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- Author or Editor: Johannes H. van der Kolk x
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Abstract
Objectives—To acquire reference range values indicative of glucose metabolism by use of the hyperglycemic clamp technique in healthy horses and evaluate the usefulness of the euglycemic hyperinsulinemic clamp technique in healthy horses and ponies.
Animals—5 Dutch Warmblood horses and 4 Shetland ponies.
Procedure—The hyperglycemic clamp technique was used for quantification of the sensitivity of beta cells to exogenous glucose infusion in horses. The euglycemic hyperinsulinemic clamp technique was used to determine the sensitivity and responsiveness of tissues to exogenous insulin in horses and ponies.
Results—During the hyperglycemic clamp technique, the mean amount of glucose metabolized (M) in horses was 0.011 ± 0.0045 mmol/kg·min–1 (95% confidence interval [CI], 0.0018 to 0.020 mmol/kg·min–1; range, 0.000035 to 0.021 mmol/kg·min–1) and the mean M value-to-plasma insulin concentration (I) ratio (ie, mmol of glucose/kg·min–1 per pmol of insulin/L X 100) was 0.017 ± 0.016 (95% CI, –0.014 to 0.049; range, 0.000025 to 0.055). During the euglycemic hyperinsulinemic clamp technique, the mean M value was 0.014 ± 0.0055 mmol/kg·min–1 (95% CI, 0.0026 to 0.025 mmol/kg·min–1; range, 0.0042 to 0.023 mmol/kg·min–1) in horses and 0.0073 ± 0.0020 mmol/kg·min–1 (95% CI, 0.0034 to 0.011 mmol/kg·min–1; range, 0.0049 to 0.011 mmol/kg·min–1) in ponies. The M value was significantly lower in ponies than in horses, whereas the M:I ratios were not significantly different between horses and ponies.
Conclusion and Clinical Relevance—Glucose clamp techniques offer good methods to investigate glucose metabolism in horses and ponies. A higher degree of insulin resistance was found in ponies, compared with Dutch Warmblood horses. (Am J Vet Res 2003;64: 1260–1264)
Abstract
Objective—To investigate the effects of exercise on activation of mitogen-activated protein kinase (MAPK) signaling proteins in horses.
Animals—6 young trained Standardbred geldings.
Procedure—Horses performed a 20-minute bout of exercise on a treadmill at 80% of maximal heart rate. Muscle biopsy specimens were obtained from the vastus lateralis and pectoralis descendens muscles before and after exercise. Amount of expression and intracellular location of phosphospecific MAPK pathway intermediates were determined by use of western blotting and immunofluorescence staining.
Results—Exercise resulted in a significant increase in phosphorylation of p38 pathway intermediates, c-Jun NH2 terminal kinase (JNK), and heat shock protein 27 (HSP27) in the vastus lateralis muscle, whereas no significant changes were found in phosphorylation of extracellular regulated kinase. In the pectoralis descendens muscle, phosphorylation of p38 and HSP27 was significantly increased after exercise. Immunohistochemical analysis revealed fiber-type– specific locations of phosphorylated JNK in type 2a/b intermediate and 2b fibers and phosphorylated p38 in type 1 fibers. Phosphorylated HSP27 was strongly increased after exercise in type 1 and 2a fibers.
Conclusions and Clinical Relevance—The p38 pathway and JNK are activated in the vastus lateralis muscle after a single 20-minute bout of submaximal exercise in trained horses. Phosphorylation of HSP27 as detected in the study reported here is most likely induced through the p38 signaling pathway.
Abstract
Objective—To investigate the effects of acute exercise and long-term training on Na+,K+-ATPase content, mRNA isoforms, and protein concentration in equine muscle.
Animals—6 Standardbreds.
Procedures—Horses performed a bout of exercise on a treadmill before and after 18 weeks of combined interval and endurance training. Muscle biopsy specimens were obtained from vastus lateralis muscle (VLM) and pectoralis descendens muscle (PDM) before and after exercise. The Na+,K+-ATPase content, mRNA isoforms, and protein concentrations were determined by use of [3H]ouabain binding, real-time PCR assay, and western blotting, respectively.
Results—6 Na+,K+-ATPase mRNA isoforms were present in equine muscle, but only A2 and B1 proteins were detected. Exercise before training resulted in increases of mRNA isoforms A1, A2, A3, and B2 in VLM and A1 and B3 in PDM. Training increased resting values for mRNA isoforms A3 and B1 in VLM and B3 in PDM. The Na+,K+-ATPase, [3H]ouabain binding, and proteins of mRNA A2 and B1 increased in VLM, whereas in PDM, only A2 protein increased as a result of training. After training, effects of strenuous exercise on mRNA expression were no longer detectable.
Conclusions and Clinical Relevance—Equine muscle contained all Na+,K+-ATPase mRNA isoforms, but only A2 and B1 proteins could be detected. Expression of these isoforms changed as a result of strenuous exercise and long-term training, representing an adaptive response. Determination of Na+,K+-ATPase gene expression may be relevant for understanding alterations in excitability during neuromuscular diseases.
Abstract
OBJECTIVE To determine effects of anesthesia on plasma concentrations and pulsatility of ACTH in samples obtained from the cavernous sinus and jugular vein of horses.
ANIMALS 6 clinically normal adult horses.
PROCEDURES Catheters were placed in a jugular vein and into the cavernous sinus via a superficial facial vein. The following morning (day 1), cavernous sinus blood samples were collected every 5 minutes for 1 hour (collection of first sample = time 0) and jugular venous blood samples were collected at 0, 30, and 60 minutes. On day 2, horses were sedated with xylazine hydrochloride and anesthesia was induced with propofol mixed with ketamine hydrochloride. Horses were positioned in dorsal recumbency. Anesthesia was maintained with isoflurane in oxygen and a continuous rate infusion of butorphanol tartrate. One hour after anesthesia was induced, the blood sample protocol was repeated. Plasma ACTH concentrations were quantified by use of a commercially available sandwich assay. Generalized estimating equations that controlled for horse and an expressly automated deconvolution algorithm were used to determine effects of anesthesia on plasma ACTH concentrations and pulsatility, respectively.
RESULTS Anesthesia significantly reduced the plasma ACTH concentration in blood samples collected from the cavernous sinus.
CONCLUSIONS AND CLINICAL RELEVANCE Mean plasma ACTH concentrations in samples collected from the cavernous sinus of anesthetized horses were reduced. Determining the success of partial ablation of the pituitary gland in situ for treatment of pituitary pars intermedia dysfunction may require that effects of anesthesia be included in interpretation of plasma ACTH concentrations in cavernous sinus blood.
Abstract
Objective—To determine the influence of intensified training and subsequent reduced training on glucose metabolism rate and peripheral insulin sensitivity in horses and identify potential markers indicative of early overtraining.
Animals—12 Standardbred geldings.
Procedures—Horses underwent 4 phases of treadmill-based training. In phase 1, horses were habituated to the treadmill. In phase 2, endurance training was alternated with high-intensity exercise training. In phase 3, horses were divided into control and intensified training groups. In the intensified training group, training intensity, duration, and frequency were further increased via a protocol to induce overtraining; in the control group, these factors remained unaltered. In phase 4, training intensity was reduced. Standardized exercise tests were performed after each phase and hyperinsulinemic euglycemic clamp (HEC) tests were performed after phases 2, 3, and 4.
Results—10 of 12 horses completed the study. Dissociation between mean glucose metabolism rate and mean glucose metabolism rate-to-plasma insulin concentration ratio (M:I) was evident in the intensified training group during steady state of HEC testing after phases 3 and 4. After phase 4, mean glucose metabolism rate was significantly decreased (from 31.1 ± 6.8 μmol/kg/min to 18.1 ± 3.4 μmol/kg/min), as was M:I (from 1.05 ± 0.31 to 0.62 ± 0.17) during steady state in the intensified training group, compared with phase 3 values for the same horses.
Conclusions and Clinical Relevance—Dissociation between the glucose metabolism rate and M:I in horses that underwent intensified training may reflect non-insulin–dependent increases in glucose metabolism.
Abstract
Objective—To compare the effects of administration of 2 volumes of a calcium solution (calcium oxide and calcium gluconate) on plasma ionized calcium concentration (PICaC) and clinical recovery from naturally occurring hypocalcemia (NOHC; milk fever) in lactating dairy cows.
Animals—123 cows with NOHC (PICaC < 0.95 mmol/L [3.81 mg/dL]) and 20 clinically normal control cows.
Procedures—Affected cows were treated IV once or repeatedly with 450 (n = 56) or 750 mL (67) of calcium solution (1.65 g of calcium/100 mL) until clinical recovery was achieved. The PICaC was assessed 48 hours after the first treatment or after the treatment that achieved clinical recovery. Biochemical recovery was defined as PICaC ≥ 0.95 mmol/L. Plasma from control cows was used for PICaC reference range determination. Plasma samples from both groups were assessed after storage for 20 days at 20°C.
Results—The PICaC reference range derived from blood collected in tubes containing lithium heparin was 1.02 to 1.29 mmol/L (4.09 to 5.17 mg/dL). Following storage, plasma samples were suitable for PICaC assessment. All cows treated with ≥ 1 volume of 450 and 750 mL of calcium solution recovered clinically; however, 31 of 83 (37%) evaluated cows were not biochemically recovered at 48 hours following treatment. Only cows with PICaC < 0.48 mmol/L (1.92 mg/dL) before the first treatment had to be treated ≥ 3 times.
Conclusions and Clinical Relevance—Results did not support the need to increase the administered volume of calcium solution from 450 to 750 mL for treatment of NOHC in dairy cows.
Abstract
Objective—To determine the effects of short-term IV administration of hydrocortisone or equine growth hormone (eGH) or long-term IM administration of eGH to horses on tissue sensitivity to exogenous insulin.
Animals—5 Standardbreds and 4 Dutch Warmblood horses.
Procedure—The euglycemic-hyperinsulinemic clamp technique was used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 µg/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined.
Results—Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution.
Conclusions and Clinical Relevance—Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states. In contrast, long-term administration of eGH decreased tissue sensitivity to exogenous insulin associated with hyperinsulinemia. Therefore, increased concentrations of growth hormone may contribute to insulin resistance in horses with various disease states. (Am J Vet Res 2005;66:1907–1913)
Abstract
Objective—To compare the effects of IV administration of various doses of ovine corticotrophin–releasing hormone (oCRH) on plasma and saliva cortisol concentrations in healthy horses and determine whether an oCRH challenge test protocol is valid for use in adult horses.
Animals—24 healthy Warmblood horses.
Procedures—Each horse received oCRH in saline (0.9% NaCl) via IV administration at a dose of 0 (control treatment), 0.01, 0.1, or 1.0 Mg/kg (6 horses/group). Jugular blood and saliva samples were collected simultaneously 15 minutes before and immediately prior to injection (baseline); data from these samples were pooled to provide basal values. Subsequently, 14 postinjection blood and saliva samples were both collected within a 210-minute period. Cortisol concentrations in all samples were assessed via a solid-phase radioimmunoassay.
Results—All doses of oCRH induced significant increases from baseline in both plasma and salivary cortisol concentrations. Compared with the smaller doses of oCRH, the 1.0 Mg/kg dose of oCRH induced significantly greater plasma cortisol concentrations. A relationship (r = 0.518) between basal cortisol concentrations in plasma and saliva was detected.
Conclusions and Clinical Relevance—For use as a CRH challenge test in adult horses, a protocol involving IV administration of a dose of at least 0.01 Mg of oCRH/kg and postinjection collection of blood samples from 10 to 180 minutes and saliva samples from 20 to 50 minutes for assessment of plasma and saliva cortisol concentrations should be sufficient. Application of such a test might be helpful to detect states of chronic activation of the hypothalamo-pituitary-adrenocortical axis at the hypothalamic level.
Abstract
Objective—To determine whether electromyographic abnormalities are evident in skeletal muscles in horses with induced hypocalcemia and hypomagnesemia.
Animals—7 healthy adult Dutch Warmblood horses.
Procedure—Electromyographic examination was performed in the lateral vastus, triceps, and subclavian muscles before and after IV infusion of EDTA. An initial dose (mean ± SD, 564 ± 48 ml) of a 10% solution of sodium EDTA was administered IV during a period of 21 ± 7.3 minutes to establish a blood concentration of ionized calcium of approximately 0.5 mMol/L. Average rate of EDTA infusion to maintain ionized calcium at this concentration was 6.6 ml/min.
Results—Mean blood concentrations of ionized calcium and magnesium were 1.39 ± 0.06 and 0.84 ± 0.09 mM, respectively before EDTA infusion; after EDTA infusion, concentrations were 0.48 ± 0.05 and 0.44 ± 0.20 mM, respectively. This state induced positive waves; fibrillation potentials; doublets, triplets, and multiplets; complex repetitive discharges; and neuromyotonia. Analysis of motor unit action potentials (MUAP) after EDTA infusion revealed an increase in prevalence of polyphasic and complex MUAP in all muscles.
Conclusion and Clinical Relevance—None of the horses had classical signs of hypocalcemia and hypomagnesemia. In contrast, all horses had spontaneous activity in the measured muscles indicative of nerve hyperirritability. Calcium and magnesium deficits appear to have consequences, which may be subclinical, affecting functions of the neuromuscular system. This is of interest for equestrian sports in which hypocalcemia and hypomagnesemia are expected, such as during endurance rides. (Am J Vet Res 2002;63:849–856)
Abstract
Objectives—To determine whether increased glucose metabolism is the potential cause of the decreased plasma glucose curve determined after oral glucose tolerance testing in horses with lower motor neuron degeneration.
Animals—3 horses with signs suggestive of lower motor neuron degeneration, 1 horse with malignant melanoma with multiple metastases, and an obese but otherwise healthy horse.
Procedures—Glucose metabolism was assessed by use of the hyperglycemic clamp and euglycemic hyperinsulinemic clamp techniques.
Results—Mean rate of glucose metabolism of horses with lower motor neuron degeneration was significantly greater (mean, 3.7 times greater than control horses; range, 2.1 to 4.8 times greater) than that reported in 5 healthy control horses (41 ± 13 µmol/kg/min vs 11 ± 4.5 µmol/kg/min, respectively). In addition, one of the affected horses, an 8-year-old warmblood gelding, had a 5.6- times increased sensitivity to exogenously administered insulin, compared with that reported in 5 healthy control horses. Pancreatic insulin secretion was not insufficient in horses with lower motor neuron degeneration. Findings in the 2 diseased control horses were unremarkable.
Conclusions and Clinical Relevance—Increased glucose metabolism in horses with lower motor neuron degeneration may be the cause of the decreased plasma glucose curve detected after oral glucose tolerance testing. This finding could aid in developing supportive treatments with respect to adequate glucose and vitamin E supplementation. (Am J Vet Res 2005;66:271–276)