948-52 Paradoxical Neurohumoral Axis Inhibition After Body Fluid Volume Depletion in Patients with Congestive Heart Failure and Water Retention

Abstract

Hypovolemia stimulates the sympathoadrenal and renin systems and water retention. In congestive heart failure (CHF) reduction of cardiac output (CO) and, to the extent that it occurs, decrease of blood pressure (BP), have been suggested to be perceived as a state of underfilling of the arterial compartment, and to promote and perpetuate neurohumoral activation and retention of fluid. This study was aimed to probe whether intravascular volume deficit accounts for patterns that largely exceed the limits of a homeostatic response, as sometimes observed in more advanced stages of the syndrome. We reduced the body fluid mass with a non-pharmacological method, ultrafiltration (UF), in patients with CHF and water retention, and monitored the neurohumoral reaction. In 22 patients, UF was performed with a diafilter, which was part of an external venous circuit, whose flow was regulated to produce 500 ml/hour of ultrafiltrate (average total amount = 3122 ± 1199 ml) until right atrial pressure was lowered to 50% of baseline. Hemodynamics, plasma renin activity (PRA), norepinephrine (NE) and aldosterone (AL) were evaluated before and in the 48 hours after UF. Soon after the procedure, associated with a 20% reduction of plasma volume (PV) and a moderate decrease of CO and BP (consistent with a diminished degree of filling of the arterial compartment), there was an obvious fall of NE, PRA and AL. In the next 48 hours we recorded a) recovery of PV. CO and BP, b) increasing depression of the neurohumoral axis, c) striking enhancement of water and sodium excretion and resolution of peripheral edema and organ congestion. Changes of NE, PRA or AL were not related to changes of PV. CO and BP (variations in the state of arterial filling) and significantly correlated with the increase of urinary output and sodium excretion. Arterial underlilling, as a the main mechanism for activation of the neurohumoral axis and retention of fluid, does not apply to the more advanced stages of CHF. The parallelism observed between fall of circulating hormones and reabsorption of extravascular fluid suggests that hypoperfusion and/or congestion of organ, like kidney and lung, may reduce the clearance of circulating norepinephrine and contribute to keep renin and aldosterone raised. A positive feedback loop between fluid retention and plasma hormone levels appears to be a mechanism of progression of the syndrome.