Liska J, Holm P, Owall A, Franco-Cereceda A
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Acta Physiol Scand. 1995 Aug;154(4):489-98. doi: 10.1111/j.1748-1716.1995.tb09934.x.
Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pulmonary circulation after hypoxia-induced hypertension. Pits under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled O2 from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion through the Swan-Ganz catheter in the right ventricle. Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET-1 (10, 25 and 50 ng kg-1 min-1) dose-dependently decreased MPAP and PVR; at a higher dose (100 ng kg-1 min-1), the PVR returned to the level observed at hypoxia. ET-infusions at 50 and 100 ng kg-1 min-1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET-1 infusion. Infusion of ET-3 evoked effects similar to those of ET-1 infusions, although the response to ET-3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET-1 (25 ng kg-1 min-1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET-infusion. ET-1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia. It is concluded that in the pig, short-term ET-infusion reduces the pulmonary hypertension associated with acute hypoxia.
先前的研究表明，在肺血管阻力增加的病理生理状态下，强效血管活性肽内皮素（ET）的血浆水平会升高，并且据推测ET可能在缺氧性肺动脉高压中起一定作用。因此，我们评估了缺氧诱导高血压后ET输注对猪肺循环的影响。在全身麻醉下，猪通过气管内导管进行人工通气，通过将吸入氧气分数从0.21降至0.10来诱导缺氧。使用Swan-Ganz导管结合热稀释法连续记录血流动力学参数以测量心输出量。通过右心室的Swan-Ganz导管静脉输注ET-1或ET-3。缺氧导致肺血管阻力（PVR）、平均肺动脉压（MPAP）和右心室搏功（RVSW）可重复增加，而全身血管阻力（SVR）略有下降。ET-1（10、25和50 ng·kg⁻¹·min⁻¹）的累积输注剂量依赖性地降低了MPAP和PVR；在较高剂量（100 ng·kg⁻¹·min⁻¹）时，PVR恢复到缺氧时观察到的水平。50和100 ng·kg⁻¹·min⁻¹的ET输注引起SVR增加，心输出量（CO）和每搏量（SV）减少。在ET-1输注期间，RVSW也逐渐降低。ET-3的输注引起的效应与ET-1输注相似，尽管对ET-3的反应起效没有那么快。在第二组动物中，重复进行15分钟的缺氧期会引起稳定、可重复的反应，PVR、MPAP和RVSW持续增加，在常氧期间恢复到基线值。输注ET-1（25 ng·kg⁻¹·min⁻¹）引起PVR和MPAP迅速下降，在停止ET输注后迅速恢复正常。在此浓度下输注ET-1本身在常氧期间不影响血流动力学参数。结论是，在猪中，短期输注ET可降低与急性缺氧相关的肺动脉高压。
