Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: A mutation in the glycogen synthase gene (GYS1) responsible for type 1 polysaccharide storage myopathy was recently identified in Quarter Horses and North American draught horses. The purpose of the present studies was to determine which North American and continental European horse breeds harbour the GYS1 mutation and to determine the severity of PSSM when horses carry both the GYS1 mutation and the RYR1 mutation responsible for malignant hyperthermia. When specifically targeting continental European draught horses the GYS1 mutation (H allele) was found to be present in 46% (185/403) of draught horses located in Belgium, France, Germany, The Netherlands, Spain and Sweden. Horses with the mutation were found in all 13 European draught horse breeds examined. In those breeds in which more than 15 animals were available for testing the highest percentage of GYS1 positive horses were found in the Belgian Trekpaard (92%; 35/38), Comtois (80%; 70/88), Netherlands Trekpaard (74%; 17/23), Rheinisch-Deutsches kaltblut (68%; 30/44) and the Breton (64%; 32/51). A second study was performed to determine the frequency of the GYS1 mutation and prevalence of genetic susceptibility to Type 1 PSSM in selected breeds from Europe and North America. The GYS1 mutation was detected in 11 breeds, including, in order of increasing allele frequency, Shires, Morgans, Appaloosas, Quarter Horses, Paints, Exmoor Ponies, Saxon-Thuringian Coldbloods, South German Coldbloods, Belgians, Rhenish German Coldbloods, and Percherons. The prevalence of genetic susceptibility to Type 1 PSSM in these breeds varied from 0.5% to 62.4%. The GYS1 mutation was not found in the sampled Thoroughbreds, Akhal-Tekes, Connemaras, Clydesdales, Norwegian Fjords, Welsh Ponies, Icelandics, Schleswig Coldbloods or Hanoverians, but failure to detect the mutation does not guarantee its absence. Lastly, a study was to performed to identify a modifying gene(s) for the severe clinical phenotype in a family with PSSM. A genetic association analysis was used to identify RYR1 as a candidate modifying gene. A rare, known equine RYR1 mutation, associated with malignant hyperthermia (MH), was found to segregate in this GYS1 PSSM family. Retrospective analysis of patient records (n=179) demonstrated that horses with both the GYS1 and RYR1 mutations had a more severe clinical phenotype than horses with the GYS1 mutation alone. A treadmill trial (n=8) showed that serum creatine kinase activity was higher and exercise intolerance greater in horses with both mutations compared to the GYS1 mutation alone. PARTICIPANTS: Stephanie Valberg, University of Minnesota. James Mickelson, University of Minnesota. Molly McCue, University of Minnesota. Danika Bannasch, University of California-Davis. Richard Piercy, Animal Health Trust, UK. Gerard Guerin, INRA, France John Baird, University of Guelph, Canada TARGET AUDIENCES: Target audiences are veterinarians, horse owners, horse breeders, and horse breed associations. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
This knowledge will help breed associations determine if they should screen for the GYS1 mutation and will alert veterinarians to a possible differential diagnosis for muscle pain, rhabdomyolysis or gait abnormalities. The fact that horses with PSSM are found without the GYS1 mutation indicates that a second form of PSSM exists. And, even though the RYR1 mutation occurs at a very low frequency in the general horse population, this study shows that when it occurs in conjunction with the dominantly inherited and much more common GYS1 mutation, it can result in a more severe PSSM phenotype. Genotyping is recommended in cases of exertional rhabdomyolysis, prior to or in combination with, muscle biopsy. However a significant proportion of horses with histopathological evidence of PSSM and/or exertional rhabdomyolysis have different diseases.
Publications
- McCue ME, Valberg SJ, Luccio M and Mickelson JR. (2008). Glycogen synthase 1 mutation in diverse breeds with polysaccharide storage myopathy. J Vet Intern Med 22, 1228-1233.
- Herszberg B, McCue ME, Larcher T, Mata X, Vaiman A, Chaffaux S, Cherel Y, Valberg SJ, Mickelson JR, Guerin G. (2008). A GYS1 gene is highly associated with polysaccharide storage myopathy in Cob Normand draft horses. Animal Genetics 40, 94-96.
- Tryon RC, Penedo MCT, McCue, ME PhD, Valberg SJ, Mickelson JR, Famula TR, Wagner ML, Jackson M, Hamilton M, Noteboon S, Bannasch DL. (2009). Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses. J Am Vet Med Assoc 234, 120-125.
- McCue ME, Valberg SJ, Jackson M, Lucio M and Mickelson JR. (2009). Polysaccharide Storage Myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation. Neuromuscular Disorders 19, 37-43.
- Stanley RL, Valberg SJ, McCue ME, Mickelson JR, McGowan C, Hahn C, Patterson-Kane J and Piercy RJ. (2009). A glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and exertional rhabdomyolysis occurs in a variety of UK breeds. Equine Veterinary Journal 41, 597-601.
- McCue ME, Armien AG, Lucio M, Mickelson JR, and Valberg SJ, (2009). Comparative skeletal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses. Vet Pathology 46, 1281-1291
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Progress 01/01/06 to 12/31/06
Outputs
Glycogen Branching Enzyme Deficiency (GBED). We hypothesized that the GBE1 mutation is present at a significant frequency and is responsible for a high percentage of late-term abortions and neonatal foal deaths in Quarter Horses. Our specific aims were: 1), to determine the normal and mutant GBE1 allele frequencies in American Quarter Horse and Paint Horse populations; and 2), to determine the frequency of homozygotes for the mutant GBE1 allele in specimens of aborted and neonatal foals obtained from major veterinary diagnostic laboratories. GBE1 allele frequencies. Samples were obtained from archived hair root samples submitted to the Veterinary Genetics Laboratory, UC-Davis for the purposes of parentage verification and breed registration requirements. No homozygous mutant horses were identified. The carrier frequencies were 8.3% for Quarter Horses, 7.1% for Paints, and 0.0 % for Thoroughbreds. GBE1 genotypes in dead and aborted foal populations. We obtained 332
tissue samples in paraffin blocks or hair root samples, derived from aborted or neonatal foals of known or suspected Quarter Horse ancestry from the TVMDL and CAHFS. We found that 8.7% were heterozygous and 9/332 cases (2.7%) were homozygous for the mutant GBE1 allele; eight of these were from late term abortions. Heart and/or skeletal muscle were stained with H&E and PAS and all but one case showed basophilic inclusion bodies and globular deposits of abnormal polysaccharide. Pedigree analysis. The stallion King P-234 was present at least once (average approximately five times), on both the sire and dam's side of all but two homozygous mutant GBED foals. The dam of the two affected foals that did not trace back to King P-234, but instead traced back to his sire Zantanon, through a half-brother San Siemon. Zantanon was present in all the heterozygous pedigrees. Both Zantanon and King P-234 were also present at least once (average approximately three times) in 26 of 29 randomly selected
homozygous normal Quarter Horses. Thus, pedigree analysis alone will not enable the prediction of GBED carrier status. Conclusions. GBED is a lethal recessive trait and similar carrier frequencies in living and post-mortem Quarter and Paint Horse populations indicate that the heterozygous genotype is unlikely to be deleterious. Veterinarians and breeders need to recognize that GBED may present not just as foals born alive which subsequently succumb to GBED, but perhaps more frequently as abortion. PCR analysis for the GBE1 mutation appears to be the most accurate addition to postmortem diagnostic tests currently used to evaluate aborted feti and neonatal foals for GBED. With 150,000 new Quarter Horse and 50,000 new Paint Horse registrations annually, and an approximate heterozygote frequency of 8%, we can project that 16,000 new heterozygous horses will be registered annually. GBE1 genotyping will allow breeders to make informed matings, while continuing to perpetuate popular Quarter
Horse bloodlines.
Impacts
This study determined that 10% of Quarter Horse related breeds are carriers of an autosomal recessive genetic mutation that causes abortion and fetal death. Further, at least 3% of abortions and still births in these breeds are due to foals being homozygous for the mutation.
Publications
- Wagner ML, Valberg SJ, Ames EG, Bauer MM, Wiseman JA, Penedo CT, Kinde H, Abbitt B, and Mickelson JR. Allele Frequency and Likely Impact of the Glycogen Branching Enzyme Deficiency Gene in Quarter Horse and Paint Horse Populations. J Vet Int Med 2006; Sep-Oct;20(5):1207-11
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Progress 01/01/05 to 12/31/05
Outputs
The multiyear UMN RER breeding trial, with diagnoses on 23 foals from at least one RER parent determined with an in vitro muscle contracture test, indicated that the inheritance pattern is consistent with autosomal dominant. We considered several genes of skeletal muscle sarcoplasmic calcium regulation, some of which cause heritable muscle contractility disorders in other species, to be candidate genes for RER. However, linkage analysis with microsatellite DNA markers flanking the chromosomal loci of the RYR1, CACNA1S, and ATP2A1 genes exluded these genes from causing RER. 398 microsatellite markers have been run on the 96 horse resource population. No markers had a LOD score greater than 3.0 required for proof of linkage, and only several had LOD scores greater than 1.0. Positions on ECA3, 13, 14, and 28, where two or more markers gave positive LOD scores are being followed up with additional markers that lie in the regions to confirm or exclude these potential loci.
243 of the 398 markers tested have excluded linkage at lod greater than -2.0 at a recombination fraction of 0.01. We are working to precisely define the areas around each marker that are excluded as well as find new markers for regions that can still contain the RER gene. We now estimate that approximately 75 percent of the equine genome is excluded from containing the RER gene, but a large fraction of the genome remains to be interrogated with informative markers.
Impacts
Identification of DNA markers closely linked to the RER gene would ultimately allow more accurate diagnosis of the disease, identification of susceptible horses, prediction of candidate disease-causing genes, and precise definition of the genetic alteration.
Publications
- No publications reported this period
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Progress 01/01/04 to 12/31/04
Outputs
Markers closely linked to the equine GBE1 gene were identified to assist us in the molecular genetic definition of GBE1 deficiency. A clone from the INRA equine BAC library, containing a segment of the GBE1 gene, was mapped to equine chromosome 26 (ECA26q12-q13) by FISH. This position was initially unexpected, in that the human GBE1 gene is located on HSA3p12, and no previous work had established synteny between HSA3p and ECA26. We then sought to verify this map location and determine the approximate length of the conserved chromosomal segment. A polymorphic microsatellite was identified in the original GBE1 BAC clone and genetically mapped to a known linkage group on ECA26 with the Animal Health Trust three-generation full-sibling equine reference family. In addition, partial equine sequences were obtained for selected genes on HSA3p, and PCR primers designed for typing on the Texas A & M University 5000 rad equine x hamster radiation hybrid panel. Five genes, ROBO2,
ROBO1, GBE1, POU1F1, and HTR1F, located in this order along a 10 Mb segment of HSA3p11-12, formed a strong RH linkage group. However, the GLB1, MITF, RYBP, and PROS1 genes, that flank this 10 Mb interval, were not contained in the GBE1 RH linkage group, and instead mapped to ECA16 or 19. All affected foals were homozygous for an allele of GBEms1 and UMNe56 while control foals showed allelic variation. The results confirmed an association between the disease GBED and the GBE1 gene. We then derived 90% of the sequence of GBE1cDNA using RT-PCR. MRNA was isolated from skeletal muscle or liver tissue and PCR primers initially derived from the human GBE1 sequence were used to amplify the GBE1 cDNA. The derived equine sequence was used to generate primers to amplify the majority of the cDNA sequence. PCR products were sequenced on an Applied Biosystems 3100 automated DNA sequencer. The partial cDNA sequence of GBE1 was used to design horse specific primers fro exon 2 and 15. These primers
were used to screen the CHORI-241 Equine BAC library, which was converted to PCR-able superpools at Texas A&M University. Clones containing the 5' and 3' ends of the GBE1 gene were isolated and sequenced directly. These techniques allowed us to derive the entire sequence of the GBE1 gene. The complete sequence of GBE1 gene was compared between control horses and affected foals. A C to A substitution in exon 1 at nucleotide 102 was identified in GBED foal cDNA changed codon 34 from a tyrosine (Y) to a premature stop codon (X). All 11 affected foals were homozygous for the mutation. The available samples from 11 sires or dams were heterozygous and all controls animals were homozygous.
Impacts
The University of Minnesota has a patent pending for a simple DNA based test utilizing hair samples from affected foals or potential breeding animals. Now owners are able to test their horses to see if they carry this gene and prevent this disease from occurring in Quarter horses and Paint horses through selective mating.
Publications
- Ward TL, Valberg SJ, Lear T, Guerin G, Milenkovic D, Swinburne J, Binns MM, Raudsepp T, Skow L, Chowdhary BP, and Mickelson JR. 2003 Genetic mapping of GBE1 and its association with glycogen storage disease IV in American Quarter Horses. Cytogenet Genome Res;102:201-206.
- Ward TL, Valberg SJ, Adelson DL, Abby CA3, and James R Mickelson JR. 2004 Glycogen Branching Enzyme (GBE1) Mutation Causing Fatal Glycogen Storage Disease IV in American Quarter Horse Foals Mammalian Genome;15:570-577.
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Progress 01/01/03 to 12/31/03
Outputs
A reduction in grain intake and addition of sodium bicarbonate to the diet are common recommendations for recurrent exertional rhabdomyolysis (RER). Recently high dietary fat has been advocated for RER to increase caloric intake without additional starch. The purpose of this study was to assess the effects of three isocaloric diets (28 MCal/day) on post-exercise serum CK activity in RER horses. Horse consumed a similar amount of hay and one of 3 supplements; HS was high in starch (21 percent), low in fat (3 percent) with a dietary cation anion balance (DCAB) of plus190; HB was the same but had 4.2 percent sodium bicarbonate with a DCAB of plus380, and HF was low in starch (9 percent) and high in fat (13 percent) with a DCAB of plus200. Five fit RER horses with a history of high serum CK, and abnormal skeletal muscle caffeine contracture tests were fed each diet for a three-week period. Horses were exercised with intervals of walk, trot, canter for 30 min five days a
week while consuming each diet. Blood samples were taken daily for analysis of pre- and post-exercise serum pH, (Na+), (K+), (HCO3-), ionized (iCa++) and post exercise CK. On the last day of each diet a urine sample was obtained from all horses to calculate urinary fractional excretion (FE) of Ca++, P, Mg++, Na+, K+ and Cl-, and a near maximal standardized exercise test (SET) was performed, during which serial measurement of blood (lactate) was performed. Results were analyzed using Analysis of Variance (significance P greater than 0.05). Post-exercise serum CK activity was above normal limits on HS and HB (2451 U/L +/- 681 and 2554 U/L +/- 1595) and was significantly lower on HF compared to the other two diets (407 U/L +/- 53). Pre- and post-exercise serum pH, [HCO3-] and [lactate] did not differ significantly between the diets. Post-exercise [iCa++] was significantly greater on HF. Urinary FE did not differ significantly between the diets. The results indicate a high fat/ low starch
diet significantly reduces post-exercise CK in RER horses undergoing treadmill exercise. Dietary bicarbonate supplementation appears to have no effect on the occurrence of rhabdomyolysis in RER horses.
Impacts
The results indicate a high fat/ low starch diet significantly reduces post-exercise CK in RER horses undergoing treadmill exercise. Dietary bicarbonate supplementation appears to have no effect on the occurrence of rhabdomyolysis in RER horses.
Publications
- McKenzie EC, Valberg SJ. Pagan JD, Carlson GP, MacLeay JM and DeLaCorte FD. 2002 Electrolyte balance in Thoroughbred horses with recurrent exertional rhabdomyolysis consuming diets with varying Dietary Cation-Anion Balance. Am J Vet Res 63:1053-1060. McKenzie EC, Valberg SJ, and Pagan JD. 2002 A review of dietary fat supplementation in horses with exertional rhabdomyolysis. Proceedings Am Assoc Equine Pract pp381-386. McKenzie EC, Valberg SJ, Godden S, Pagan JD, MacLeay JM, Geor RJ, Carlson GP. 2003 Effect of dietary starch, fat and bicarbonate content on exercise responses and serum creatine kinase activity in equine recurrent exertional rhabdomyolysis J Vet Int Med 17:693-701
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Progress 01/01/02 to 12/31/02
Outputs
Polysaccharide storage myopathy(PSSM) is a frustrating cause of chronic tying-up in Quarter Horses. PSSM is characterized by the accumulation of glycogen and an abnormal polysaccharide in muscle fibers. Glycogen accumulation in PSSM horses is not due to the inability of skeletal muscle to burn glycogen as fuel. Rather, it now appears that excessive glycogen storage in PSSM horses is due to enhanced insulin sensitivity of skeletal muscle. In effect, PSSM appears to be a common developmental disorder in glucose/glycogen homeostasis that naively could be classified as the opposite of type 2 diabetes. Since its identification, PSSM has been widely discussed on Internet sites with controversy arising over the amount and type of fat most suitable for these horses. Currently, veterinarians vary in the recommended amount of dietary fat from 3 to 25% of the total daily diet. Specifically, our objectives were; 1.To determine if a defect in the trafficking of the protein
responsible for transport of glucose into muscle (glucose transporters (GLUT4))is abnormal in horses with PSSM. Results to date suggest that PSSM horses compared to normal horses have a similar total amount of the insulin sensitive GLUT4 and 2 fold fewer GLUT1 transporters. The individual muscle fibers with abnormal polysaccharide have increased GLUT4 content. Of great interest was the finding that PSSM muscle has an almost 1.5 fold higher quantity of insulin receptors in muscle compared to normal horses. A simple insulin sensitivity test was developed in light of these findings and we found that foals out of a dam or sire with PSSM showed a much more dramatic drop in blood glucose compared to control foals when given an IV insulin injection. We are continuing these investigations in year 2. 2.To determine the effect of variable amounts of fat supplement on glucose and insulin responses to feeding, muscle glycogen concentrations and serum CK activity with exercise. Results to date
suggest that the most important factor for PSSM horses is the amount of starch rather than the amount of fat in the diet. Furthermore, there appears to be individual variation in the clinical severity of exertional rhabdomyolysis in PSSM horses that correlates to the amount of starch tolerated without elevations in serum CK activity. 3.To determine the perceived clinical response of PSSM horses to dietary and training management in the field.Results showed that over 90% of Quarter horses with PSSM improved if owners removed grain, fed grass hay and provided a fat supplement to horse that were exercised regularly and turned out. Feeding a fat supplement alone without regular exercise did not result in the same degree of improvement. Compliance with the recommendations improved dramatically after 2000 as owners and veterinarians became more aware of the disease. In conclusion,PSSM is associated with an increased expression of insulin receptors in skeletal muscle,and enhanced insulin
sensitivity. By reducing the dietary starch content, adding fat and increasing daily exercise, daily blood glucose and insulin concentrations can be reduced and fewer clinical signs of muscle stiffness are experienced by PSSM horses.
Impacts
(N/A)
Publications
- No publications reported this period
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Progress 01/01/01 to 12/31/01
Outputs
Seven related Quarter Horse foals that died by 7 weeks of age were examined for glycogen branching enzyme deficiency. Clinical signs varied from stillbirth, transient flexural limb deformities, seizures and respiratory or cardiac failure to persistent recumbency. Leukopenia (5/5 foals) as well as high serum CK (5/5), AST (4/4), and GGT (5/5) activities were present in most foals, and intermittent hypoglycemia was present in 2 foals. Gross postmortem lesions were minor except for pulmonary edema in 2 foals. Muscle, heart or liver samples from the foals contained abnormal PAS-positive globular or crystalline intracellular inclusions in amounts proportional to the foal's age at death. Accumulation of an unbranched polysaccharide in tissues was suggested by a shift in the iodine absorption spectra of polysaccharide isolated from liver and muscle of affected foals. Skeletal muscle total polysaccharide concentrations were reduced by 30 %, but liver and cardiac muscle
glycogen concentrations were normal. Activities of several glycolytic enzymes were normal, whereas glycogen branching enzyme activity (GBE) was virtually absent in cardiac and skeletal muscle, as well as in liver and peripheral blood cells of affected foals. GBE activity in peripheral blood cells of dams of affected foals and several of their half-siblings or full siblings were 50% of controls. GBE protein in liver determined by Western blot was markedly reduced to absent in affected foals, and in a half-sibling of an affected foal was approximately half the amount of normal controls. Pedigree analysis also supported an autosomal recessive mode of inheritance. The affected foals have at least 2,600 half-siblings. Consequently, GBE deficiency may be a common cause of neonatal mortality in Quarter Horses that is obscured by the variety of clinical signs that resemble other equine neonatal diseases.
Impacts
(N/A)
Publications
- Byrne E, Jones SL, Valberg SJ, Zimmel DN and Cohen N. 2000. Rhabdomyolysis in two foals with polysaccharide storage myopathy and concurrent pneumonia. Comp Cont Educ, 22:503-507.
- Valberg SJ, Mickelson JR, Ward TL, Rush B, Kinde H, Hiraragi H, Nahey D, and Fyfe J. 2001. Glycogen branching enzyme activity in Quarter Horse foals. J Vet Intern Med, 15:572-580.
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Progress 01/01/00 to 12/31/00
Outputs
Exertional rhabdomyolysis in a population of related Quarter Horses is caused by a defect that results in excessive glycogen storage and the accumulation of an abnormal polysaccharide in skeletal muscle. The excessive glycogen storage in this polysaccharide storage myopathy (PSSM) is not due to the inability to metabolize glycogen. Previous studies of the effects of a single intravenous bolus of insulin or glucose suggest that horses with PSSM have enhanced glucose clearance due to uptake into skeletal muscle. The purpose of this study was to determine whole body glucose clearance in PSSM horses during a steady state of hyperinsulinemia, using clamping techniques adapted from human diabetic studies. Four healthy control horses ranging in age from 2-11 yrs and 5 PSSM horses ranging in age from 3-14 yrs were used in this study. Horses were fed hay and stall rested for 1 month followed by a 12 hr fast immediately prior to the study. A right jugular venous catheter was
used to collect blood every 5 min for determination of glucose (QID glucometer) and insulin concentrations (RIA). A left jugular catheter was used for controlled glucose and insulin infusion. Insulin was diluted in isotonic saline and homologous blood and infused at 3 mU/min/kg body weight to maintain concentrations at a plateau of 150-300 mU/ml. Blood glucose was monitored every 5 min to determine the rate of glucose infusion necessary in order to maintain blood glucose at approximately 100 mg/dl (range 95 to 110 mg/dl). The rate of infusion during steady state 30 min time blocks was significantly higher for PSSM horses than controls (p less than 0.001). These results confirm our hypothesis that greater insulin sensitivity in horses with PSSM results in enhanced blood glucose clearance . We suggest that high muscle glycogen concentrations in PSSM horses are due to enhanced clearance of blood glucose into skeletal muscle, the largest mass of insulin-sensitive tissue in the body.
Impacts
(N/A)
Publications
- No publications reported this period
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Progress 01/01/99 to 12/31/99
Outputs
Electrolyte Concentrations with varying Dietary Cation-Anion Balance (DCAB) in Thoroughbred horses with recurrent exertional rhabdomyolysis (RER) A form of RER in Thoroughbreds (TBs) is due to an inherited abnormality in intracellular calcium regulation. Dietary induced variations in serum electrolyte concentrations and acid base status may alter the expression of RER. The purpose of this study was to assess the effects of three diets of varying DCAB, on electrolyte and mineral balance in TBs. Five control and six RER mares were used. RER was diagnosed based on history, serum CK, and abnormal responses to caffeine contracture testing. Three diets with varying DCAB were each fed for a two-week period. An anionic diet (low DCAB +87) was fed initially, followed by a medium DCAB diet (+187) and then a cationic diet (High DCAB +400). Blood samples were taken daily from all horses for analysis of Na+, K+, P, Cl-, HCO3-, total Ca++ and ionized Ca++ concentrations. For the
last three days of each diet total urine and fecal mineral and electrolyte content was measured. Results were analyzed using Analysis of Variance (significance P less than 0.05). No differences in measured parameters were found between RER and control horses. Serum pH, [Na+], [Cl,, [K+], [HCO3-] and ionized [Ca++] differed significantly between the diets. Daily balance of Ca++, P, Mg++, Na++, K+ and Cl- was calculated from dietary, urine and fecal concentrations. A negative daily balance of Ca++, P, Mg ++ and Na+ was observed on the medium and high DCAB diets. Total daily balance of Ca++, Na+, and K+ did not differ significantly between diets. The daily balance of all parameters did not differ significantly between medium and high DCAB diets. Daily balance of all substances was higher on the low DCAD diet, but was significantly higher than the medium or high DCAB diets for P, Mg++, and Cl-. The results suggest diets with varying DCAB levels can produce significant effects on
electrolyte and mineral metabolism in horses. Subsequent studies will focus on the effect of dietary cation anion balance (DCAB) on serum creatine kinase activities in RER horses undergoing treadmill exercise.
Impacts
(N/A)
Publications
- No publications reported this period
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Progress 01/01/98 to 12/31/98
Outputs
Polysaccharide storage myopathy (PSSM) was studied in Quarter horses. All 13 glycogenolytic/glycolytic enzymes were normal in PSSM. Increased glycogen storage is therefore not likely due to a glycogenolytic/glycolytic defect. PSSM horses utilize 3x more glycogen and make 2x more lactate than normal Quarter horses during near-maximal exercise; therefore, glycogenolysis and glycolysis are functional in these horses. PSSM horses have 1.5x faster glucose excursion from the blood stream and enhanced insulin sensitivity. Exercise in PSSM horses is beneficial in part because it causes a relative insulin resistance. Foals from PSSMXPSSM matings have enhanced glucose clearance, glycogen storage and rhabdomyolysis by 6 months with abnormal polysaccharide accumulation by 2 years. A diet low in soluble carbohydrate and high in fat from rice bran combined with daily exercise dramatically reduces the number of episodes of rhabdomyolysis.
Impacts
(N/A)
Publications
- Valberg, S.J., Townsend, D., MacLeay, J.M. and Mickelson, J.R. 1998. Glycolytic capacity and phosphofructokinase regulation in horses with polysaccharide storage myopathy. Am.J.Vet.Res. 59:782-785.
- Valberg, S.J., MacLeay, J.M., Billstrom, J.A., Hower-Moritz, M.A. and Mickelson, J.R. 1999. Skeletal muscle metabolic response to exercise in horses with polysaccharide storage myopathy. Equine Vet.J. 31:43-47.
- De La Corte, F.D., Valberg, S.J., Troedsson, M.T., and Mickelson, J.R. 1998. Developmental onset of polysaccharide storage myopathy in Quarter Horse foals. Proceedings ACVIM.
- Valberg, S.J., MacLeay, J.M. and Mickelson, J.R. 1997. Polysaccharide storage myopathy associated with exertioanl rhabdomyolysis in horses. Comp.Cont.Edu. 19(9)10:1077-1086.
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Progress 01/01/91 to 12/30/91
Outputs
1. The origin of echinocytes as dehydrated red blood cells and not from the spleen was discovered and explained findings in racing horses. Pentoxifylline was found to increase blood viscosity, whereas Lasix was found to reduce echinocytes and dense red blood cells. 2. Gait analysis of horses with osteochondral fragments in carpal joints revealed significant decrease in rage of motion as well as a particular head nod. Administration of anti-inflamatory (non-steroidal) drugs returned gait to normal. 3. Gentamycin pharmacokinetics in 20 septicemic neonatal foals was evaluated. The animals did not reach recommended blood levels following the recommended dose (3.3 mg/kg), but could reach this level if an initial "loading" dose of 4.5 mg/kg was used. There was considerable variability in gentomycin blood levels between animals.
Impacts
(N/A)
Publications
- GEOR, R.J., BRASHIER, M.K. 1991. Gentamicin dosage in neonatal foals: A rational approach. American Association of Equine Practitioners Proceedings (in press).
- CLANTON, C., KOBLUK, C., ROBINSON, R.A. and GRODON, B. 1991. Monitoring surface conditions of a thoroughbred racetrack. JAVMA, Vol. 198, No. 4, pp. 613-620.
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Progress 01/01/90 to 12/30/90
Outputs
This study will evaluate the pathogenesis of several horse problems including infertility, osteochondral fragments (bone chips) in the carpal joints, foal septicemia and pulmonary hemorrhage. In the area of infertility, emphasis has been given to evaluating the presence of antisperm antibodies in infertile or subfertile mares. The effect of bone chips on athletic performance, as well as the effect of pain-relieving drugs, is being evaluated on a treadmill. The effect of gentamycin on foal septicemia is being researched with particular emphasis on tissue concentration of the drug and potential effects on kidney function. The effect of furosemide (Lasix) and pentoxifylline (Trental) on exercise-induced pulmonary hemorrhage is being studied using in vitro assays of the drug's effects on the morphology and elasticity of red blood cells.
Impacts
(N/A)
Publications
- NO PUBLICATIONS REPORTED THIS PERIOD.
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Progress 01/01/89 to 12/30/89
Outputs
Objectives of this study are to improve diagnosis and therapy of conditions thatinterfere with reproduction and to improve neonatal viability. To discover factors that impact on equine athletic performance and develop means of evaluating them, including metabolism of drugs that affect performance. The efficacy of the prostaglandin analog, alfaprostol, is being studied as an alternative to human chorionic gonadotropin for induction of ovulation in mares. The study includes assessment of the fertility of induced ovulations. Stallions and mares implicated in unexplained infertility are being examined to determine if they have significant anti-sperm antibodies, relative to control horses. In regard to viability of neonatal foals, the pharmacokinetics of the antibody gentamicin, including optimal dosage in septicemic foals, is being investigated. Recordings of gaits of horses exercised at a track and on a treadmill are being subjected to computer-assisted analysis.
Kinematic changes resulting from differences in hoof angle and differences associated exercise conditions are being investigated. Also, ultrasonograms of equine joints and flexor tendons are being made in normal and lame horses. Additional investigations include exercise-induced pulmonary hemorrhage and laboratory analysis of furosemide and opiate drugs.
Impacts
(N/A)
Publications
- NO PUBLICATIONS REPORTED THIS PERIOD.
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