RELATIONSHIP BETWEEN KIDNEY-FUNCTION, HEMODYNAMIC VARIABLES AND CIRCULATING BIG ENDOTHELIN LEVELS IN PATIENTS WITH SEVERE REFRACTORY HEART-FAILURE

Fluid retention is a major characteristic of symptomatic, progressive heart failure when a main factor implicated in the pathogenesis of ren al dysfunction is renal hypoperfusion. This may be a consequence of fo rward cardiac failure, resulting in a low cardiac output integrating p oor left ventricular function secondary to myocardial impairment and i ncreased resistance in the regional renal vasculature secondary to loc ally released vasoconstrictors, e. g. endothelin. So far, the role of the pulmonary circulation in perpetuating renal dysfunction in heart f ailure is unclear. Methods. We investigated the relationship of hemody namic 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 II I-IV, based on idiopathic causes in 8 and ischemic causes in 10 patien ts. Renal plasma flow (RPF) was established by paraaminohippurate (PAH ) clearance and the glomerular filtration rate (GFR) was measured by i othalamate clearance. Results. Plasma big endothelin (ET) levels were increased above the upper normal range (1.8 fmol/ml) in 16 out of 18 p atients, averaging 5.0 +/- 0.8 fmol/ml (1.7-11.9 fmol/ml). Positive co rrelations to big Ei plasma levels were detected with mean pulmonary p ressure (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 ten dency 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 pres sure (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 vent ricular ejection fraction (r = 0.49, p < 0.05). Conclusion. The findin gs 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 - b y pulmonary vasoconstriction - play a part in the increased pulmonary filling pressures.