Significant blood resistance to nitric oxide transfer in the lung

Borland, Colin; Dunningham, Helen; Bottrill, Fiona; Vuylsteke, Alain; Yilmaz, Cüneyt; Dane, D. Merrill; Hsia, Connie C. W.

doi:10.1152/japplphysiol.00904.2009

Cited by 68 publications

(74 citation statements)

References 33 publications

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“…However, it has been estimated that DL NO would not need to be adjusted unless the hemoglobin concentration is Ͻ8 g/dl (50). This is apparent in the data reported by Borland et al (6) and in keeping with previous observation that changes in hemoglobin concentrations like measured in the present study would not be expected to affect DL NO (42).…”

Section: Discussionsupporting

confidence: 89%

“…Most recently, Borland et al (6) reported on membrane oxygenator and experimental animal preparations showing that the replacement of whole blood by hemolyzed blood and cell-free hemoglobin solution actually increased DL NO , with demonstration of a finite value for NO of ϳ4.5 ml NO(ml blood·min·mmHg) Ϫ1 (6). This is similar to that initially reported by Carlsen and Comroe in 1958 (8).…”

Section: Discussionsupporting

confidence: 69%

“…Because the reaction of NO with hemoglobin is quasi-instantaneous, it has been assumed that NO is infinite so that the transfer factor for NO with correction for the NO-to-CO ratio of diffusivity allows for the calculation of Dm, and hence Vc. Recent studies have shown that NO has actually a finite value (6). However, it has been estimated that, for clinical applications in humans, measurements of the diffusing capacity for NO (DL NO ) need adjustment only when the hemoglobin concentration is below 8 g/dl (51).…”

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confidence: 99%

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Improvement in lung diffusion by endothelin A receptor blockade at high altitude

Bisschop

Martinot

Leurquin‐Sterk³

et al. 2012

Journal of Applied Physiology

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de Bisschop C, Martinot J, Leurquin-Sterk G, Faoro V, Guénard H, Naeije R. Improvement in lung diffusion by endothelin A receptor blockade at high altitude. J Appl Physiol 112: 20 -25, 2012. First published October 6, 2011 doi:10.1152/japplphysiol.00670.2011.-Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (V O2 max). The diffusing capacities for nitric oxide (DLNO) and carbon monoxide (DLCO) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DLCO (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DLCO, DLNO, and Dm but a slight decrease in Vc. Exercise at altitude decreased DLNO and Dm. Sitaxsentan intake improved V O2 max together with an increase in resting and postexercise DLNO and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DLNO. Both DLCO and DLNO were correlated to V O2 max at sea level (r ϭ 0.41-0.42, P Ͻ 0.1) and more so at altitude (r ϭ 0.56 -0.59, P Ͻ 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity. altitude; hypoxia; lung diffusion; gas exchange; exercise capacity; pulmonary vascular resistance; pulmonary capillary pressure; pulmonary hypertension BOTH THE MEMBRANE AND THE capillary components of lung diffusing capacity have been shown to be increased in highaltitude residents (10,13,15,25). Increased lung diffusing capacity at high altitude allows for the preservation of gas exchange in the presence of a decreased ventilatory response at exercise (15). High-altitude newcomers do not benefit from this adaptation (10,15,25) and, accordingly, depend on increased ventilation to maintain pulmonary gas exchange (15,45).Previous studies on lung diffusing capacity at high altitudes calculated the membrane and capillary components of alveolocapillary transfer of carbon monoxide (CO) using measurements at ambient air and increased inspired PO 2 (10,13,15,25). This approach rests on the PO 2 dependence of , the blood's specific transfer conductance of CO, in the Roughton and Forster equation, which states that 1/DL CO ϭ 1/Dm ϩ 1/ Vc where DL CO is the diffusing capacity of the lung for CO, Dm its membrane component, and Vc the capillary blood volume (37). Thus changing as by increasing or decreasing inspired PO 2 allows for the calculation of Dm and Vc from a simple system of two equations with two unknowns. However, changing inspired PO 2 might also change pulmonary vascular tone, cardiac output, ...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 69%

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confidence: 99%

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Improvement in lung diffusion by endothelin A receptor blockade at high altitude

Bisschop

Martinot

Leurquin‐Sterk³

et al. 2012

Journal of Applied Physiology

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“…that y NO is infinity, a view originally asserted by the Bordeaux group. 7 Nitric oxide transfer is now known to increase with hemolysis in vitro 8 and with addition of a cell-free blood substitute in vitro and in vivo 9 indicating that y NO is finite and that DL NO < Dm NO . We and the Bordeaux group 10 recommend using the values for y NO and y CO derived from rate constants measured using the Continuous Flow Rapid Reaction apparatus at the University of Pennsylvania.…”

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confidence: 99%

Confusion in reporting pulmonary diffusing capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide

Zavorsky

Borland

2014

Eur J Prev Cardiolog

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We read with interest the paper by Magini and colleagues on the measurement of pulmonary diffusing capacity for nitric oxide in patients with heart failure (ejection fraction<40%).1 In their study they report pulmonary diffusing capacity and the individual components of pulmonary diffusing capacity in 50 patients with heart failure (65 years of age), and 50 control subjects (61 years of age). We feel that there are two problems with this paper that warrant discussion. First, the mean values for pulmonary diffusing capacity for nitric oxide (DL NO ) for the healthy subjects are too low, and second, both their alveolar-membrane conductances (Dm NO and Dm CO ) and pulmonary capillary blood volume (Vc) calculations, and hence conclusions, are incorrect.First, the values for DL NO for the healthy volunteers appear too low. If we assume that the women's and men's mean height in the healthy volunteers was 163 and 173 cm, respectively, then the mean DLNO values should be 96-113 and 140-154 ml/min/mm Hg, for women and men, respectively.2,3 The combined average for DL NO should be then 118-133 ml/min/mm Hg. The author's mean values of 89 ml/min/mm Hg for the healthy volunteers are 25-33% lower than predicted. However, their values for pulmonary diffusing capacity for carbon monoxide (DL CO ) were correct and the healthy volunteers was close to 100% of that predicted.2,3 Thus, if the mean DL NO in the control group is under-predicted by at least 25%, then the DL NO values in the heart failure patients could be under predicted by !25% too. Since DL NO and DL CO are measured simultaneously, and DL CO values were appropriate (close to 100% of those predicted), there must be some mathematical error in the calculation of DL NO and/or their breath-hold time was too short. The breath-hold time should be 5-10 s, 4 and it seems that their breath-hold time varied between 2-4 s.Second, in the discussion they state ''Vcap was unchanged, and the DL NO /DL CO ratio was 4.1 in healthy subjects and 4.4 in heart failure patients.'' Hughes and Van der Lee 5 have elegantly illustrated how DL NO /DL CO is a proxy for Dm/Vc so the only way for the patients in this study to have an unchanged Vc and a raised DL NO /DL CO is for them to have a higher Dm than the normal controls! Clearly Magini et al.'s calculations of Vc (and Dm) are wrong. They have used the 1957 value for y CO ; Forster states that his 1957 value is incorrect and that the 1987 value should be used instead.6 Magini et al. have assumed that DL NO ¼ Dm NO i.e. that y NO is infinity, a view originally asserted by the Bordeaux group.7 Nitric oxide transfer is now known to increase with hemolysis in vitro 8 and with addition of a cell-free blood substitute in vitro and in vivo 9 indicating that y NO is finite and that DL NO < Dm NO . We and the Bordeaux group 10 recommend using the values for y NO and y CO derived from rate constants measured using the Continuous Flow Rapid Reaction apparatus at the University of Pennsylvania. 11 We have recalculated Magini et al.'s data using these ...

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“…We have to admit that we were not able to repeat the calculation done by Zavorsky and Borland using the yNO and yCO values they supplied in the table legend (in reality there must be a typo as yNO and yCO were reported in the legend but only yNO ¼ 4.5 ml ml À1 mm Hg À1 min À1 in the table). In this regard the presence of a defined yNO value, 27 albeit a fascinating issue, is still a matter of debate.…”

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confidence: 99%

Reply to commentary on: Confusion in reporting pulmonary diffusion capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide

Agostoni

Magini

Apostolo

2014

Eur J Prev Cardiolog

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We read with interest the commentary by Gerald Zavorsky and Colin Borland on our paper on lung diffusion for nitric oxide (DLNO) vs lung diffusion for carbon monoxide (DLCO) in normal subjects and in patients with heart failure.1 Both authors are worldwide recognised experts. We are therefore indebted with them for the time and thought they gave to our work. The criticisms that they raise are both methodological and physiological. Indeed, DLNO measurement for clinical purposes has been introduced only a few years ago since the commercial apparatus has been available. Studies about simultaneous DLNO/DLCO evaluation have been conducted with different analysers and different NO concentrations so the method is still far from being standardised. However, we recognise that our DLNO values in normal subjects, obtained in a sizeable number of subjects, are lower than those previously reported by Zavorsky et al. 2 In any case the apparatus we used (Jaeger/Vyasis PFT Masterscreen) was calibrated for gas analysis using automated procedures and the linearity of analysers was factory checked. The formula used is: Concerning breath hold time, we used 4 s, which is the same as Aguilaniu et al. 8 used whose data were the basis of the normal standards for European equations for carbon monoxide (CO) and nitric oxide (NO). Anyway, with a longer breath hold time we would expect an underestimation of DLNO, as reported by Dressler et al., 9 and not an overestimation as suggested by Zavorsky and Borland. In fact as breath hold time is increased, NO expiratory concentration reduces, reaching the detection limit of the NO analyser. This is an issue when using electrochemical sensors, as we 1 and others did, 2,5,8 and not with a highsensitivity chemiluminescence NO analyser as other authors did. 10,11 As regards the membrane diffusion for carbon monoxide (DmCO), membrane diffusion for nitric oxide (DmNO) and capillary volume (Vcap), we prefer to call the capillary volume Vcap and not Vc as frequently done to avoid confusion with the vital capacity, and we do not agree with the Zavorsky and Borland critique. We recognise, however, that we erroneously quoted, and always have done so previously, the original paper by Roughton and Forster 12 but actually used the more recent description of DLCO partitioning.

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Significant blood resistance to nitric oxide transfer in the lung

Abstract: Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNO Show more

Cited by 68 publications

References 33 publications

Improvement in lung diffusion by endothelin A receptor blockade at high altitude

Improvement in lung diffusion by endothelin A receptor blockade at high altitude

Confusion in reporting pulmonary diffusing capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide

Reply to commentary on: Confusion in reporting pulmonary diffusion capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide

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