Lung Fluid Clearance in Chronic Heart Failure Patients

© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (May 2017) in accordance with the publisher’s archiving policyChronic elevation of pulmonary microvascular pressure (Pmv) consistently leads to alveolocapillary barrier thickening and reduction in the filtration coefficient. In animal models of chronic heart failure (CHF) the lung remains dry despite hydrostatic forces. As fluid flux is bi-directional, it has been postulated that an increase in alveolar fluid clearance may facilitate the dry lung when Pmv is chronically elevated. In this study we aimed to examine alveolar fluid clearance in ambulatory patients with CHF secondary to left ventricular (LV) systolic dysfunction compared against non-CHF controls. Lung clearance following aerosol delivery of 99mtechnetium (Tc)-diethyl triaminepentaacetic acid (DTPA) was measured non-invasively by scintigraphy and half time of 99mTc-DTPA clearance (T (1/2)) was calculated by mono-exponential curve fit. Alveolar fluid clearance measured as half time DTPA clearance was significantly faster in CHF patients than controls (P = 0.001). This was further defined by NYHA classification. No correlation was found between DTPA clearance and plasma epinephrine, norepinephrine or aldosterone hormone (P > 0.05). Our results support an association between increasing alveolar fluid clearance and disease severity in CHF, and the concept of controlled bi-directional fluid flux in CHF associated with increasing Pmv, and represents another defence mechanism of the lung against pulmonary oedema

Chronic elevation of pulmonary microvascular pressure in chronic heart failure reduces bi-directional pulmonary fluid flux

Aims. Chronic heart failure leads to pulmonary vascular remodelling and thickening of the alveolar–capillary barrier. We examined whether this protective effect may slow resolution of pulmonary oedema consistent with decreased bi-directional fluid flux. Methods and results. Seven weeks following left coronary artery ligation, we measured both fluid flux during an acute rise in left atrial pressure (n = 29) and intrinsic alveolar fluid clearance (n = 45) in the isolated rat lung. Chronic elevation of pulmonary microvascular pressure prevented pulmonary oedema and decreased lung compliance when left atrial pressure was raised to 20 cmH2O, and was associated with reduced expression of endothelial aquaporin 1 (P = 0.03). However, no other changes were found in mediators of fluid flux or cellular fluid channels. In isolated rat lungs, chronic LV dysfunction (LV end-diastolic pressure and infarct circumference) was also inversely related to alveolar fluid clearance (P ≤ 0.001). The rate of pulmonary oedema reabsorption was estimated by plasma volume expansion in eight patients with a previous clinical history of chronic heart failure and eight without, who presented with acute pulmonary oedema. Plasma volume expansion was reduced at 24 h in those with chronic heart failure (P = 0.03). Conclusions. Chronic elevation of pulmonary microvascular pressure in CHF leads to decreased intrinsic bi-directional fluid flux at the alveolar–capillary barrier. This adaptive response defends against alveolar flooding, but may delay resolution of alveolar oedema.A National Health and Medical Research Council (NHMRC) grant (#375129); Australian and New Zealand College of Anaesthetists (ANZCA) grant (#08/020); the Flinders Medical Centre Foundation