Bernardi M, Gulberg V, Colantoni A, Trevisani F, Gasbarrini A, Gerbes A L
Patologia Speciale Medica I, University of Bologna, Italy.
J Hepatol. 1996 Feb;24(2):161-8. doi: 10.1016/s0168-8278(96)80025-0.
BACKGROUND/AIMS: The postural change from upright to supine is a physiological maneuvre which increases central blood volume. This model was used to investigate the effects of changes in effective volemia on plasma endothelin-1 and -3 concentrations in cirrhosis.
Plasma endothelin concentrations, measured by radio-immunoassay, were determined in 20 patients with cirrhosis, 10 of whom has ascites, and nine healthy control subjects, in the upright posture and 30, 60 and 120 min after the assumption of the supine position.
In the upright posture, endothelin-1 was 8.9 +/- 0.4 pg/ml and endothelin-3 3.7 +/- 0.6 (mean +/- SEM) pg/ml in control subjects. Endothelin-1 was increased only in patients with ascites (12.7 +/- 1.4 pg/ml, p < 0.05; patients without ascites: 9.7 +/- 0.7 pg/ml), while endothelin-3 was elevated in both patients with and without ascites (8.0 +/- 1.5 pg/ml, p < 0.01; 5.9 +/- 0.5 pg/ml, p = 0.01, respectively). In the supine position, no significant changes in endothelin-1 or -3 occurred either in patients with ascites or in controls throughout the observation period, while a reduction in endothelin-3 was found in compensated patients after 30 and 60 min. In patients, we found negative correlations between endothelin-3, but not endothelin-1, and mean arterial pressure, both in upright (r = -0.59; p < 0.01) and supine (r = -0.56; p = 0.01) positions, atrial natriuretic factor (r = 0.50; p < 0.05) and plasma renin activity (r = 0.67; p = 0.001) in the supine position alone. In patients with ascites, endothelin-1 was inversely correlated with both glomerular filtration rate (upright: r = -0.62; p = 0.06; supine: r = -0.71, p < 0.05) and renal sodium excretion (upright: r = -0.82; p < 0.01; supine: r = -0.88; p < 0.001).
Plasma endothelin-1 and -3 were increased in cirrhosis with ascites, while, in pre-ascitic cirrhosis, only endothelin-3 was increased in the upright posture. Although increased endothelin-3 was associated with features suggesting a reduced effective volemia, it is likely that other mechanisms than hypovolemia were mainly responsible for high plasma endothelin levels. Increased endothelin production may play a role in circulatory and renal function abnormalities of advanced cirrhosis.
背景/目的：从直立位到仰卧位的体位变化是一种可增加中心血容量的生理操作。本模型用于研究有效血容量变化对肝硬化患者血浆内皮素-1和-3浓度的影响。
采用放射免疫分析法测定20例肝硬化患者（其中10例有腹水）和9名健康对照者在直立位以及仰卧位30、60和120分钟后的血浆内皮素浓度。
在直立位时，对照组内皮素-1为8.9±0.4 pg/ml，内皮素-3为3.7±0.6（均值±标准误）pg/ml。仅腹水患者的内皮素-1升高（12.7±1.4 pg/ml，p<0.05；无腹水患者：9.7±0.7 pg/ml），而有腹水和无腹水患者的内皮素-3均升高（分别为8.0±1.5 pg/ml，p<0.01；5.9±0.5 pg/ml，p = 0.01）。在仰卧位时，腹水患者和对照组在整个观察期内内皮素-1或-3均无显著变化，而在代偿期患者中，30和60分钟后内皮素-3有所降低。在患者中，我们发现内皮素-3（而非内皮素-1）与平均动脉压在直立位（r = -0.59；p<0.01）和仰卧位（r = -0.56；p = 0.01）均呈负相关，仅在仰卧位时与心房利钠因子（r = 0.50；p<0.05）和血浆肾素活性（r = 0.67；p = 0.001）呈负相关。在有腹水的患者中，内皮素-1与肾小球滤过率（直立位：r = -0.62；p = 0.06；仰卧位：r = -0.71，p<0.05）和肾钠排泄（直立位：r = -0.82；p<0.01；仰卧位：r = -0.88；p<0.001）均呈负相关。
肝硬化腹水患者血浆内皮素-1和-3升高，而在腹水前期肝硬化患者中，仅直立位时内皮素-3升高。尽管内皮素-3升高与提示有效血容量减少的特征相关，但血浆内皮素水平升高可能主要由血容量不足以外的其他机制所致。内皮素生成增加可能在晚期肝硬化的循环和肾功能异常中起作用。
