The cardiopulmonary effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in dogs sedated with a combination of medetomidine and butorphanol.

OBJECTIVE: To compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467. STUDY DESIGN: Prospective, randomized experimental cross-over. ANIMALS: Eight purpose-bred beagles (two females, six males), 3-4 years old and weighing 14.5 ±1.6 kg (mean ± SD). METHODS: All dogs received four different treatments as follows: medetomidine 20 µg kg(-1) and butorphanol tartrate 0.1 mg kg(-1) IV and IM (MB), and MB combined with MK-467,500 µg kg(-1) (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (fR ), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO2 I) were calculated. After the follow-up period atipamezole 50 µg kg(-1) IM was given to reverse sedation. RESULTS: HR, CI and DO2 I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in fR between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.

Evaluation of renal impairment in dogs after envenomation by the common European adder (Vipera berus berus).

Envenomation by the common European adder (Vipera berus berus) causes clinical renal injury in dogs. In this study, serum concentrations of albumin, creatinine, total protein and urea were measured in 32 dogs bitten by adders. Urinary creatinine, protein, and retinol binding protein 4 concentrations, and the activities of γ-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), were measured in 32 affected dogs and 23 healthy controls. Clinical assessment was conducted with a grading scale and a renal function score was applied to classify dogs based on laboratory findings. Urinary protein:creatinine, GGT:creatinine and ALP:creatinine ratios appear to be useful in evaluating renal impairment in dogs with adder envenomation. Increasing kidney function score was correlated with increased urinary ALP:creatinine and GGT:creatinine ratios.

Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine.

OBJECTIVE: To evaluate the dexmedetomidine-induced reduction in organ blood flow with quantitative contrast-enhanced ultrasound (CEUS) method and to observe the influence of MK-467 on such reduction. STUDY DESIGN: Randomized cross-over study. ANIMALS: Six adult purpose-bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg). METHODS: Contrast-enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 µg kg(-1) (DEX) and DEX + MK-467 500 µg kg(-1) (DMK) intravenously (IV). The kidney (10-15 minutes post-treatment), spleen (25-30 minutes post-treatment), small intestine (40-45 minutes post-treatment) and liver (50-55 minutes post-treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash-in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination. RESULTS: AT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration. CONCLUSIONS: Contrast-enhanced ultrasound was effective in detecting DEX-induced changes in blood flow. MK-467 attenuated these changes. CLINICAL RELEVANCE: Clinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK-467 might beneficially impact the haemodynamic function of sedation with alpha-2 adrenoceptor agonists.

Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

OBJECTIVE: To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. STUDY DESIGN: Experimental randomized blinded crossover study. ANIMALS: Six healthy horses. METHODS: Detomidine (10 µg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 µg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p < 0.05. RESULTS: A significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.

Thermographic imaging of superficial temperature in dogs sedated with medetomidine and butorphanol with and without MK-467 (L-659'066).

OBJECTIVE: To record, with a thermal camera, peripheral temperature changes during different sedation protocols and to relate the results to changes in the rectal temperature. STUDY DESIGN: Randomized crossover part-blinded experimental study. ANIMALS: Eight healthy purpose-bred neutered Beagles (two females and six males) weight 14.5 ± 1.6 kg (mean ± SD) and aged 3-4 years. METHODS: Each dog was sedated four times. Treatments were medetomidine 20 µg kg(-1) and butorphanol 0.1 mg kg(-1) (MB) with or without MK-467 500 µg kg(-1) (MK). Both drug combinations were administered IV and IM as separate treatments. A thermal camera (T425, FLIR) with a resolution of 320 by 240 was used for imaging. The dogs were placed in lateral recumbency on an insulated mattress. Digital (DFT) and metatarsal footpad temperatures (MFT) were measured with thermography. Thermograms and rectal temperature (RT) were taken before and at 3, 10, 20, 30, 45 and 60 minutes after treatment. RESULTS: At 60 minutes after drug administration, MFT was higher (p < 0.001) after MB+MK (34.5 ± 1.1 IV, 34.8 ± 0.5 IM) than MB (31.1 ± 2.9 IV, 30.5 ± 3.6 IM), DFT was higher (p < 0.001) after MB+MK (33.6 ± 1.4 IV, 34.0 ± 0.6 IM) than MB (26.7 ± 1.4 IV, 26.7 ± 2.5 IM), and RT was lower (p < 0.001) after MB+MK (36.7 ± 0.8 IV, 36.9 ± 0.3 IM) than MB (37.5 ± 0.3 IV, 37.4 ± 0.4 IM), with both routes. The change from baseline was greater with MB+MK than MB in all variables. CONCLUSIONS: Superficial temperature changes can be seen and detected with thermography. MK-467 used with MB resulted in increased superficial temperatures and a decline in rectal temperature compared to MB alone. CLINICAL RELEVANCE: The sedation protocol may influence core temperature loss, and may also have an effect on thermographic images.

A comparison of thermographic imaging, physical examination and modified questionnaire as an instrument to assess painful conditions in cats.

Pain recognition in cats is difficult and requires a multidisciplinary approach for diagnosis. A total of 103 client-owned cats were enrolled in this prospective, blinded clinical trial. Cats were invited to the clinic, or presented for annual rechecks/vaccinations, or gastrointestinal, dental or locomotor problems. The cats were of different breeds; both shorthaired and longhaired cats were included. Those cats that tolerated it were palpated and all cats were examined with the non-invasive method of thermographic imaging. Owners filled out a questionnaire about their cat's behaviour and estimated whether the cat was in any pain. The agreement between a questionnaire and thermographic imaging or palpation was low. Also, the agreement between the owner's estimation of pain and thermographic imaging or palpation was low. The agreement between palpation and thermographic imaging was moderate, suggesting that thermographic imaging is a potential tool in clinical practice for detecting and screening cats that are, potentially, in pain.

Thermographic imaging of the superficial temperature in racing greyhounds before and after the race.

A total of 47 racing greyhounds were enrolled in this study on two race days (in July and September, resp.) at a racetrack. Twelve of the dogs participated in the study on both days. Thermographic images were taken before and after each race. From the images, superficial temperature points of selected sites (tendo calcaneus, musculus gastrocnemius, musculus gracilis, and musculus biceps femoris portio caudalis) were taken and used to investigate the differences in superficial temperatures before and after the race. The thermographic images were compared between the right and left legs of a dog, between the raced distances, and between the two race days. The theoretical heat capacity of a racing greyhound was calculated. With regard to all distances raced, the superficial temperatures measured from the musculus gastrocnemius were significantly higher after the race than at baseline. No significant differences were found between the left and right legs of a dog after completing any of the distances. Significant difference was found between the two race days. The heat loss mechanisms of racing greyhounds during the race through forced conduction, radiation, evaporation, and panting can be considered adequate when observing the calculated heat capacity of the dogs.

Proteomic profiling of dog urine after European adder (Vipera berus berus) envenomation by two-dimensional difference gel electrophoresis.

Between April and September every year, many dogs in Finland are bitten by Vipera berus berus, also known as the European adder, the only venomous snake in the area. Exposure to snake bite venom causes local and systemic symptoms and in severe cases can lead to death. Urine samples were collected from four dogs bitten by V. berus berus and treated in the intensive care unit of the Veterinary Teaching Hospital at the University of Helsinki. The inclusion criteria were a strong suspicion of an adder bite no more than two days before admission and clinical signs of an adder bite. Exclusion criteria were defined as ongoing treatment with glucocorticoids or a known history of liver or kidney diseases. Six privately owned, healthy dogs were obtained as controls. Samples were subjected to 2D-DIGE analysis. Image analysis was performed with DeCyder 7.0 2D software, and protein spots demonstrating a minimum 1.5-fold difference in average spot volume ratios between envenomed and control dogs with a Student's t-test p-value of less than 0.05 were picked and identified using LC-MS/MS. In 2D-DIGE analysis, seven proteins were significantly (p < 0.05) over-expressed in the urine of dogs bitten by V. berus berus compared to the control group. From these, five proteins were identified: beta-2-microglobulin (b2MG), alpha-1-antitrypsin (AAT), albumin, fetuin-B and superoxide dismutase (SOD1). Results indicate that envenomation by V. berus berus alter the urinary protein profile in dogs.

Comparison of three thermal cameras with canine hip area thermographic images.

The objective of this study was to compare the method of thermography by using three different resolution thermal cameras and basic software for thermographic images, separating the two persons taking the thermographic images (thermographers) from the three persons interpreting the thermographic images (interpreters). This was accomplished by studying the repeatability between thermographers and interpreters. Forty-nine client-owned dogs of 26 breeds were enrolled in the study. The thermal cameras used were of different resolutions-80 × 80, 180 × 180 and 320 × 240 pixels. Two trained thermographers took thermographic images of the hip area in all dogs using all three cameras. A total of six thermographic images per dog were taken. The thermographic images were analyzed using appropriate computer software, FLIR QuickReport 2.1. Three trained interpreters independently evaluated the mean temperatures of hip joint areas of the six thermographic images for each dog. The repeatability between thermographers was >0.975 with the two higher-resolution cameras and 0.927 with the lowest resolution camera. The repeatability between interpreters was >0.97 with each camera. Thus, the between-interpreter variation was small. The repeatability between thermographers and interpreters was considered high enough to encourage further studies with thermographic imaging in dogs.