The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedation reaching steady state plasma medetomidine levels of 1-1.5 ng ml(-1)within 30 minutes. Sedation was reversed effectively by atipamezole (60 mcg kg(-1)) i.v. The pharmacokinetics of medetomidine make it suitable for prolonged use by infusion, such as is required as part of a total intravenous anaesthetic technique in horses.     

Hemodynamic effects of an intravenous infusion of medetomidine at six different dose regimens in isoflurane-anesthetized dogs

This study investigated the dose dependency of the hemodynamic effects of IV medetomidine (MED) constant-rate infusion (CRI) during isoflurane anesthesia. Twenty-four healthy beagles randomly received one of six MED CRI regimens. A loading dose of MED was administered IV at 0.2, 0.5, 1.0, 1.7, 4.0, or 12.0 ug/kg-1 for 10 minutes, followed by a maintenance CRI providing identical dose amounts over 60 minutes. Heart rate and mean arterial blood pressure were recorded, blood gases were analyzed, and cardiac index (CI) was determined. Statistical analysis involved a repeated measures linear model. Baseline CI demonstrated a dose-dependent decrease as the MED dose increased, with decreases of 14.9% (SD, 12.7%), 21.7% (17.9%), 27.1% (13.2%), 44.2% (9.7%), 47.9% (8.1%), and 61.2% (14.1%) at doses of 0.2, 0.5, 1.0, 1.7, 4.0, and 12.0 ug/kg-1, respectively. The four lowest doses induced limited and transient changes in heart rate, mean arterial pressure, and CI. Further investigation into potential perioperative uses of MED CRI is warranted.