title: Chronic elevation of pulmonary microvascular pressure in chronic heart failure reduces bi-directional pulmonary fluid flux.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Intensive and Critical Care Unit, Flinders Medical Centre, and Department of Critical Care Medicine, Flinders University, Adelaide, Australia. dani.dixon@flinders.edu.au
authors.forename: Dani-Louise
authors.initials: DL
authors.lastname: Dixon
authors.forename: George C
authors.initials: GC
authors.lastname: Mayne
authors.forename: Kim M
authors.initials: KM
authors.lastname: Griggs
authors.forename: Carmine G
authors.initials: CG
authors.lastname: De Pasquale
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bersten
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D002196:Capillaries / Q000503:physiopathology; D002908:Chronic Disease; D015633:Extravascular Lung Water / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010953:Plasma Volume / Q000502:physiology; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D011654:Pulmonary Edema / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C496022:Aqp1 protein, rat; D051398:Aquaporin 1