Sildenafil and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.
Sildenafil and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.
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西地那非和新生仔猪慢性缺氧引起的肺动脉高压的早期阶段。
DOI：
10.1002/ppul.20229
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发表时间：
2005
影响因子：
3.1
通讯作者：
Fike,CandiceD
中科院分区：
文献类型：
--
作者：
Binns-Loveman,KarenM;Kaplowitz,MarkR;Fike,CandiceD
设计可能预防新生儿肺动脉高压发作或进展的治疗方法很少受到关注。我们的主要目的是确定西地那非（一种选择性磷酸二酯酶抑制剂）是否可预防新生猪慢性缺氧诱导的肺动脉高压的早期发展。另一个目的是确定西地那非是否会导致慢性肺动脉高压小猪的肺血管扩张而不引起全身血管扩张。将仔猪在室内空气（对照，n = 5）或10- 11%O2（缺氧，n = 17）中饲养3天。一些仔猪（n = 4）在整个缺氧暴露期间接受了12 mg/kg/天的经口西地那非给药。所有仔猪均麻醉并插管，测量肺动脉压（Ppa）、肺楔压（Pw）、主动脉压（Ao）和心输出量（CO）。然后，对于在缺氧中饲养3天的一些仔猪，给予单次口服西地那非剂量（3 mg/kg，n = 6）或安慰剂（n = 5），并重复血流动力学测量。对于在缺氧条件下饲养3天的仔猪，平均Ppa和计算的PVR均高于对照仔猪的相应值。在整个低氧暴露期间接受西地那非的仔猪与未接受西地那非的仔猪之间，平均Ppa和PVR无差异。对于慢性缺氧诱导的肺动脉高压仔猪，接受单次口服西地那非给药后，平均Ppa和PVR降低，而平均Pw、CO、平均Ao和全身血管阻力保持不变。安慰剂给药后，所有血流动力学测量值均无变化。口服西地那非不影响新生仔猪慢性缺氧诱导的肺动脉高压的早期阶段。然而，在慢性缺氧诱导的肺动脉高压仔猪中，单次经口给予西地那非可引起肺血管舒张，而无全身血管舒张，这可能具有治疗意义。© 2005 Wiley利斯公司
Devising therapies that might prevent the onset or progression of pulmonary hypertension in newborns has received little attention. Our major objective was to determine whether sildenafil, a selective phosphodiesterase inhibitor, prevents the development of an early stage of chronic hypoxia‐induced pulmonary hypertension in newborn pigs. Another objective was to determine whether sildenafil causes pulmonary vasodilation without systemic vasodilation in piglets with chronic pulmonary hypertension. Piglets were raised in room air (control, n = 5) or 10–11% O2(hypoxic, n = 17) for 3 days. Some piglets (n = 4) received oral sildenafil, 12 mg/kg/day, throughout exposure to hypoxia. All piglets were anesthetized and catheterized, and pulmonary arterial pressure (Ppa), pulmonary wedge pressure (Pw), aortic pressure (Ao), and cardiac output (CO) were measured. Then for some piglets raised in hypoxia for 3 days, a single oral sildenafil dose (3 mg/kg, n = 6) or placebo (n = 5) was given, and hemodynamic measurements were repeated. For piglets raised in hypoxia for 3 days, mean Ppa and calculated PVR were elevated above respective values in control piglets. Mean Ppa and PVR did not differ between piglets that received sildenafil throughout exposure to hypoxia and those that did not. For piglets with chronic hypoxia‐induced pulmonary hypertension that received a single oral dose of sildenafil, mean Ppa and PVR decreased, while mean Pw, CO, mean Ao, and systemic vascular resistance remained the same. All hemodynamic measurements were unchanged after placebo. Oral sildenafil did not influence the early stage of chronic hypoxia‐induced pulmonary hypertension in newborn piglets. However, a single oral dose of sildenafil caused pulmonary vasodilation, without systemic vasodilation, in piglets with chronic hypoxia‐induced pulmonary hypertension, which may have therapeutic implications. © 2005 Wiley‐Liss, Inc.