The hypothesis was tested that cardiovascular and neuroendocrine (norepinephrine, renin, and vasopressin) responses to central blood volume expansion are blunted in compensated heart failure (HF). Nine HF patients [New York Heart Association class II-III, ejection fraction = 0.28 +/- 0.02 (SE)] and 10 age-matched controls (ejection fraction = 0.68 +/- 0.03) underwent 30 min of thermoneutral (34.7 +/- 0.02 degrees C) water immersion (WI) to the xiphoid process. WI increased (P < 0.05) central venous pressure by 3.7 +/- 0.6 and 3.2 +/- 0.4 mmHg and stroke volume index by 12.2 +/- 2.1 and 7.2 +/- 2.1 ml. beat(-1). m(-2) in controls and HF patients, respectively. During WI, systemic vascular resistance decreased (P < 0.05) similarly by 365 +/- 66 and 582 +/- 227 dyn. s. cm(-5) in controls and HF patients, respectively. Forearm subcutaneous vascular resistance decreased by 19 +/- 7% (P < 0.05) in controls but did not change in HF patients. Heart rate decreased less during WI in HF patients, whereas release of norepinephrine, renin, and vasopressin was suppressed similarly in the two groups. We suggest that reflex control of forearm vascular beds and heart rate is blunted in compensated HF but that baroreflex-mediated systemic vasodilatation and neuroendocrine responses to central blood volume expansion are preserved.

To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits a natriuresis. In HF, WI suppressed ANG II and aldosterone (Aldo) concentrations, increased the release of atrial natriuretic peptide (ANP), and elicited a natriuresis (P < 0.05 for all) compared with seated control. Compared with control subjects (n = 9), ANG II, Aldo, and ANP concentrations were increased (P < 0.05) in HF, whereas absolute and fractional sodium excretion rates were attenuated [47 +/- 16 vs. 88 +/- 15 micromol/min and 0.42 +/- 0.18 vs. 0.68 +/- 0.12% (mean +/- SE), respectively, both P < 0.05]. When ANG II and Aldo concentrations were further suppressed (P < 0.05) during WI in HF (by sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P < 0.05) to the level of control subjects (108 +/- 34 micromol/min and 0.70 +/- 0.23%, respectively). Renal free water clearance increased during WI in control subjects but not in HF, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast, renal free water clearance is attenuated in response to volume expansion in compensated HF despite normalized plasma AVP concentrations.

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BACKGROUND-The increased plasma disappearance of albumin has previously been described in decompensated congestive heart failure (CHF); this disappearance normalized after diuretic treatment. Cardiac transplantation (HTX) and current medical treatment affect microvascular structure and function. We investigated the plasma disappearance of albumin and the impact of microvascular thickness and electrostatic properties in patients with compensated CHF and after HTX. METHODS AND RESULTS-The fraction of intravascular albumin that passes to the extravascular space per unit time, as determined from the plasma disappearance of intravenously injected (131)I-labeled albumin, was increased to 7.8+/-1.7% in 16 patients with CHF compared with 18 controls (6.5+/-1.9%, P<0.05); these levels normalized after HTX (5.8+/-2.6%, P<0.01, n=17). The change in ratio between (131)I-albumin and simultaneously injected negatively charged glycosylated (125)I-albumin (selectivity index, >1/hour in controls) was lower in patients with HTX (0.993+/-0. 022/hour) than in controls (1.008+/-0.019/hour; P<0.05), which indicated a relatively increased plasma disappearance of negatively charged albumin in HTX patients. Capillary basement membrane thickness was evaluated semiquantitatively from skin biopsies and showed no difference in the 3 groups (control, CHF, and HTX patients). However, in all 3 study groups, subjects with thicker capillary basement membranes had lower albumin escape rates (6.1+/-1. 8%, n=32, versus 7.6+/-2.6% in subjects without thickening of capillary basement membranes, n=19; P<0.05). CONCLUSIONS-The plasma disappearance of albumin increased in patients with compensated CHF and it normalized after HTX. The present normalized capillary basement thicknesses in patients with CHF and the direct association between this parameter and plasma albumin disappearance indicate that previous compensatory microvascular basement membrane growth results in restricted permeability. Microvascular electrostatic properties did not relate to plasma albumin disappearance.