Effect of dantrolene premedication on various cardiovascular and biochemical variables and the recovery in healthy isoflurane-anesthetized horses

McKenzie, Erica C.; Concetto, Stefano Di; Payton, Mark E.; Mandsager, Ronald E.; Arko, Matevž

doi:10.2460/ajvr.76.4.293

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Antimuscarinics, such as glycopyrrolate [292] or methoctramine [293], doxapram [296], dimethyl sulfoxide [291] and dantrolene [294], do not seem to affect recovery from anaesthesia in horses. Hypertonic solution 7.2%, typically used as a resuscitation fluid in compromised colics, produces an increase in diuresis characterised by numerous micturitions [297].…”

Section: Other Drugs Used During Maintenancementioning

confidence: 98%

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Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature

Gozalo-Marcilla

Ringer

2021

Animals

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Recovery remains the most dangerous phase of general anaesthesia in horses. The objective of this publication was to perform a structured literature review including levels of evidence (LoE) of each study with the keywords “recovery anaesthesia horse”, entered at once, in the search browsers PubMed and Web of Science. The two authors independently evaluated each candidate article. A final list with 444 articles was obtained on 5 April 2021, classified as: 41 “narrative reviews/expert opinions”, 16 “retrospective outcome studies”, 5 “surveys”, 59 “premedication/sedation and induction drugs”, 27 “maintenance with inhalant agents”, 55 “maintenance with total intravenous anaesthesia (TIVA)”, 3 “TIVA versus inhalants”, 56 “maintenance with partial intravenous anaesthesia (PIVA)”, 27 “other drugs used during maintenance”, 18 “drugs before/during recovery”, 18 “recovery systems”, 21 “respiratory system in recovery”, 41 “other factors”, 51 “case series/reports” and 6 “systems to score recoveries”. Of them, 167 were LoE 1, 36 LoE 2, 33 LoE 3, 110 LoE 4, 90 LoE 5 and 8 could not be classified based on the available abstract. This review can be used as an up-to-date compilation of the literature about recovery after general anaesthesia in adult horses that tried to minimise the bias inherent to narrative reviews.

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Section: Other Drugs Used During Maintenancementioning

confidence: 98%

“…Eight publications reported the effects on recovery of a group of miscellaneous drugs [291][292][293][294][295][296][297][298]. Lee et al, (1998) studied the effects of several cardiovascular stimulant drugs in experimental halothane-anaesthetised ponies [295].…”

Section: Other Drugs Used During Maintenancementioning

confidence: 99%

Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature

Gozalo-Marcilla

Ringer

2021

Animals

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“…Methodologies used to study RER have included caffeineinduced contractures in muscle bundles and muscle cell cultures, Ca 2+ release in isolated sarcoplasmic reticulum membranes (SR) and microarray studies of gene expression [8][9][10][11][12]. Based on a potential dysregulation of Ca 2+ release with RER, dantrolene, an inhibitor of the sarcoplasmic reticulum Ca 2+ release channel (RYR1), has been used prophylactically prior to exercise to decrease muscle degeneration in RER-susceptible Thoroughbreds at doses between approximately 0.8-4 mg/kg [13][14][15][16]. Side effects of dantrolene, including decreased cardiac output and hyperkalemia, are reported in horses when higher doses (6 mg/kg) are given prior to anesthesia [16].…”

Section: Introductionmentioning

confidence: 99%

“…Based on a potential dysregulation of Ca 2+ release with RER, dantrolene, an inhibitor of the sarcoplasmic reticulum Ca 2+ release channel (RYR1), has been used prophylactically prior to exercise to decrease muscle degeneration in RER-susceptible Thoroughbreds at doses between approximately 0.8-4 mg/kg [13][14][15][16]. Side effects of dantrolene, including decreased cardiac output and hyperkalemia, are reported in horses when higher doses (6 mg/kg) are given prior to anesthesia [16]. In a study of two Standardbred trotters that subsequently developed RER, altered flux through the mitochondrial electron transport system was identified and this was proposed to have a role in the etiology of RER [17].…”

Section: Introductionmentioning

confidence: 99%

Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyolysis in Thoroughbred racehorses

et al. 2021

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Recurrent exertional rhabdomyolysis (RER) is a chronic muscle disorder of unknown etiology in racehorses. A potential role of intramuscular calcium (Ca2+) dysregulation in RER has led to the use of dantrolene to prevent episodes of rhabdomyolysis. We examined differentially expressed proteins (DEP) and gene transcripts (DEG) in gluteal muscle of Thoroughbred race-trained mares after exercise among three groups of 5 horses each; 1) horses susceptible to, but not currently experiencing rhabdomyolysis, 2) healthy horses with no history of RER (control), 3) RER-susceptible horses treated with dantrolene pre-exercise (RER-D). Tandem mass tag LC/MS/MS quantitative proteomics and RNA-seq analysis (FDR <0.05) was followed by gene ontology (GO) and semantic similarity of enrichment terms. Of the 375 proteins expressed, 125 were DEP in RER-susceptible versus control, with 52 ↑DEP mainly involving Ca2+ regulation (N = 11) (e.g. RYR1, calmodulin, calsequestrin, calpain), protein degradation (N = 6), antioxidants (N = 4), plasma membranes (N = 3), glyco(geno)lysis (N = 3) and 21 DEP being blood-borne. ↓DEP (N = 73) were largely mitochondrial (N = 45) impacting the electron transport system (28), enzymes (6), heat shock proteins (4), and contractile proteins (12) including Ca2+ binding proteins. There were 812 DEG in RER-susceptible versus control involving the electron transfer system, the mitochondrial transcription/translational response and notably the pro-apoptotic Ca2+-activated mitochondrial membrane transition pore (SLC25A27, BAX, ATP5 subunits). Upregulated mitochondrial DEG frequently had downregulation of their encoded DEP with semantic similarities highlighting signaling mechanisms regulating mitochondrial protein translation. RER-susceptible horses treated with dantrolene, which slows sarcoplasmic reticulum Ca2+ release, showed no DEG compared to control horses. We conclude that RER-susceptibility is associated with alterations in proteins, genes and pathways impacting myoplasmic Ca2+ regulation, the mitochondrion and protein degradation with opposing effects on mitochondrial transcriptional/translational responses and mitochondrial protein content. RER could potentially arise from excessive sarcoplasmic reticulum Ca2+ release and subsequent mitochondrial buffering of excessive myoplasmic Ca2+.

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Anesthetic Management for Muscular Conditions

McKenzie¹,

Clark‐Price²

2022

Equine Anesthesia and Co‐Existing Disease

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Effect of dantrolene premedication on various cardiovascular and biochemical variables and the recovery in healthy isoflurane-anesthetized horses

Abstract: Results suggested that dantrolene premedication prevented muscle damage without affecting anesthetic recovery but impaired CO and precipitated hyperkalemia and cardiac arrhythmias in healthy isoflurane-anesthetized horses.

Cited by 7 publications

References 28 publications

Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature

Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature

Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyolysis in Thoroughbred racehorses

Anesthetic Management for Muscular Conditions

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