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Alveolar-Capillary Membrane Dysfunction in Heart Failure^*

Evidence of a Pathophysiologic Role

^* From the Department of Medicine and Surgery, University of Milano, Cardiopulmonary Laboratory, Cardiology Division, San Paolo Hospital, Milano, Italy.

Correspondence to: Marco Guazzi, MD, PhD, Department of Medicine and Surgery, University of Milano, Cardiopulmonary Laboratory, Cardiology Division, San Paolo Hospital, Via A. di Rudini, 8, 20142 Milano, Italy; e-mail: Marco.Guazzi{at}unimi.it

Chronic heart failure (CHF) increases the resistance to gas transfer across the alveolar-capillary interface. Recent reports highlight the pathophysiologic relevance of changes in the lung leading to impaired fluid and gas exchange in the distal airway spaces. Under experimental conditions, an acute pressure or volume overload can injure the alveolar blood-gas barrier. This may disrupt its anatomic configuration, cause the loss of regulation of fluid-flux, and thereby affect alveolar gas conductance properties. These ultrastructural changes have been identified under the term of stress failure of the alveolar-capillary membrane. In the short term, these alterations are reversible due to the reparative properties of the alveolar surface. However, when the alveolar-capillary membrane is chronically challenged, for instance in patients with CHF, by noxious stimuli, such as humoral, cytotoxic, and genetic factors other than by mechanical trauma, remodeling of pathophysiologic and clinical importance may take place. These changes in some respects resemble the remodeling process in the heart. Emerging findings support the view that, in patients with CHF, alveolar-capillary membrane dysfunction may contribute to symptom exacerbation and exercise intolerance, and may be an independent prognosticator of clinical course. Angiotensin-converting enzyme inhibitors ameliorate the alveolar membrane gas conductance abnormality, reflecting improvement in the remodeling process. This article reviews the putative mechanisms involved in the impairment in gas diffusion in CHF patients and provides a link between physiologic changes and clinical findings.

Key Words: alveolar gas diffusion • exercise • heart failure

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