Almeida John A, Riordan Stephen M, Liu Jia, Galhenage Sumedha, Kim Robert, Bihari David, Wegner Eva A, Cranney Gregory B, Thomas Paul S
Gastrointestinal and Liver Unit, The Prince of Wales Hospital and University of New South Wales, Sydney, Australia.
Eur J Gastroenterol Hepatol. 2007 Apr;19(4):341-6. doi: 10.1097/MEG.0b013e328014a3bf.
On the basis of limited experimental and clinical studies, increased activity of the vasodilatory nitric oxide-cyclic guanosine monophosphate pathway is considered to play a key role in the pathogenesis of hepatopulmonary syndrome. We report a 46-year-old woman with Child-Pugh class C cirrhosis and progressive dyspnoea for 12 months. Investigations revealed elevated circulating concentrations of nitric oxide metabolites and exhaled nitric oxide levels, an hyperdynamic circulation with low systemic vascular resistance and mean arterial pressure, a large right to left intrapulmonary shunt fraction on radiolabelled macroaggregated albumin perfusion scanning, positive contrast-enhanced echocardiography, reduced diffusion capacity of carbon monoxide, hypoxaemia and orthodeoxyia, all in keeping with severe hepatopulmonary syndrome. Sequential inhibition of the nitric oxide-cyclic guanosine monophosphate pathway using curcumin (diferuloylmethane), terlipressin and methylene blue was associated with substantial improvements in vascular tone and the hyperdynamic circulation. No improvement, however, in the intrapulmonary shunt was demonstrated. Both hypoxaemia and orthodeoxia were substantially, reproducibly and reversibly worsened with all three treatments. Our findings argue against the contention that intrapulmonary shunting and impairment in arterial oxygenation in hepatopulmonary syndrome are necessarily the consequence of on-going, nitric oxide-cyclic guanosine monophosphate-mediated vasodilatation, at least in the chronic stage, and, given the possibility of substantial worsening of pulmonary oxygen exchange, suggest that inhibition of the nitric oxide-cyclic guanosine monophosphate pathway should be avoided in this setting.
基于有限的实验和临床研究，血管舒张性一氧化氮-环磷酸鸟苷途径活性增加被认为在肝肺综合征的发病机制中起关键作用。我们报告一名46岁患有Child-Pugh C级肝硬化且进行性呼吸困难12个月的女性。检查发现循环中一氧化氮代谢产物浓度升高、呼出一氧化氮水平升高、高动力循环伴低体循环血管阻力和平均动脉压、放射性标记的大颗粒聚合白蛋白灌注扫描显示有大量右向左肺内分流分数、对比增强超声心动图阳性、一氧化碳弥散能力降低、低氧血症和直立性脱氧，所有这些均符合严重肝肺综合征。使用姜黄素（双阿魏酰甲烷）、特利加压素和亚甲蓝对一氧化氮-环磷酸鸟苷途径进行序贯抑制与血管张力和高动力循环的显著改善相关。然而，但未显示肺内分流有改善。所有三种治疗均使低氧血症和直立性脱氧显著、可重复且可逆地恶化。我们的研究结果反对以下观点，即至少在慢性期，肝肺综合征中的肺内分流和动脉氧合受损必然是持续的一氧化氮-环磷酸鸟苷介导的血管舒张的结果，并且鉴于肺氧交换可能显著恶化，提示在这种情况下应避免抑制一氧化氮-环磷酸鸟苷途径。
