Edwards J G T, Newtont J R, Ramzan P H L, Pilsworth R C, Shepherd M C
Rossdale and Partners, Beaufort Cottage Stables, High Street, Newmarket, Suffolk CB8 8JS, UK.
Equine Vet J. 2003 Nov;35(7):707-11. doi: 10.2746/042516403775696221.
Dantrolene sodium (Dantrium) has been used extensively for the treatment of myopathies in man and anecdotal evidence suggests it is of clinical benefit in the control of exercise-induced rhabdomyolysis (ER) in racehorses, although data to support this are currently lacking.
To investigate the efficacy of oral dantrolene sodium in controlling ER in a randomised, double-blind, placebo-controlled crossover trial involving 77 Thoroughbred racehorses in Newmarket, UK.
Horses were treated on 2 occasions 1 week apart, with treatment days coinciding with a return to exercise following 2 days box rest on each occasion. For the first treatment, each horse was randomly selected to receive either 800 mg dantrolene sodium or a colour-matched placebo administered orally 1 h before exercise. This was followed by crossover to the other treatment on the second occasion, with each horse thereby acting as its own control. Degree of ER was assessed using rising serum creatine kinase (CK) levels, by subtracting pre-exercise blood CK levels from those measured in 6 h post exercise blood samples. For each horse, the difference in change between pre- and post exercise CK values between placebo and dantrolene treatments was calculated, with positive values indicating a greater rise with placebo than with dantrolene sodium treatment.
The overall mean difference for all horses was +104.8 iu/l and the null hypothesis, that there was no true difference in non-normally distributed post exercise rises in CK values between placebo and dantrolene treatments, was rejected (P = 0.0013) using the nonparametric Wilcoxon signed rank test. Additionally, no horses given dantrolene sodium showed clinical signs of ER, whereas 3 horses given the placebo developed ER following exercise. The incidence of ER in the study was 4% (3/77).
The results confirmed that oral administration of dantrolene sodium, 1 h before exercise, had a statistically significant effect on reducing the difference between pre- and post exercise plasma CK levels compared with a placebo in the same animals, and preventing clinical ER in susceptible individuals.
This study suggested that dantrolene sodium is of use in controlling ER in the Thoroughbred racehorse. Further investigation into pre- and post exercise myoplasmic calcium levels and the repeat of the study late in the season when horses receive a much higher energy ration and more strenuous exercise would appear to be warranted.
丹曲林钠(商品名:硝苯呋海因)已被广泛用于治疗人类肌病,有传闻证据表明,它对控制赛马运动性横纹肌溶解(ER)具有临床益处,尽管目前缺乏支持这一观点的数据。
在英国纽马克特进行一项随机、双盲、安慰剂对照的交叉试验,以研究口服丹曲林钠对控制ER的疗效,该试验涉及77匹纯种赛马。
马匹分两次接受治疗,每次间隔1周,治疗日与每次在厩舍休息2天后恢复运动的时间一致。第一次治疗时,每匹马被随机选择在运动前1小时口服800毫克丹曲林钠或颜色匹配的安慰剂。第二次治疗时交叉使用另一种治疗方法,每匹马因此作为自身对照。使用血清肌酸激酶(CK)水平升高来评估ER程度,用运动后6小时血样中测得的CK水平减去运动前血样中的CK水平。对于每匹马,计算安慰剂和丹曲林治疗之间运动前后CK值变化的差异,正值表明安慰剂组CK升高幅度大于丹曲林钠治疗组。
所有马匹的总体平均差异为+104.8国际单位/升,使用非参数威尔科克森符号秩检验拒绝了原假设,即安慰剂和丹曲林治疗之间运动后CK值非正态分布的升高没有真正差异(P = 0.0013)。此外,接受丹曲林钠治疗的马匹均未出现ER的临床症状,而3匹接受安慰剂治疗的马匹在运动后出现了ER。本研究中ER的发生率为4%(3/77)。
结果证实,与同一动物使用安慰剂相比,运动前1小时口服丹曲林钠对降低运动前后血浆CK水平的差异具有统计学显著效果,并可预防易感个体发生临床ER。
本研究表明丹曲林钠可用于控制纯种赛马的ER。进一步研究运动前后肌浆钙水平,并在赛季后期重复该研究,此时马匹摄入的能量更高且运动强度更大,似乎是有必要的。