Can a membrane oxygenator be a model for lung NO and CO transfer?

Abstract

To model lung nitric oxide (NO) and carbon monoxide (CO) uptake, a membrane oxygenator circuit was primed with horse blood flowing at 2.5 l/min. Its gas channel was ventilated with 5 parts/million NO, 0.02% CO, and 22% O2 at 5 l/min. NO diffusing capacity (Dno) and CO diffusing capacity (Dco) were calculated from inlet and outlet gas concentrations and flow rates: Dno = 13.45 ml.min(-1).Torr(-1) (SD 5.84) and Dco = 1.22 ml.min(-1).Torr(-1) (SD 0.3). Dno and Dco increased (P = 0.002) with blood volume/surface area. 1/Dno (P < 0.001) and 1/Dco (P < 0.001) increased with 1/Hb. Dno (P = 0.01) and Dco (P = 0.004) fell with increasing gas flow. Dno but not Dco increased with hemolysis (P = 0.001), indicating Dno dependence on red cell diffusive resistance. The posthemolysis value for membrane diffusing capacity = 41 ml.min(-1).Torr(-1) is the true membrane diffusing capacity of the system. No change in Dno or Dco occurred with changing blood flow rate. 1/Dco increased (P = 0.009) with increasing Po2. Dno and Dco appear to be diffusion limited, and Dco reaction limited. In this apparatus, the red cell and plasma offer a significant barrier to NO but not CO diffusion. Applying the Roughton-Forster model yields similar specific transfer conductance of blood per milliliter for NO and CO to previous estimates. This approach allows alteration of membrane area/blood volume, blood flow, gas flow, oxygen tension, red cell integrity, and hematocrit (over a larger range than encountered clinically), while keeping other variables constant. Although structurally very different, it offers a functional model of lung NO and CO transfer.

TheTL,NO/TL,COratio in pulmonary function test interpretation

“…The assumption that Hbl,NO for red blood cells is infinite cannot, in theory, be correct because of the advancing front phenomenon, i.e. the reaction rate of NO with Hb is so high that, according to MORRIS and GIBSON [8] Experimentally, red blood cell lysis (by the addition of water to blood in a membrane oxygenator model of NO and CO transfer [9]), or red blood cell substitution, in anaesthetised dogs, with cell-free haem based oxyglobin [10] increased TL,NO substantially, but hardly altered TL,CO. This suggested, for NO uptake, that there was significant resistance in the red blood cell membrane, or its interior, or in a stagnant layer of plasma immediately surrounding the cell, and separate from any resistance stemming from the chemical combination with haemoglobin; conversely, most of the red blood cell resistance to CO uptake appeared to be associated with the haemoglobin molecule itself.…”

Alveolar-Membrane Diffusing Capacity Improves in the Morbidly Obese after Bariatric Surgery

“…The DLCO was corrected to the patient's actual hemoglobin concentration using the formulas from the 2005 ATS and ERS Guidelines [11]. We have assumed, as most workers do, that ÈNO in vivo [5,9,[12][13][14][15], although not in vitro [16], is infinity. The likely reason for this discrepancy is facilitated diffusion and/or lack of a stagnant layer in vivo [17].…”

The blood transfer conductance for nitric oxide: Infinite vs. finite θ NO

“…Indeed, it has been demonstrated by multiple groups that the specific blood transfer conductance for NO with free hemoglobin is anywhere from 100 to over 1000 times faster than that with red blood cells, suggesting that the red blood cell does in fact have a meaningful resistance to the diffusion of NO. These studies have been completed in several animal species and using various methods (Azarov et al, 2011; Borland et al, 2006; Borland et al, 2010; Carlsen and Comroe, 1958; Deonikar and Kavdia, 2010; Liu et al, 1998; Vaughn et al, 2000). Accordingly, it has been argued by some researchers that θ NO cannot, by definition, be infinite as a red cell resistance does in fact exist.…”