MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy

Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val₄₃₂Ile and Lys₄₅₇Gln) and one in CD147 (Met₁₂₅Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found.     

MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy

Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val₄₃₂Ile and Lys₄₅₇Gln) and one in CD147 (Met₁₂₅Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found.     

Pharmacokinetics of intra‐articular morphine in horses with lipopolysaccharide‐induced synovitis

ObjectiveTo describe the pharmacokinetics of intra-articularly (IA) administered morphine.Study designExperimental randomized, cross-over study.AnimalsEight adult healthy mixed breed horses aged 6.5 ± 2.3 (mean ± SD) years and weighing 535 ± 86 kg.MethodsUnilateral radiocarpal synovitis was induced by IA injection of 3 μg lipopolysaccharide (LPS) on two occasions (right and left radiocarpal joint, respectively) separated by a 3-week wash-out period. Treatments were administered 4 hours post-LPS-injection: Treatment IA; preservative free morphine IA (0.05 mg kg^?1) plus saline intravenous (IV) and treatment IV; saline IA plus preservative free morphine IV (0.05 mg kg^?1). Concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide (M6G) were determined repeatedly in serum and synovial fluid (SF) by high-performance liquid chromatography mass spectrometry, at 2 and 4 hours and then at 4 hours intervals until 28 hours post-treatment.ResultsInjection of LPS elicited a marked and comparable synovitis in all LPS-injected radiocarpal joints. IA administered morphine was detectable in SF of all eight joints 24 hours post-treatment and in 6/8 joints 28 hours post-treatment. The terminal half-life of morphine in SF was estimated to be 2.6 hours. IA administration of morphine resulted in mean serum concentrations of morphine below 5 ng mL^?1 from 2 to 28 hours after treatment.Conclusions and clinical relevanceIntra-articularly administered morphine remained within the joint for at least 24 hours. At the same time only very low serum concentrations of morphine and M6G were detected. The present results suggest that IA morphine at 0.05 mg kg^?1 may be used for IA analgesia lasting at least 24 hours and give strong support to the theory that previously observed analgesic and anti-inflammatory effects of IA morphine in horses are most likely to be mediated peripherally.     

Intra‐abdominal hypertension in horses

Intra‐abdominal hypertension (IAH) may lead to a multiple organ dysfunction syndrome associated with significant dysfunction of the cardiovascular, respiratory, renal, gastrointestinal and central nervous systems of human patients. A recent prospective multicentre epidemiological investigation in man concluded that IAH was associated with an increased risk of mortality in critically ill patients. In this review, we present current information pertaining to the potential clinical importance of IAH in the context of equine clinical practice. In conclusion, consideration of intra‐abdominal pressure should be a part of the clinical assessment of patient well‐being in critically ill equine patients.     

Exercised-induced pulmonary hemorrhage in polo and racing horses

Philippine polo and racing horses were examined for exercise-induced pulmonary hemorrhage after their competitive exercise. Exercise-induced pulmonary hemorrhage occurred in 11.1% of the polo horses and 64% of the racing horses. None of the horses had blood at the nostrils.     

Quantitative analysis of short‐ and long‐distance racing performance in young and adult horses and association analysis with functional candidate genes in Spanish Trotter horses

The association of five candidate genes with sporting performance in young and adult Spanish Trotter horses (STHs) was performed according to a previous selection based on quantitative analysis of the trait time per kilometre (TPK). A total of 334 516 records of TPK from 5958 STHs were used to estimate the estimated breeding values (EBVs) at different age groups (young and adults horses) throughout the range of distances (1600–2700 m) using a bicharacter random regression model. The heritability estimated by distance ranged from 0.16 to 0.40, with a different range for the two age groups. Considering the animals with the best and the worst deregressed EBV, 321 STHs were selected for SNP genotyping in MSTN, COX4I2, PDK4, DMRT3 and CKM genes. An association analysis based on ridge and logistic regression revealed that the young trotters with genotype GG in PDK4 (p < 0.05) and AA of DMRT3 (p < 0.001) SNPs show the best potential in short‐distance races, while those carrying the genotype AA in DMRT3 (p < 0.001) and CC in CKM (p < 0.05) genes seem to be the best in long‐distance races. Adult trotters with genotype AA in DMRT3 also display greater speed (p < 0.05) and endurance (p < 0.001).     

Hyoscine‐N‐butylbromide premedication on cardiovascular variables of horses sedated with medetomidine

ObjectiveTo evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses.Study designRandomized, crossover experimental study.AnimalsEight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years.MethodsBaseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2^oAV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO₂) and oxygen (PaO₂) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg^?1; group HIV), IM hyoscine (0.3 mg kg^?1; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 μg kg^?1) was administered IV and measurements were recorded at various time points for 130 minutes.ResultsMedetomidine induced bradycardia, 2^oAV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2^oAV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute^?1 and 241 ± 37 mmHg versus 65 ± 16 beats minute^?1 and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO₂ and PaO₂ were not significantly changed by administration of medetomidine with or without hyoscine.Conclusion and clinical relevanceHyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.     

Life-threatening hemorrhage from enterotomies and anastomoses in 7 horses

OBJECTIVE: To report our experience with horses that presumptively had severe intraluminal hemorrhage from enterotomy or anastomosis. STUDY DESIGN: Clinical study. ANIMALS: Six adult horses and 1 adult donkey. METHODS: A retrospective study was conducted at the University of Illinois (April 1994 to December 2001) to determine the clinical course and outcome of horses with melena and/or anemia and evidence of life-threatening hemorrhage from intestinal incisions. Medical records of all horses that had colic surgery were reviewed to determine the proportion of horses with this complication. In addition, horses that fit the same criteria identified in 3 other veterinary clinics were included. RESULTS: Three horses (1.3%) of those that had enterotomy or anastomosis at the University of Illinois and 4 horses from other clinics had complications presumptively related to severe hemorrhage from these intestinal procedures. Melena became evident within 72 hours of surgery and lasted 12 to 96 hours. Six horses had an acute and severe drop in packed cell volume (PCV), increased heart rates, and other signs of acute hemorrhage, and 1 horse had signs of colic postoperatively. Horses were administered intravenous formalin (3 horses) and whole blood transfusions (4 horses). Repeat celiotomy was performed on 2 horses. In 1 of these horses, a bleeding artery was ligated in the edge of the original enterotomy, and, in the other, a 25-cm-diameter intraluminal blood clot was found occluding the pelvic flexure. A horse that had jejunocolostomy for cecal impaction was not treated for hemorrhagic shock but was euthanatized and necropsied. Necropsy revealed blood-filled bowel from the jejunocolostomy to the anus. One of the remaining 6 horses died of enterocolitis and 5 survived to discharge. CONCLUSIONS: Hemorrhage from incisional edges, particularly in the large intestine, should be considered a rare but possibly fatal complication of enterotomy or anastomosis in horses. CLINICAL RELEVANCE: To prevent fatal hemorrhage from incisional edges during enterotomy or anastomosis, large vessels should be ligated at the original surgery, and hemostatic effects of different closure techniques should be considered. No intraoperative or postoperative findings were useful to predict this complication, and response to supportive medical therapy was favorable.