Alveolar Gas Diffusion Abnormalities in Heart Failure

doi:10.1016/j.cardfail.2008.06.004

Journal of Cardiac Failure

Volume 14, Issue 8, October 2008, Pages 695-702

https://doi.org/10.1016/j.cardfail.2008.06.004 Get 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/D_M + 1/θCO × Vc, where D_M 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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Citation Excerpt :
The cellular pathways involved in the transition to a fibrotic LA chamber may have a common background with pathways involved in the microvasculature lung remodeling process (see later in this article) and have been identified in angiotensin II and transforming growth factor beta-1 as actually the most potent stimulators of collagen synthesis. When LAP is abnormally increased, 2 major vascular modifications occur39: the first is a stress failure of the capillaries and alveolar membrane, showing as a typical acute phenomenon induced by barotrauma injury of lung microvessels, which disrupts endothelial function and permeability and impairs the biological and functional properties of the alveolar unit (gas exchange and fluid filtration and reabsorption). Overt pulmonary edema is the significant clinical correlate of capillary stress failure.

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

: No conflict of interest exists.

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Review ArticleAlveolar Gas Diffusion Abnormalities in Heart Failure

Abstract

Section snippets

Alveolar-Capillary Membrane

Clinical Relevance of Gas Diffusion Abnormalities in Chronic Heart Failure

Interventions Improving Gas Diffusion in Chronic Heart Failure

Conclusions

Alveolar-capillary membrane dysfunction in heart failure. Evidence of a pathophysiological role

Chest

The pathogenesis of acute pulmonary edema associated with hypertension

N Engl J Med

Cellular responses to mechanical stress. Invited review: pulmonary-capillary stress failure

J Appl Physiol

Alveolar fluid reabsorption is impaired by increased left atrial pressure in rats

Am J Physiol

Pulmonary capillaries are more resistant to stress failure in dogs than in rabbits

J Appl Physiol

Morpho-functional analysis of lung tissue in mild interstitial edema

Am J Physiol

Pulmonary interstitial pressure and proteoglycans during development of pulmonary edema

Am J Physiol

Composition, biophysical properties and morphometry of plasma membranes in pulmonary interstitial edema

Am J Physiol

Prolonged alveolar capillary barrier damage after acute cardiogenic pulmonary edema

Crit Care

Evolving changes in lung interstitial fluid content after acute myocardial infarction: mechanisms and pathophysiological correlates

Am J Physiol Heart Circ Physiol

Impeded alveolar-capillary gas transfer with saline infusion in heart failure

Hypertension

Acute respiratory distress syndrome

Interactions between permeability and hydrostatic pressure in perfused dogs lungs

J Appl Physiol

Lung epithelial ion transport and fluid movement during perinatal period

Am J Physiol

Fluid absorption by rat lung in situ: pathways for sodium entry in the luminal membrane of alveolar epithelium

J Physiol

Salt and water transport across alveolar and distal airway epithelia in the adult lung

Am J Physiol

Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, physiological significance

Annu Rev Physiol

Evidence for active sodium transport across alveolar epithelium of isolated rat lung

J Appl Physiol

The human pulmonary circulation

Its form and function in health and disease

The lungs in heart disease

Augmentation of liquid clearance via adenovirus-mediated transfer of Na+-K+ATPase β1 subunit gene

J Clin Invest

Na, K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure

Circulation

Impairment of transalveolar fluid transport and lung Na+-K+ATPase function by hypoxia in rats

J Appl Physiol

Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure

J Appl Physiol

Pulmonary microvascular permeability: responses to high vascular pressure after induction of pacing induced heart failure in dogs

Circ Res

Electron microscopic studies on the alveolar-capillary barrier in patients with chronic pulmonary edema

Jpn Circ J

Standardization of the single-breath determination of carbon monoxide uptake in the lung

Eur Respir J

Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in human lung, with special reference to true diffusing capacity of blood in the lung capillary

J Appl Physiol

Exercise intolerance following heart transplantation: the role of pulmonary diffusing capacity impairment

Chest

Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance

Circulation

Ventilatory and diffusion capacity in potential heart transplant recipients

Chest

Reduced pulmonary microvascular permeability in severe chronic left heart failure

Am Heart J

Pulmonary diffusion capacity in left ventricular dysfunction

Chest

Pulmonary function abnormalities in chronic severe cardiomyopathy preceding cardiac transplantation

Am Rev Respir Dis

Pulmonary function after successful heart transplantation

Chest

Diffusing capacity decreases after heart transplantation

Chest

Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure

J Am Coll Cardiol

Exercise intolerance in patients with chronic heart failure: role of pulmonary diffusing limitation

Review Article
Alveolar Gas Diffusion Abnormalities in Heart Failure

Augmentation of liquid clearance via adenovirus-mediated transfer of Na⁺-K⁺ATPase β1 subunit gene

Impairment of transalveolar fluid transport and lung Na⁺-K⁺ATPase function by hypoxia in rats