Post anesthetic myositis in the horse associated with in vitro malignant hyperthermia susceptibility

Waldron-Mease, E; Rosenberg, Henry

doi:10.1007/bf02268950

Cited by 19 publications

(9 citation statements)

References 6 publications

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“…Both conditions have clinical and pathophysiological features in common with MH syndromes and with each other (Arighi et al, 1984;Hodgson, 1985;Waldron-Mease, 1978). Exaggerated skeletal muscle contraction responses to caffeine and halothane have been reported for a number of horses that Dantrohe in horses 219 recovered from equine PAM (Waldron-Mease & Rosenberg, 1979;Waldron-Mease et al, 1981). Controlled studies of the efficacy of dantrolene in these conditions have yet to be performed, but clinical evidence to date is favorable (Hodgson, 1985;Short & White, 1978;Waldron-Mease & Rosenberg, 1979;Waldron-Mease et al, 1981).…”

Section: ;mentioning

confidence: 95%

Pharmacokinetics of dantrolene sodium in horses

Court

Engelking

Dodman

et al. 1987

Vet Pharm & Therapeutics

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The pharmacokinetics of dantrolene sodium were investigated in horses following both intravenous (2 mg/kg) and intragastric (4 mg/kg) administration. Two ponies also received dantrolene sodium intravenously (2 mg/kg) in a pilot study to obtain preliminary kinetic data and to determine urinary and biliary excretion of the intact drug. Distribution and elimination of dantrolene was rapid, resulting in an elimination half-life of 129 +/- 8 (SEM) min and a whole body clearance of 4.16 +/- 0.52 ml/min/kg. Following intragastric administration, dantrolene rapidly acheived peak concentrations within 1.5 h, but was incompletely absorbed, with a bioavailability of 39 +/- 10%. Small amounts of intact drug were recovered in urine and bile. Based upon disposition kinetics of dantrolene in these studies, intravenous and intragastric dosage regimens were determined which would maintain blood dantrolene concentrations within the predicted clinically effective range.

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Section: ;mentioning

confidence: 95%

Pharmacokinetics of dantrolene sodium in horses

Court

Engelking

Dodman

et al. 1987

Vet Pharm & Therapeutics

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“…16,21,37,43 or abnormalities in the in vitro contracture test using halothane, succinylcholine, and caffeine. 13,32,42 The prevalence of the MH genotype in humans is about 1:15,000 in children and 1:50,000 in adults. 9 Although the incidence of MH in horses is unknown, in view of the low number of case reports, it appears…”

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confidence: 99%

Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia

et al. 2004

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Equine malignant hyperthermia MH has been suspected but never genetically confirmed. In this study, we investigated whether mutations in a candidate gene, RyR1, were associated with MH in two clinically affected horses. RyR1 gene sequences revealed polymorphisms in exons 15, 17, and 46 in WTRyR1 and MHRyR1 horses with one derived amino acid change in MHRyR1 exon 46, R2454G. The MHRyR1 horses were genetically heterozygous for this mutation, but presented an MH phenotype with halothane challenge. Skeletal sarcoplasmic reticulum from a R2454G heterozygote collected during a fulminant MH episode showed significantly higher affinity and density of [3H]ryanodine-binding sites compared to WTRyR1, but no differences in Ca2+, Mg2+, and caffeine modulation. In conclusion, an autosomal missense mutation in RyR1 is associated with MH in the horse, providing a screening test for susceptible individuals. [3H]ryanodine-binding analysis suggests that long-lasting changes in RyR1 conformation persists in vitro after the triggering event.

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“…The 1st report of the disease in horses occurred in 1975, 8 and since then other cases have been documented 9–19 . Reported breeds include Quarter Horse, Thoroughbred, Appaloosa, Arabian, and ponies.…”

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confidence: 99%

“…1 The 1st report of the disease in horses occurred in 1975, 8 and since then other cases have been documented. [9][10][11][12][13][14][15][16][17][18][19] Reported breeds include Quarter Horse, Thoroughbred, Appaloosa, Arabian, and ponies. The clinical signs manifested on exposure to triggering agents are similar to those described in humans.…”

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confidence: 99%

Malignant Hyperthermia Associated with Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

Aleman¹,

Nieto²,

Magdesian³

2009

Veterinary Internal Medicne

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Background: Anesthetic-induced malignant hyperthermia (MH) has been documented in Quarter Horses with a single point mutation in the ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. However, there have been no reports of nonanesthetic manifestations of MH in horses with the C7360G mutation.Objective: To describe clinical manifestations of Quarter Horses with the C7360G mutation. Animals: Eleven Quarter Horses with the RyR1 C7360G mutation.Methods: This prospective study included horses with suspected MH, undetermined etiology of sudden death, death within hours of onset of rhabdomyolysis, muscle rigidity, stiffness, intermittent sweating, and persistent increases in serum muscle enzyme activities. Whole blood in EDTA and skeletal muscle were processed for genetic and histochemical analysis. Medical records and pedigrees were collected when available.Results: Both anesthetic-and non-anesthetic-associated myopathic manifestations of MH occurred in halter Quarter Horses with mutation of RyR1. The disease is inherited as an autosomal dominant trait. Clinical and laboratory abnormalities were similar in both forms. Rhabdomyolysis was a common finding in both groups of horses. Skeletal muscle histochemical findings were nonspecific and compatible with a noninflammatory myopathic process.Conclusions and Clinical Importance: MH is a potentially fatal disease of Quarter Horses that could be triggered by halogenated anesthetics and other nonanesthetic factors that may include exercise, stress, breeding, illnesses, and concurrent myopathies.

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Post anesthetic myositis in the horse associated with in vitro malignant hyperthermia susceptibility

Cited by 19 publications

References 6 publications

Pharmacokinetics of dantrolene sodium in horses

Pharmacokinetics of dantrolene sodium in horses

Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia

Malignant Hyperthermia Associated with Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

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