Horses were domesticated from the Eurasian steppes 5,000–6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection.

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

Cats (n = 6) were administered dexmedetomidine (DEX) and medetomidine (MED) at three different dose levels in a randomized, blinded, cross-over study. DEX was administered at 25, 50 and 75 microg/kg (D25, D50 and D75), corresponding to MED 50, 100 and 150 microg/kg (M50, M100 and M150). Sedation, analgesia and muscular relaxation were scored subjectively. Heart and respiratory rates and rectal temperature were measured. Corresponding doses of DEX and MED were compared. Effects were also compared between dose levels for each compound. At dose level 2 (D50-M100), the duration of effective clinical sedation was significantly shorter after DEX (202.5 +/- 16.0 min) than after MED (230.0 +/- 41.2 min). Proceeding from D50-M100 to D75-M150, the duration of effective clinical sedation was increased more after DEX (by 57.5 +/- 38.4 min) than after MED (by 14.2 +/- 41.9 min) Increasing from D50-M100 to D75-M150, heart rate was further decreased after DEX (by 8.1 +/- 13.4%) but not after MED. There was no statistically significant difference between corresponding doses of DEX and MED for any of the other parameters studied. Changes in sedation, analgesia and muscular relaxation were dose-dependent. It was concluded that anaesthetic effects of medetomidine in cats are probably due entirely to its d-isomer and that dexmedetomidine at 25, 50 and 75 microg/kg induces dose-dependent sedation, analgesia and muscular relaxation of clinical significance in cats.

Chronic pain could be assessed in dogs with CHD through completion of the study questionnaire by a person familiar with the pet (eg, owner) after receiving appropriate education in its use. Eleven variables were identified as being potentially useful in assessment of chronic pain in dogs.

Dexmedetomidine is at least as safe and effective as medetomidine for use as a premedicant in dogs undergoing propofol-isoflurane anesthesia.

No abstract

Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs.