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西地那非改善先天性特发性巨食管犬的临床体征和影像学特征:一项随机对照试验。

Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial.

作者信息

Quintavalla F, Menozzi A, Pozzoli C, Poli E, Donati P, Wyler D K, Serventi P, Bertini S

机构信息

Department of Veterinary Science, University of Parma, Parma, Italy.

Department of Neuroscience, University of Parma, Parma, Italy.

出版信息

Vet Rec. 2017 Apr 22;180(16):404. doi: 10.1136/vr.103832. Epub 2017 Feb 10.

DOI:10.1136/vr.103832
PMID:28188161
Abstract

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty-one puppies were randomly assigned to two groups (treatment and control). The dogs were given sildenafil oral suspension 1 mg/kg every 12 hours for 14 days or placebo in a masked fashion. Clinical signs (frequency of regurgitation and weight gain) and oesophagrams (relative oesophageal diameter, ROD) were evaluated in order to assess the efficacy of drug treatment, by examiners who were unaware of the study protocol. In addition, a set of in vitro experiments on isolated samples of canine lower oesophageal sphincter (LOS) was performed, and the effects of increasing concentrations of sildenafil on basal tone and electrically-stimulated motility were assessed. Sildenafil administration significantly reduced the number of regurgitation episodes (0.88±1.40 v 2.65±1.56, P<0.0001) and significantly increased weight gain in the treated dogs compared to controls (79.76±28.30 per cent v 53.40±19.30 per cent, P=0.034). ROD values, at the end of the treatment period, were significantly decreased in the sildenafil group, compared to pre-treatment values (0.97±0.19 v 0.24±0.14, P<0.0001), in contrast to control subjects (0.98±0.17 v 1.10±0.25, P=0.480). In accordance with the in vivo findings, sildenafil dose-dependently reduced basal tone and increased electrically-induced relaxation of dog LOS samples. These results suggest that sildenafil citrate helps ameliorate clinical and radiographic signs in dogs with CIM by reducing LOS tone, and could represent a novel therapeutic tool for the treatment of this disease.

摘要

我们评估了口服枸橼酸西地那非对患有先天性特发性巨食管(CIM)犬的疗效。21只幼犬被随机分为两组(治疗组和对照组)。以盲法给犬每12小时口服1mg/kg西地那非混悬液,持续14天或给予安慰剂。由不了解研究方案的检查人员评估临床症状(反流频率和体重增加情况)和食管造影(相对食管直径[ROD]),以评估药物治疗的疗效。此外,对犬下食管括约肌(LOS)的分离样本进行了一组体外实验,评估了西地那非浓度增加对基础张力和电刺激运动性的影响。与对照组相比,给予西地那非显著减少了反流发作次数(0.88±1.40对2.65±1.56,P<0.0001),并显著增加了治疗组犬的体重增加(79.76±28.30%对53.40±19.30%,P=0.034)。与治疗前值相比,治疗期结束时西地那非组的ROD值显著降低(0.97±0.19对0.24±0.14,P<0.0001),而对照组则相反(0.98±0.17对1.10±0.25,P=0.480)。与体内研究结果一致,西地那非剂量依赖性地降低了犬LOS样本的基础张力,并增加了电诱导的松弛。这些结果表明,枸橼酸西地那非通过降低LOS张力有助于改善CIM犬的临床和影像学症状,并可能成为治疗该疾病的一种新的治疗工具。

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