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.     

Intervertebral disc disease in Dachshunds radiographically screened for intervertebral disc calcifications

Background

Intervertebral disc disease (IDD) is a very common neurological disease, Dachshunds being the breed most often affected. In this breed, IDD has a hereditary background and is associated with intervertebral disc calcification (IDC), an indicator of severe intervertebral disc degeneration. In Finland, spinal radiography is used, when screening for IDC before breeding Dachshunds. We evaluated the association between IDC and IDD in Finnish Dachshunds radiographically screened for IDC.A questionnaire was sent to owners of 193 radiographically screened Dachshunds aged at least ten years. Clinical signs indicative of IDD were compared with IDC grade (grade 0 = no calcifications, grade 1 = 1 – 2 calcifications, grade 2 = 3 – 4 calcifications and grade 3 = 5 or more calcifications) and with age at the time of the radiographic examination. The diagnosis of IDD was confirmed by a veterinarian.

Results

IDD was common in the study population with 31% of dogs being affected. IDD and IDC were clearly connected (P < 0.001); IDD was rare in dogs with no calcifications (grade 0) and common in dogs with severe IDC (grade 3). The IDC grade was strongly positively associated with frequency of back pain periods (P < 0.001), and dogs with IDC grade 3 had frequent periods of pain. Reluctance to jump onto a sofa had a strong positive association with back pain. No association existed between age of the dog at the time of the radiographic examination and clinical signs indicative of IDD.

Conclusions

Radiographically detected IDC and IDD are common in Finnish Dachshunds and are strongly associated with one another. Spinal radiography is an appropriate screening tool for breeders attempting to diminish IDC and IDD in Dachshunds. A breeding program that screens dogs and selects against IDC can be expected to reduce the occurrence of IDD in future. Twenty-four to 48 months of age is a suitable age for screening.

Electronic supplementary material

The online version of this article (doi:10.1186/s13028-014-0089-4) contains supplementary material, which is available to authorized users.     

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.     

Molecular markers and doubled haploids in European plant breeding programmes

The breeding companies and laboratories involved in this article cover a wide range of crops grown in the temperate climate zone: small grain cereals, oilseed crops, forage crops, turf, vegetables and potato. Speed and efficiency are becoming increasingly important in variety breeding and doubled haploids (DH) and genetic markers are important biotechnological tools to accelerate materials to market. Collaborative research between universities, research institutions and breeding companies has resulted in the routine use of DH technology and molecular markers in practical breeding of barley, wheat and rapeseed. DH populations have been established not only for barley, wheat and rapeseed, but for rye, oat and triticale, where DH technology is less developed. A driver here is the value of the crop e.g. although wheat is less responsive to DH production the value of the end product makes the effort worthwhile. Simple and rapid DNA extraction methods used in high-throughput marker assisted selection (MAS) systems are essential for routine use of markers. MAS is used both to monitor the presence of genes of interest and also to monitor the genetic background. DH technology in forage, turf and vegetables is still in progress and the practical use of markers in all crops is limited by access to trait linked markers. Collaboration and technology transfer with universities, research institutions and breeding companies is essential for the improvement of both DH protocols in recalcitrant crops and marker technology in all crops.     

Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral alpha2-antagonist MK-467 in dogs

Objective

We investigated the plasma concentrations and cardiovascular effects of intramuscularly (IM) administered medetomidine, administered alone or with three different doses of MK-467.

The impact of medetomidine on the protein‐binding characteristics of MK‐467 in canine plasma

This study determined the unbound fraction of the peripheral α₂‐adrenoceptor antagonist MK‐467 alone and combined with medetomidine. MK‐467 (0.1, 1 and 10 μm ) was incubated in canine plasma with and without medetomidine (molar ratio 20:1), with human serum albumin (HSA) and with α1‐acid glycoprotein (AGP). Rapid equilibrium dialysis was used for the measurement of protein binding. All samples were analysed by liquid chromatography and tandem mass spectrometry to obtain the unbound fraction (f_u) of MK‐467. Unbound fractions (f_u) of MK‐467 in canine plasma (mean ± standard deviation) were 27.6 ± 3.5%, 26.6 ± 0.9% and 42.4 ± 1.2% at 0.1, 1.0 and 10 μm concentrations, respectively. In the presence of medetomidine, f_u were 27.5 ± 0.4%, 26.6 ± 0.9% and 41.0 ± 2.4%. The f_u of MK‐467 in HSA were 50.1 ± 2.5% at 0.1 μm , 49.4 ± 1.2% at 1.0 μm and 56.7 ± 0.5% at 10 μm . f_u of MK‐467 in AGP was 56.3 ± 3.7% at 0.1 μm , 54.6 ± 5.6% at 1.0 μm and 65.3 ± 0.4% at 10 μm . Protein binding of MK‐467 was approximately 70% between 0.1 and 1.0 μm . Medetomidine had no apparent effect on the protein binding of MK‐467.     

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.     

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.

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.     

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.