摘要目的 研究内皮素受体拮抗剂波生坦对Fontan术后患者中远期预后的影响.方法 39例行Fontan手术的患者按照住院号单双号随机分为内皮素受体拮抗剂波生坦组(波生坦组,16例)和对照组(23例).波生坦组于Fontan术后7d内开始口服波生坦,体质量≤10 kg的患者第1个月每次7.8125 mg,每日2次;体质量10～20 kg的患者第1个月每次15.625 mg,每日2次;体质量20 ～30 kg的患者第1个月每次31.25 mg,每日2次;体质量＞30 kg的患者第1个月每次62.5 mg,每日2次.所有患者均于第2个月开始增加波生坦剂量至前1个月的2倍,服药时间＞1年.对照组不服用肺动脉高压靶向药物治疗和(或)影响肺动脉压力的药物.随访2年后对比两组患者的病死率、失蛋白肠病发生率、肺动静脉瘘发生率、6 min步行距离及心功能指标等.结果 随访2年,对照组病死率高于波生坦组,但差异无统计学意义.波生坦组患者失蛋白肠病及术后新出现肺动静脉瘘的发生率显均著低于对照组[分别为6.25％比34.78％(P=0.01)和6.25％比39.13％ (P =0.02)].波生坦组患者(年龄≥3岁)6 min步行距离为(485±44)m,显著优于对照组的(302 ±183) m(P=0.02).波生坦组纽约心功能分级Ⅲ或Ⅳ级的患者少于对照组(3例比14例,P=0.01).波生坦组患者血管活性因子B型利钠肽、内皮素、血栓素水平分别为279.07±128.17、3.30±0.61和97.2±24.0,均显著低于对照组的457.67±221.30、4.98±1.24和163.22±24.40(P均＜0.05).两组患者前列环素的水平比较差异无统计学意义.两组患者心律失常发生率差异无统计学意义.两组均未出现血栓事件.结论 Fontan术后规律服用内皮素受体拮抗剂可有效改善患者预后、降低并发症发生率和病死率.

abstractsObjective To investigate the long-term effect of bosentan on outcome in patients after Fontan operation.Methods Patients after Fontan surgery were randomly divided into bosentan group (B,n =16) and control group (C,n =23).Bosentan was applied within 7 days after Fontan surgery as follows:at the first month,7.8125 mg Bid for patients with body weight≤10 kg; 15.625 mg Bid for patients with body weight between 10-20 kg; 31.25 mg Bid for patients with body weight 20-30 kg and 62.5 mg Bid for patients with body weight ＞ 30 kg.At the second month,the bosentan dose was doubled and Bosentan therapy was continued for more than 1 year.Group C didn't take drugs affecting pulmonary artery pressure.All patients were followed up for 2 years and incidence of mortality,protein losing enteropathy,pulmonary arteriovenous fistulae,6-minute walk test,heart function were compared between the two groups.Results After 2 years,mortality tended to be lower in group B compared to group C [6.25％ (1/16) vs.21.8％ (5/23),P ＞ 0.05].Incidence of pulmonary arteriovenous fistulae and protein losing enteropathy were significantly lower in group B than in group C(6.25％ vs.34.78％,P =0.01 ;6.25％ vs.39.13％,P =0.02,respectively).The results of 6-minute walk test[(485 ± 44) m vs.(302 ± 183) m] and heart function in group B (3 NYHA Ⅲ/Ⅳ patients in group B vs.14 NYHA Ⅲ/Ⅳ patients in group C,all P＜0.05) were all better than group C.The concentrations of vasoactive factors such as brain natriuretic peptide (BNP,279.07 ± 128.17 vs.457.67 ± 221.30),endothelin (ET,3.30 ± 0.61 vs.4.98 ± 1.24) and thromboxane (TXA2,97.2 ± 24.0 vs.163.22 ± 24.4) were also significantly lower in group B than in group C (all P ＜ 0.05).Prostacyclin (PGI2) level and incidence of arrhythmias were similar between the two groups.There was no thrombotic event in both groups during follow up.Conclusion Bosentan trerapy in patients post Fontan operation could reduce the incidence of pulmonary arteriovenous fistulae and protein losing enteropathy and improve heart function.