Alveolar gas diffusion abnormalities in heart failure

J Card Fail. 2008 Oct;14(8):695-702. doi: 10.1016/j.cardfail.2008.06.004. Epub 2008 Jul 18.


In heart failure (HF), development of pressure or volume overload of the lung microcirculation elicits a series of structural adaptations, whose functional correlate is an increased resistance to gas transfer across the alveolar-capillary membrane. Acutely, hydrostatic mechanical injury causes endothelial and alveolar cell breaks, impairment of the cellular pathways involved in fluid filtration and reabsorption, and resistance to gas transfer. This process, which is reminiscent of the so-called alveolar-capillary stress failure, is generally reversible. When the alveolar membrane is chronically challenged, tissue alterations are sustained and a typical remodeling process may take place that is characterized by fixed extracellular matrix collagen proliferation and reexpression of fetal genes. Remodeling leads to a persistent reduction in alveolar-capillary membrane conductance and lung diffusion capacity. Changes in gas transfer not only reflect the underlying lung tissue damage but also bring independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities. They are not responsive to fluid withdrawal by ultrafiltration and tend to be refractory even to heart transplantation. Some drugs can be effective that modulate lung remodeling (eg, angiotensin-converting enzyme inhibitors, whose impact on the natural course of cardiac remodeling is well known) or that increase nitric oxide availability and nitric oxide-mediated pulmonary vasodilation (eg, type 5 phosphodiesterase inhibitors). This review focuses on the current knowledge of these topics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Capillary Permeability*
  • Disease Progression
  • Exercise Tolerance
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology*
  • Heart Failure / therapy
  • Humans
  • Prognosis
  • Pulmonary Diffusing Capacity*
  • Pulmonary Gas Exchange
  • Respiratory Function Tests