Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.
Abstract: To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). Methods: 2 healthy horses and 5 Thoroughbreds with RER. Methods: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, Results: 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. Conclusions: In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.
Publication Date: 2004-01-15 PubMed ID: 14719706DOI: 10.2460/ajvr.2004.65.74Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study looks into how giving dantrolene sodium orally to horses affected their serum creatine kinase (CK) activity after exercise, particularly in horses with recurrent exertional rhabdomyolysis (RER). It found that this drug helped lower serum CK activity in four out of five horses with RER.
Methods
- At the start, the research involved two horses that were healthy and five Thoroughbreds that had RER. Three horses, had two doses of dantrolene (which was 4, 6, or 8 mg/kg administered orally) two days apart with and without food withdrawal.
- Plasma dantrolene concentrations were measured through spectrofluorometric methods 90 minutes after each dosage. This was done to find out exactly how much of the drug was present in the horses’ system.
- Based on the initial results, dantrolene or a control treatment (water) was administered orally to five Thoroughbreds with RER from which the food had been withheld. This was done 90 minutes before they were asked to exercise on a treadmill for 30 minutes, five days a week, over two three-week periods.
- The level of serum CK activity was determined 4 hours after each exercise session. This was a way of gauging how much the horses’ muscles broke down due to both exertion and RER.
Results
- Plasma dantrolene concentrations were 0.62 +/- 0.13 micrograms per milliliter in the dantrolene treatment group, while in the control group, the levels were 0 micrograms per milliliter, 90 minutes post the dantrolene dosage.
- It was found that the serum CK activity was significantly lower in the horses given dantrolene (264 +/- 13 U/L) as compared to the horses given water (1,088 +/- 264 U/L).
- Two Horses showed significant muscle stiffness after being administered the control treatment.
Conclusion
- The results indicated that administering 4 mg of dantrolene per kilogram orally provided variable but measurable plasma concentrations, which significantly reduced the serum CK activity after exercise in four out of the five horses suffering from RER, which the food has been withheld.
Cite This Article
APA
McKenzie EC, Valberg SJ, Godden SM, Finno CJ, Murphy MJ.
(2004).
Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.
Am J Vet Res, 65(1), 74-79.
https://doi.org/10.2460/ajvr.2004.65.74 Publication
Researcher Affiliations
- Department of Clinical and Population Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA.
MeSH Terms
- Administration, Oral
- Animals
- Creatine Kinase / antagonists & inhibitors
- Creatine Kinase / blood
- Creatine Kinase / drug effects
- Cross-Over Studies
- Dantrolene / administration & dosage
- Food Deprivation
- Horse Diseases / blood
- Horse Diseases / physiopathology
- Horses
- Muscle Relaxants, Central / administration & dosage
- Physical Exertion / physiology
- Rhabdomyolysis / blood
- Rhabdomyolysis / physiopathology
- Rhabdomyolysis / veterinary
Citations
This article has been cited 7 times.- Aldrich K, Velez-Irizarry D, Fenger C, Schott M, Valberg SJ. Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyolysis in Thoroughbred racehorses. PLoS One 2021;16(2):e0244556.
- Story MR, Haussler KK, Nout-Lomas YS, Aboellail TA, Kawcak CE, Barrett MF, Frisbie DD, McIlwraith CW. Equine Cervical Pain and Dysfunction: Pathology, Diagnosis and Treatment. Animals (Basel) 2021 Feb 6;11(2).
- Autry JM, Karim CB, Perumbakkam S, Finno CJ, McKenzie EC, Thomas DD, Valberg SJ. Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle. Vet Sci 2020 Nov 13;7(4).
- Breed D, Meyer LCR, Steyl JCA, Goddard A, Burroughs R, Kohn TA. Conserving wildlife in a changing world: Understanding capture myopathy-a malignant outcome of stress during capture and translocation. Conserv Physiol 2019;7(1):coz027.
- Fernandez-Fuente M, Terracciano CM, Martin-Duque P, Brown SC, Vassaux G, Piercy RJ. Calcium homeostasis in myogenic differentiation factor 1 (MyoD)-transformed, virally-transduced, skin-derived equine myotubes. PLoS One 2014;9(8):e105971.
- Haraschak JL, Langston VC, Wang R, Riggs C, Fellman C, Ross MK, Bulla C, Lunsford K, Mackin A, Archer T. Pharmacokinetic evaluation of oral dantrolene in the dog. J Vet Pharmacol Ther 2014 Jun;37(3):286-94.
- Isgren CM, Upjohn MM, Fernandez-Fuente M, Massey C, Pollott G, Verheyen KL, Piercy RJ. Epidemiology of exertional rhabdomyolysis susceptibility in standardbred horses reveals associated risk factors and underlying enhanced performance. PLoS One 2010 Jul 14;5(7):e11594.
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