Bradykinin production and increased pulmonary endothelial permeability during acute respiratory failure in unanesthetized sheep.
Bradykinin production and increased pulmonary endothelial permeability during acute respiratory failure in unanesthetized sheep.
复制标题
未麻醉绵羊急性呼吸衰竭期间缓激肽的产生和肺内皮通透性增加。
DOI：
10.1172/jci110061
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Mellins,RB
中科院分区：
文献类型：
--
作者：
O'Brodovich,HM;Stalcup,SA;Pang,LM;Lipset,JS;Mellins,RB
为了研究呼吸衰竭时肺水肿的机制，我们研究了有血管导管、胸膜气囊和慢性肺淋巴瘘的未麻醉绵羊。每15分钟测定血气、血压、心输出量、淋巴流量(Qlym)、血浆和淋巴白蛋白(molwt，70,000)、免疫球蛋白(igg，molwt，150,000)、IgM(molwt，900,000)和血液中缓激肽浓度。两组患者的心输出量和肺动脉压均增加，而左房压无变化。单独酸中毒(动脉pH=7.16，PaCO_2=81 mm Hg，PaO_2=250 mm Hg)导致淋巴流量增加一倍，蛋白流量略有增加，淋巴与血浆蛋白浓度(L/P)比值降低。酸中毒-低氧动物(动脉pH=7.16，PaCO_2=84 mm Hg，PaO_2=48 mm Hg)使Qlym增加两倍。在这些动物中，白蛋白、免疫球蛋白和免疫球蛋白M淋巴流量的增加显著(P<；0.05)大于酸中毒单独组或左房压力升高的动物(n=5；P<；0.05)。此外，大蛋白(IgM)通量增加的百分比大于小蛋白(白蛋白)通量的百分比(P<；0.05)。单纯酸中毒时，仅肺动脉缓激肽浓度升高(1.27±0.25 ng/mlSE)，而酸中毒合并缺氧时，肺动脉缓激肽浓度(4.83±1.14 ng/ml)和主动脉缓激肽浓度(2.74±0.78 ng/ml)均升高。这些研究表明，高碳酸血症会刺激体内缓激肽的产生。叠加低氧，从而减少缓激肽的降解，与Qlym的持续上升和肺对蛋白质的通透性增加相关。
To investigate mechanisms of pulmonary edema in respiratory failure, we studied unanesthetized sheep with vascular catheters, pleural balloons, and chronic lung lymph fistulas. Animals breathed either a hypercapnic-enriched oxygen (n= 5) or a hypercapnic-hypoxic (n= 5) gas mixture for 2 h. Every 15 min blood gases, pressures, cardiac output, lymph flow (Qlym), plasma and lymph albumin (mol wt, 70,000), IgG (mol wt, 150,000), IgM (mol wt, 900,000), and blood bradykinin concentrations were determined. In both groups, cardiac output and pulmonary arterial pressures increased, whereas left atrial pressures were unchanged. Acidosis alone (arterial pH = 7.16, PaCO2= 81 mm Hg, PaO2= 250 mm Hg) resulted in a doubling of lymph flow, a small increase in protein flux, and a decrease in lymph to plasma protein concentration (L/P) ratio for all three proteins. Acidotic-hypoxic animals (arterial pH = 7.16, PaCO2= 84 mm Hg, PaO2= 48 mm Hg) tripled Qlym. In these animals the increase in lymphatic flux of albumin, IgG, and IgM was significantly (P< 0.05) greater than that seen in either the acidosis alone group or in animals where left atrial pressures were elevated (n= 5;P< 0.05). Also, their percent increase in flux of the large protein (IgM) was greater than for the small protein (albumin) (P< 0.05). With acidosis alone, only pulmonary arterial bradykinin concentration increased (1.27±0.25 ng/ml SE), whereas acidosis plus hypoxia elevated both pulmonary arterial bradykinin concentrations (4.83±1.14 ng/ml) and aortic bradykinin concentration (2.74±0.78 ng/ml). These studies demonstrate that hypercapnic acidosis stimulates in vivo production of bradykinin. With superimposed hypoxia, and therefore decreased bradykinin degradation, there is an associated sustained rise in Qlym with increased lung permeability to proteins.