Kos T, Pacher R, Wimmer A, Bojic A, Hülsmann M, Frey B, Mayer G, Yilmaz N, Skvarilova L, Spinar J, Vitovec J, Toman J, Woloszcuk W, Stanek B
Department of Cardiology and Nephrology, University of Vienna, Austria.
Wien Klin Wochenschr. 1998 Feb 13;110(3):89-95.
Fluid retention is a major characteristic of symptomatic, progressive heart failure when a main factor implicated in the pathogenesis of renal dysfunction is renal hypoperfusion. This may be a consequence of forward cardiac failure, resulting in a low cardiac output integrating poor left ventricular function secondary to myocardial impairment and increased resistance in the regional renal vasculature secondary to locally released vasoconstrictors, e.g. endothelin. So far, the role of the pulmonary circulation in perpetuating renal dysfunction in heart failure is unclear.
We investigated the relationship of hemodynamic variables obtained during right heart catheterization and plasma big endothelin levels to renal function variables in 18 male patients aged 52 +/- 3 years, with heart failure in the NYHA function class III-IV, based on idiopathic causes in 8 and ischemic causes in 10 patients. Renal plasma flow (RPF) was established by paraaminohippurate (PAH) clearance and the glomerular filtration rate (GFR) was measured by iothalamate clearance.
Plasma big endothelin (ET) levels were increased above the upper normal range (1.8 fmol/ml) in 16 out of 18 patients, averaging 5.0 +/- 0.8 fmol/ml (1.7-11.9 fmol/ml). Positive correlations to big ET plasma levels were detected with mean pulmonary pressure (r = 0.73, p < 0.001) pulmonary capillary wedge pressure (r = 0.56, p < 0.05) and pulmonary vascular resistance index (r = 0.69, p < 0.01). Glomerular filtration rate (70 +/- 7 ml/min) and renal plasma flow (358 +/- 36 ml/min) were considerably reduced and exhibited a tendency to correlate inversely with big ET levels (r = -0.46, p = 0.056 and r = -0.44, p = 0.069, respectively). Contrary to expectations, RPF did not correlate significantly with cardiac index, systemic vascular resistance index or arterial blood pressure. In contrast, significant correlations were detected of RPF with pulmonary capillary wedge pressure (r = -0.69, p < 0.01), mean pulmonary artery pressure (r = -0.65, p < 0.01), right atrial pressure (r = -0.47, p < 0.05) and right ventricular ejection fraction (r = 0.49, p < 0.05).
The findings suggest a role for endothelin in renal vasoconstriction and accord well with the concept that in severe heart failure renal hypoperfusion--by volume retention--as well as increased endothelin synthesis--by pulmonary vasoconstriction--play a part in the increased pulmonary filling pressures.
液体潴留是有症状的进行性心力衰竭的主要特征，而肾功能不全发病机制中的一个主要因素是肾灌注不足。这可能是前向性心力衰竭的结果，导致心输出量降低，这是由于心肌损伤继发左心室功能不良以及局部释放的血管收缩剂（如内皮素）导致肾局部血管系统阻力增加所致。到目前为止，肺循环在心力衰竭中使肾功能不全持续存在的作用尚不清楚。
我们研究了18名年龄在52±3岁的男性患者在右心导管检查期间获得的血流动力学变量和血浆大内皮素水平与肾功能变量之间的关系，这些患者为纽约心脏协会（NYHA）功能分级III-IV级心力衰竭患者，其中8例为特发性病因，10例为缺血性病因。通过对氨基马尿酸（PAH）清除率确定肾血浆流量（RPF），并通过碘他拉酸盐清除率测量肾小球滤过率（GFR）。
18例患者中有16例血浆大内皮素（ET）水平高于正常上限（1.8 fmol/ml），平均为5.0±0.8 fmol/ml（1.7 - 11.9 fmol/ml）。发现平均肺动脉压（r = 0.73，p < 0.001）、肺毛细血管楔压（r = 0.56，p < 0.05）和肺血管阻力指数（r = 0.69，p < 0.01）与大内皮素血浆水平呈正相关。肾小球滤过率（70±7 ml/min）和肾血浆流量（358±36 ml/min）显著降低，并呈现出与大内皮素水平呈负相关的趋势（分别为r = -0.46，p = 0.056和r = -0.44，p = 0.069）。与预期相反，肾血浆流量与心脏指数、全身血管阻力指数或动脉血压无显著相关性。相反，发现肾血浆流量与肺毛细血管楔压（r = -0.69，p < 0.01）、平均肺动脉压（r = -0.65，p < 0.01）、右心房压（r = -0.47，p < 0.05）和右心室射血分数（r = 0.49，p < 0.05）有显著相关性。
这些发现表明内皮素在肾血管收缩中起作用，并且与以下概念相符，即在严重心力衰竭中，肾灌注不足（通过液体潴留）以及内皮素合成增加（通过肺血管收缩）在肺充盈压升高方面起作用。
