Use of a mixed endothelin receptor antagonist in portopulmonary hypertension:: A safe and effective therapy?
Use of a mixed endothelin receptor antagonist in portopulmonary hypertension:: A safe and effective therapy?
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DOI：
10.1053/j.gastro.2004.09.005
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发表时间：
2005-01-01
期刊：
影响因子：
29.4
通讯作者：
Gerbes, AL
中科院分区：
文献类型：
--
作者：
Kuntzen, C;Gülberg, V;Gerbes, AL
背景与目的：门脉肺动脉高压（PPHTN）是肝移植评估患者中3%-6%的严重并发症。内皮素-1是一种有效的血管收缩剂，可能在原发性肺动脉高压的发病机制中发挥作用，在最近的两项试验中，双重内皮素受体拮抗剂波生坦已显示出对该病的有益作用。内皮素在肺动脉高压和肝硬化发展中的作用已被提出。因此，我们假设内皮素受体阻断可能对PPHTN的治疗有益。方法：我们报告一例42岁的PPHTN合并酒精性肝硬化患者使用混合内皮素受体拮抗剂波生坦治疗。结果：患者从NYHA IV期迅速改善到II期，6个月内6分钟步行距离从0到590 m显著改善，治疗7个月后恢复全职锁匠工作。心血管参数的改善包括肺血管阻力降低60%，9个月时平均肺动脉压（mPAP）从55降至44毫米汞柱，1年后血浆b型利钠肽（BNP）从339 pg/mL降至19 pg/mL。除了短暂的全身血压下降外，没有其他不良事件。结论：据我们所知，这是第一个用内皮素受体拮抗剂治疗PPHTN患者的报告。这种显著和持续的改善为波生坦治疗PPHTN的安全性和有效性的对照研究提供了支持。
Background& Aims: Portopulmonary hypertension (PPHTN), a severe complication of portal hypertension is observed in 3%-6% of patients evaluated for liver transplantation. Enclothelin-1, a potent vasoconstrictor, is likely to play a role in the pathogenesis of primary pulmonary hypertension, and, in 2 recent trials, the dual endothelin receptor antagonist bosentan has shown beneficial effects in this disease. A role for endothelins in the development of both pulmonary hypertension and cirrhosis has been suggested. We therefore hypothesized that endothelin receptor blockade may be beneficial in the treatment of PPHTN. Methods: We report a case of a 42-year-old patient with PPHTN and alcoholic cirrhosis treated with the mixed endothelin receptor antagonist bosentan. Results: The patient rapidly improved from NYHA IV to stage II, experienced a remarkable improvement of 6-minute walking distance from 0 to 590 m within 6 months, and resumed working full-time as a locksmith after 7 months of treatment. Improvement of cardiovascular parameters included a reduction of pulmonary vascular resistance by 60%, a decrease of mean pulmonary artery pressure (mPAP) from 55 to 44 mm Hg at 9 months, and a decline of plasma B-type natriuretic peptide (BNP) from 339 pg,/mL to :19 pg/mL after :1 year. There were no adverse events except for a transient decrease in systemic blood pressure. Conclusions: To our knowledge, this is the first report of a patient with PPHTN treated with an endothelin receptor antagonist. The marked and sustained improvement supports the undertaking of controlled studies of the safety and efficacy of bosentan in PPHTN.