Alveolar–capillary membrane diffusion measurement by nitric oxide inhalation in heart failure

Abstract

Background

In heart failure, lung diffusion is reduced, it correlates with prognosis and exercise capacity, and it is a therapy target.

Design

Diffusion is measured as CO total diffusion (DL_CO), which has two components: membrane diffusion (Dm) and capillary volume, the latter related to CO and O₂ competition for hemoglobin. DL_CO needs to be corrected for hemoglobin. Diffusion can also be measured with NO (DL_NO), which has a very high affinity for hemoglobin, and thus, the resistance of hemoglobin being trivial, it directly represents Dm. Therefore, Dm is directly calculated from DL_NO through a correction factor. DL_NO has never been measured in heart failure. The study aims at determining, in heart failure, DL_NO, Dm correction factor, and whether Dm_NO provides Dm estimates comparable to Dm_CO.

Methods

We measured DL_CO, Dm_CO by multi-maneuver Roughton–Forster method, and DL_CO and DL_NO by single-breath maneuver in 50 heart failure and 50 healthy subjects.

Results

DL_CO was 21.9 ± 4.8 ml/mmHg per min and 16.8 ± 5.1 in healthy subjects and heart failure subjects, respectively (p < 0.001). DL_NO was 88.6 ± 20.5 ml/mmHg per min and 72.5 ± 22.3, respectively (p < 0.001). The correction factors to obtain Dm from DL_NO were 2.68 (entire population), 2.63 (healthy subjects) and 2.75 (heart failure subjects). Dm_CO and Dm_NO were 34.7 ± 10.9 ml/mmHg per min and 33.8 ± 7.6 in healthy subjects and 25.9 ± 2.0 and 26.4 ± 8.1 in heart failure subjects.

Conclusions

DL_NO and Dm_NO measurements are feasible in heart failure. Dm_CO and Dm_NO provide comparable results. The correction factor to calculate Dm from DL_NO in heart failure is 2.75, which is little different from the 2.63 value we observed in healthy subjects.

Keywords

Oxygen consumption lung diffusion gas exchange

Get full access to this article

View all access options for this article.

References

American Thoracic Society. Single-breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique – 1995 update. Am J Respir Crit Care Med 1995; 152: 2185–2198.

Agostoni

Bussotti

Cattadori

. Gas diffusion and alveolar-capillary unit in chronic heart failure. Eur Heart J 2006; 27: 2538–2543.

Guazzi

. Alveolar-capillary membrane dysfunction in chronic heart failure: Pathophysiology and therapeutic implications. Clin Sci (Lond) 2000; 98: 633–641.

Guazzi

Pontone

Brambilla

. Alveolar–capillary membrane gas conductance: A novel prognostic indicator in chronic heart failure. Eur Heart J 2002; 23: 467–476.

Roughton

Forster

. Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries. J Appl Physiol 1957; 11: 290–302.

Borland

Higenbottam

. A simultaneous single breath measurement of pulmonary diffusing capacity with nitric oxide and carbon monoxide. Eur Respir J 1989; 2: 56–63.

van der Lee

Zanen

Biesma

. The effect of red cell transfusion on nitric oxide diffusing capacity. Respiration 2005; 72: 512–516.

van der Lee

Zanen

Stigter

. Diffusing capacity for nitric oxide: Reference values and dependence on alveolar volume. Respir Med 2007; 101: 1579–1584.

Borland

Dunningham

Bottrill

. Significant blood resistance to nitric oxide transfer in the lung. J Appl Physiol 2010; 108: 1052–1060.

10.

West

. Ventilation-perfusion inequality and overall gas exchange in computer models of the lung. Respir Physiol 1969; 7: 88–110.

11.

Agostoni

Swenson

Bussotti

. High-altitude exposure of three weeks duration increases lung diffusing capacity in humans. J Appl Physiol 2011; 110: 1564–1571.

12.

Puri

Baker

Dutka

. Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance. Circulation 1995; 91: 2769–2774.

13.

Cattadori

Wasserman

Meloni

. Alveolar membrane conductance decreases as BNP increases during exercise in heart failure. Rationale for BNP in the evaluation of dyspnea. J Card Fail 2009; 15: 136–144.

14.

Agostoni

Cattadori

Bianchi

. Exercise-induced pulmonary edema in heart failure. Circulation 2003; 108: 2666–2671.

15.

Agostoni

Magini

Andreini

. Spironolactone improves lung diffusion in chronic heart failure. Eur Heart J 2005; 26: 159–164.

16.

Hughes

Bates

. Historical review: The carbon monoxide diffusing capacity (DLCO) and its membrane (DM) and red cell (Theta.Vc) components. Respir Physiol Neurobiol 2003; 138: 115–142.

17.

Agostoni

Bussotti

Palermo

. Does lung diffusion impairment affect exercise capacity in patients with heart failure? Heart 2002; 88: 453–459.

18.

Miller

Hankinson

Brusasco

. Standardisation of spirometry. Eur Respir J 2005; 26: 319–338.

19.

Dressel

Filser

Fischer

. Lung diffusing capacity for nitric oxide and carbon monoxide: Dependence on breath-hold time. Chest 2008; 133: 1149–1154.

20.

Zavorsky

Murias

. A small amount of inhaled nitric oxide does not increase lung diffusing capacity. Eur Respir J 2006; 27: 1251–1257.

21.

Phansalkar

Hanson

Shakir

. Nitric oxide diffusing capacity and alveolar microvascular recruitment in sarcoidosis. Am J Respir Crit Care Med 2004; 169: 1034–1040.

22.

Tamhane

Johnson

RL Jr

Hsia

. Pulmonary membrane diffusing capacity and capillary blood volume measured during exercise from nitric oxide uptake. Chest 2001; 120: 1850–1856.

23.

Zavorsky

Lands

. Lung diffusion capacity for nitric oxide and carbon monoxide is impaired similarly following short-term graded exercise. Nitric Oxide 2005; 12: 31–38.

24.

Guenard

Varene

Vaida

. Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer. Respir Physiol 1987; 70: 113–120.

25.

Manier

Moinard

Stoicheff

. Pulmonary diffusing capacity after maximal exercise. J Appl Physiol 1993; 75: 2580–2585.

26.

Zavorsky

Quiron

Massarelli

. The relationship between single-breath diffusion capacity of the lung for nitric oxide and carbon monoxide during various exercise intensities. Chest 2004; 125: 1019–1027.

27.

Agostoni

Bianchi

Moraschi

. Work-rate affects cardiopulmonary exercise test results in heart failure. Eur J Heart Fail 2005; 7: 498–504.

28.

Paolillo

Farina

Bussotti

. Exercise testing in the clinical management of patients affected by pulmonary arterial hypertension. Eur J Prev Cardiol 2012; 19: 960–971.

29.

Guazzi

Marenzi

Alimento

. Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. Circulation 1997; 95: 1930–1936.

30.

Agostoni

Palermo

Contini

. Respiratory effects of beta-blocker therapy in heart failure. Cardiovasc Drugs Ther 2009; 23: 377–384.

31.

Agostoni

Guazzi

Bussotti

. Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure. J Am Coll Cardiol 2000; 36: 1600–1604.

32.

Agostoni

Swenson

Fumagalli

. Acute high-altitude exposure reduces lung diffusion: Data from the HIGHCARE Alps Project. Respir Physiol Neurobiol 2013; 188(2): 223–228.

33.

Merrikh

Lage

. Effect of blood flow on gas transport in a pulmonary capillary. J Biomech Eng 2005; 127: 432–439.

34.

Hsia

. Recruitment of lung diffusing capacity: Update of concept and application. Chest 2002; 122: 1774–1783.

35.

Guazzi

Reina

Tumminello

. Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients. Eur J Heart Fail 2005; 7: 1017–1022.

36.

Agostoni

Wasserman

Guazzi

. Exercise-induced hemoconcentration in heart failure due to dilated cardiomyopathy. Am J Cardiol 1999; 83: 278–280, A276.