Objective—To determine pharmacokinetics and oral bioavailability of metformin in healthy horses.
Animals—4 adult horses.
Procedures—6 g of metformin was administered 3 times IV and PO (fed and unfed) to each horse, by use of a crossover design, with a 1-week washout period between treatments. Plasma metformin concentration was determined via high-pressure liquid chromatography.
Results—Mean ± SD distribution half-life of metformin following IV administration was 24.9 ± 0.4 minutes with a volume of distribution of 0.3 ± 0.1 L/kg. Mean area under the curve was 20.9 ± 2.0 h·μg/mL for IV administration; PO administration resulted in area under the curves of 1.6 ± 0.4 h·μg/mL in unfed horses and 0.8 ± 0.2 h·μg/mL in fed horses. Bioavailability was determined to be approximately 7.1 ± 1.5% in unfed horses and 3.9 ± 1.0% in fed horses. The maximal concentration following PO administration in unfed horses was 0.4 ± 0.1 μg/mL with a time at maximal concentration of 0.9 ± 0.1 hours. In fed horses, maximal concentration was reduced to 0.3 ± 0.04 μg/mL with a time at maximal concentration at 1.3 ± 0.3 hours.
Conclusions and Clinical Relevance—The low bioavailability of metformin may explain the reported lack of clinical success in improving insulin sensitivity with metformin treatment in horses. Dosages and dose intervals previously used may have been insufficient to achieve plasma concentrations of drug comparable to the therapeutic range achieved in humans. Therefore, a larger and more frequently administered dose may be required to fully evaluate efficacy of metformin in horses.
Objective—To characterize onset and clinical signs of
polysaccharide storage myopathy (PSSM) in a welldefined
population of affected Quarter Horses, identify
risk factors for PSSM, determine compliance of
owners to dietary and exercise recommendations,
and evaluate the efficacy of dietary and exercise recommendations.
Animals—40 Quarter Horses with PSSM and 37
unaffected control horses.
Procedures—Owners of horses with PSSM completed
a retrospective questionnaire concerning their
Results—Between horses with PSSM and control
horses, no significant differences were found in sex
distribution (21 vs 15 females and 16 vs 22 males,
respectively), temperament, muscle build, diet, or
amount of turnout. In horses with PSSM, signs of
muscle stiffness, muscle fasciculations, sweating,
exercise intolerance, weakness, muscle wasting,
reluctance to move, colic, abnormal gait, recumbency,
lameness, and swollen muscles began between the
age of 1 day and 14 years (mean age, 4.9 ± 3.5 years).
Five horses with PSSM developed acute muscle atrophy.
Sixty-three percent (25/40) of owners fed the recommended
diet, 55% (22/40) provided regular exercise,
and 40% (16/40) followed both dietary and exercise
recommendations. Owners of affected horses
for which a decrease in severity or frequency of
PSSM was not found did not follow the exercise,
dietary, or both recommendations. All horses for
which both dietary and exercise recommendations
were followed had improvement in signs of PSSM.
Conclusions and Clinical Relevance—In addition to
exertional rhabdomyolysis, signs of PSSM include
acute muscle atrophy and gait abnormalities. It
appears that PSSM can be managed by following
dietary recommendations combined with gradual
increases in daily exercise. (Am J Vet Res 2003; 64:1319–1327)
Objective—To measure and compare insulin secretion and sensitivity in healthy alpacas and llamas via glucose clamping techniques.
Animals—8 llamas and 8 alpacas.
Procedures—Hyperinsulinemic euglycemic clamping (HEC) and hyperglycemic clamping (HGC) were performed on each camelid in a crossover design with a minimum 48-hour washout period between clamping procedures. The HEC technique was performed to measure insulin sensitivity. Insulin was infused IV at 6 mU/min/kg for 4 hours, and an IV infusion of glucose was adjusted to maintain blood glucose concentration at 150 mg/dL. Concentrations of blood glucose and plasma insulin were determined throughout. The HGC technique was performed to assess insulin secretion in response to exogenous glucose infusion. An IV infusion of glucose was administered to maintain blood glucose concentration at 320 mg/dL for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout.
Results—Alpacas and llamas were not significantly different with respect to whole-body insulin sensitivity during HEC or in pancreatic β-cell response during HGC. Alpacas and llamas had markedly lower insulin sensitivity during HEC and markedly lower pancreatic β-cell response during HGC, in comparison with many other species.
Conclusions and Clinical Relevance—New World camelids had lower glucose-induced insulin secretion and marked insulin resistance in comparison with other species. This likely contributes to the disorders of fat and glucose metabolism that are common to camelids.
OBJECTIVE To compare effects of training on conventional and underwater treadmills on fiber properties and metabolic responses of the superficial digital flexor (SDF) and gluteal muscles to high-speed exercise in horses.
SAMPLE 6 unconditioned Quarter Horse–type horses.
PROCEDURES 6 horses were walked on underwater and conventional treadmills for 5 d/wk (maximum, 40 min/d) for 8 weeks in a randomized crossover design (60-day detraining period). Horses underwent a standardized exercise test (SET) at high speed before and after training. Analyte concentrations and fiber characteristics were measured in muscle biopsy specimens obtained from horses before and after each SET.
RESULTS Lactate concentration increased 2- to 3-fold in SDF and gluteal muscle after SETs. No training effect was identified on muscle fiber type composition, type II fiber diameter, muscle analyte concentrations, blood lactate concentration, or heart rate responses. Maximum diameters of type I fibers decreased significantly in gluteal muscle with conventional treadmill training and decreased in SDF muscle with both types of training, with maximum diameters greater for horses after underwater versus conventional treadmill training. No change was identified in minimum fiber diameters.
CONCLUSIONS AND CLINICAL RELEVANCE SETs involving near-maximal exertion resulted in an anaerobic response in SDF and gluteal muscles of horses. Eight weeks of conventional or underwater treadmill training resulted in minor changes in type I muscle fiber sizes, with no effect on muscle metabolic or heart rate responses to SETs. After rehabilitation involving underwater treadmills, training at progressing speeds is recommended for horses to develop the required fitness for speed work.
Objective—To determine prevalences of polysaccharide
storage myopathy (PSSM) and shivers in Belgian
Draft Horses (BDHs) and determine whether there
was an association between these 2 conditions.
Design—Prospective cohort study.
Animals—103 BDHs > 1 year old.
Procedure—Owners were questioned regarding clinical
signs of PSSM, shivers, and hindquarter weakness,
defined as poor hindquarter muscling and lack
of propulsion. Blood samples were collected for
determination of serum creatine kinase and aspartate
transferase activities and serum selenium and vitamin
E concentrations. A biopsy sample from the gluteus
medius muscle was submitted for histologic, histochemical,
and biochemical analysis. A diagnosis of
PSSM was made if abnormal amylase-resistant polysaccharide
inclusions were seen histologically.
Results—37 (36%) horses had PSSM and 19 (18%)
had shivers, but only 6 (6%) had both PSSM and shivers,
whereas 31 (30%) had PSSM alone, 13 (13%)
had shivers alone, and 53 (51%) had neither, and a
significant association between PSSM and shivers
was not detected. Hindquarter weakness was found
in 30 horses. Only 13 of 37 (35%) horses with PSSM
and 11 of 19 (58%) horses with shivers had hindquarter
weakness. Serum creatine kinase and aspartate
transferase activities and serum selenium and vitamin
E concentrations were not significantly different
between horses with and without PSSM or between
horses with and without shivers.
Conclusions and Clinical Relevance—Results suggest
that PSSM and shivers are common but unrelated
disorders in BDHs. (J Am Vet Med Assoc 2005;227:1958–1964)
Objective—To determine the maximum amount of flexion and extension of the carpal, tarsal, metacarpophalangeal, and metatarsophalangeal joints and the percentage duration of the stance and swing phases of the stride for horses walking on an underwater treadmill in various water depths.
Animals—9 healthy adult horses.
Procedures—Zinc oxide markers were placed on the forelimbs and hind limbs of the horses. Video was recorded of horses walking (0.9 m/s) on an underwater treadmill during baseline conditions (< 1 cm of water) or in various amounts of water (level of the metatarsophalangeal, tarsal, and stifle joints). Maximum amount of joint flexion and extension, range of motion (ROM), and the percentage durations of the stance and swing phases of the stride were determined with 2-D motion analysis software.
Results—The ROM was greater for all evaluated joints in any amount of water versus ROM for joints in baseline conditions (primarily because of increases in amount of joint flexion). The greatest ROM for carpal joints was detected in a tarsal joint water depth, for tarsal joints in a stifle joint water depth, and for metacarpophalangeal and metatarsophalangeal joints in metatarsophalangeal and tarsal joint water depths. As water depth increased, the percentage durations of the stance and swing phases of the stride significantly decreased and increased, respectively.
Conclusions and Clinical Relevance—Results of this study suggested that exercise on an underwater treadmill is useful for increasing the ROM of various joints of horses during rehabilitation and that the depth of water affects the amount of flexion and extension of joints.
Case Description—20 alpaca crias (13 females and 7 males) were examined for diarrhea (n = 20), weight loss (15), and poor appetite (5). Fourteen crias were between 8 and 18 days of age at time of admission.
Clinical Findings—Cryptosporidiosis was diagnosed in all crias. Common biochemical abnormalities included acidemia, hyperlactemia, azotemia, and hyperglycemia and increases in aspartate transaminase and γ-glutamyltransferase activities. Serum sodium and chloride concentrations were high or low. Other potential gastrointestinal tract pathogens were identified in only 7 crias.
Treatment and Outcome—Supportive care was instituted, including IV administration of fluids with partial parenteral administration of nutrients (n = 19 crias), antimicrobials (19), supplemental orally administered nutrients (11), administration of plasma (10), and insulin treatment (9). Other palliative treatments used by attending clinicians were sucralfate, flunixin meglumine, vitamin A/D/E/B complex, antiparasitic agents, antidiarrheal agents, and azithromycin. Three crias with inadequate urine production and severe azotemia were treated with furosemide administered IV as a bolus or as a constant-rate infusion. Treatment resulted in a successful outcome in 16 of 20 crias. Weight loss and refractory azotemia were common in nonsurvivors but not in surviving crias.
Clinical Relevance—Findings suggested that Cryptosporidium spp may be a diarrheal pathogen of unweaned alpaca crias that may be more widespread than has been recognized and can become endemic on some farms. Metabolic derangements were unpredictable and should be determined by biochemical analysis before fluid and electrolyte replacement is initiated. Cryptosporidiosis has zoonotic potential, and the infection can be self-limiting in alpacas receiving supportive treatment.
Objective—To characterize clinical findings, outcomes, muscle characteristics, and serum or muscle concentrations of α-tocopherol for horses with vitamin E–responsive signs of muscle atrophy and weakness consistent with signs of equine motor neuron disease (EMND).
Design—Retrospective case-control study.
Animals—8 affected (case) adult horses with acute (n = 3) or chronic (5) gross muscle atrophy that improved with vitamin E treatment and 14 clinically normal (control) adult horses with adequate (within reference range; 8) or low (6) muscle concentrations of α-tocopherol.
Procedures—Medical records were reviewed, serum and muscle concentrations of α-tocopherol were measured, and frozen biopsy specimens of sacrocaudalis dorsalis medialis muscle and gluteal muscle were histologically evaluated for pathological changes. Fiber type composition and fiber diameters were assessed in gluteal muscle specimens.
Results—A myopathy that was histologically characterized by redistribution of mitochondrial enzyme stain (moth-eaten appearance) and anguloid atrophy of myofibers was evident in sacrocaudalis dorsalis medialis muscle fibers of the 8 affected horses that had low serum (6/8) or skeletal muscle (5/5) concentrations of α-tocopherol; these histopathologic changes were not found in muscle specimens of control horses with low or adequate muscle concentrations of α-tocopherol. All affected horses regained strength and muscle mass within 3 months after initiation of vitamin E treatment and dietary changes.
Conclusions and Clinical Relevance—A vitamin E–deficient myopathy characterized histologically by a moth-eaten appearance in the mitochondria and anguloid myofiber atrophy in frozen sections of sacrocaudalis dorsalis medialis muscle biopsy specimens was found in horses with clinical signs of EMND that were highly responsive to vitamin E treatment. This myopathy may be a specific syndrome or possibly precede the development of neurogenic muscle fiber atrophy typical of EMND.
Objective—To determine effects of dexamethasone
on insulin sensitivity, serum creatine kinase (CK) activity
4 hours after exercise, and muscle glycogen concentration
in Quarter Horses with polysaccharide storage
Animals—4 adult Quarter Horses with PSSM.
Procedure—A 2 × 2 crossover design was used with
dexamethasone (0.08 mg/kg) or saline (0.9% NaCl)
solution administered IV every 48 hours. Horses were
exercised on a treadmill daily for 3 wk/treatment with
a 2-week washout period between treatments. Serum
CK activity was measured daily 4 hours after exercise.
At the end of each treatment period, serum cortisol
concentrations were measured, a hyperinsulinemic
euglycemic clamp (HEC) technique was performed,
and muscle glycogen content was determined.
Results—Mean ± SEM serum cortisol concentration
was significantly lower after 48 hours for the dexamethasone
treatment (0.38 ± 0.08 mg/dL), compared
with the saline treatment (4.15 ± 0.40 mg/dL).
Dexamethasone significantly decreased the rate of glucose
infusion necessary to maintain euglycemia during
the HEC technique, compared with the saline treatment.
Muscle glycogen concentrations and mean CK
activity after exercise were not altered by dexamethasone
treatment, compared with the saline treatment.
Conclusions and Clinical Relevance—Dexamethasone
significantly reduced whole-body insulin-stimulated
glucose uptake in Quarter Horses with PSSM
after a 3-week period but did not diminish serum CK
response to exercise or muscle glycogen concentrations
in these 4 horses. Therefore, a decrease in glucose
uptake for 3 weeks did not appear to alleviate
exertional rhabdomyolysis in these horses. It is possible
that long-term treatment may yield other results.
(Am J Vet Res 2005;66:1718–1723)
Objective—To determine insulin sensitivity, proportions of muscle fiber types, and activities of glycogenolytic and glycolytic enzymes in Belgians with and without polysaccharide storage myopathy (PSSM).
Animals—10 Quarter Horses (QHs) and 103 Belgians in which PSSM status had been determined.
Procedures—To determine insulin sensitivity, a hyperinsulinemic euglycemic clamp (HEC) technique was used in 5 Belgians with PSSM and 5 Belgians without PSSM. Insulin was infused IV at 3 mU/min/kg for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout. An IV infusion of glucose was administered to maintain blood glucose concentration at 100 mg/dL. Activities of glycogenolytic and glycolytic enzymes were assessed in snap-frozen biopsy specimens of gluteus medius muscle obtained from 4 Belgians with PSSM and 5 Belgians without PSSM. Percentages of type 1, 2a, and 2b muscle fibers were determined via evaluation of ≥ 250 muscle fibers in biopsy specimens obtained from each Belgian used in the aforementioned studies and from 10 QHs (5 with PSSM and 5 without PSSM).
Results—Belgians with and without PSSM were not significantly different with respect to whole-body insulin sensitivity, muscle activities of glycogenolytic and glycolytic enzymes, or proportions of muscle fiber types. However, Belgians had an increased proportion of type 2a and decreased proportion of type 2b muscle fibers, compared with proportions in QHs, regardless of PSSM status.
Conclusions and Clinical Relevance—PSSM in Belgians may be attributable to excessive glycogen synthesis rather than decreased glycogen utilization or enhanced glucose uptake into muscle cells.