Review Article
Alveolar Gas Diffusion Abnormalities in Heart Failure

https://doi.org/10.1016/j.cardfail.2008.06.004Get rights and content

Abstract

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.

Section snippets

Alveolar-Capillary Membrane

To guarantee an optimal gas exchange, the alveolar-capillary unit needs to be thin, resistant, and “fluid-free.” Several important mechanisms preserve these physiologic properties. Figure 1 depicts the 3-layer configuration (epithelium, interstitial space, and endothelium) of the alveolar-capillary unit with cellular pathways involved in water and Na+ transport.

Acute LV failure promotes an increase in capillary pressure or volume that disrupts the anatomic configuration of the membrane and

Clinical Relevance of Gas Diffusion Abnormalities in Chronic Heart Failure

Measurement of lung diffusion capacity for carbon monoxide (DLCO) or nitric oxide (DLNO) is generally used in clinical practice to evaluate the effectiveness of diffusive O2 transport.27 As originally suggested by Roughton and Forster,28 for a given alveolar volume (VA) and hemoglobin concentration, gas diffusion depends on 2 resistances arranged in series according to the following equation:

1/DLCO = 1/DM + 1/θCO × Vc, where DM is the alveolar-capillary membrane conductance, θCO is the rate of CO

Interventions Improving Gas Diffusion in Chronic Heart Failure

In patients with HF who undergo heart transplantation, diffusion abnormalities may persist despite an improvement in hemodynamic status.53 A relationship has also been established between the time course of the disease and extent of gas transfer alterations.54 Thus, impaired DLCO in chronic disease may not fully depend on a reduction of the global perfusion of the lung but may be related to the persistence of structural changes of the membrane. The clinical significance of this may even be

Conclusions

The resistance to gas diffusion across the alveolar-capillary membrane is increased in HF. Disruption of the alveolar anatomic configuration and impairment of cellular pathways involved in the fluid–flux regulation and gas exchange efficiency (ie, “stress failure” of the alveolar-capillary membrane) are well characterized in different experimental models of lung capillary injury. Similar changes may distinguish acute HF in humans and may be reversible. In the chronic phase of HF, a reduced

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    This report was supported by the Monzino Foundation, Milano, Italy.

    No conflict of interest exists.

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