Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation-perfusion matching.

After pneumonectomy (Pnx), mechanical strain on the remaining lung is an important signal for adaptation. To examine how mechanical lung strain alters gas exchange adaptation after Pnx, we replaced the right lung of adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis was kept 1) inflated (Inf) to reduce mechanical strain of the remaining lung and maintain the mediastinum in the midline, or 2) deflated (Def) to allow lung strain and mediastinal shift. Gas exchange was studied 4-7 mo later at rest and during treadmill exercise by the multiple inert gas elimination technique while animals breathed 21 and 14% O2 in balanced order. In the Inf group compared with Def group during hypoxic exercise, arterial O2 saturation was lower and alveolar-arterial O2 tension difference higher, whereas O2 diffusing capacity was lower at any given cardiac output. Dispersion of the perfusion distribution was similar between groups at rest and during exercise. Dispersion of the ventilation distribution was lower in the Inf group at rest, associated with a much higher respiratory rate, but rose to similar levels in both groups during hypoxic exercise. Mean pulmonary arterial pressure at a given cardiac output was higher in the Inf group, whereas peak cardiac output was similar between groups. Thus creating lung strain by post-Pnx mediastinal shift primarily enhances diffusive gas exchange with only minor effects on ventilation-perfusion matching, consistent with the generation of additional alveolar-capillary surfaces but not conducting airways and blood vessels.     

Density-dependent reduction of nitric oxide diffusing capacity after pneumonectomy.

Airway lengthening after pneumonectomy (PNX) may increase diffusive resistance to gas mixing (1/D(G)); the effect is accentuated by increasing acinar gas density but is difficult to detect from lung CO-diffusing capacity (Dl(CO)). Because lung NO-diffusing capacity (Dl(NO)) is three- to fivefold that of Dl(CO), whereas 1/D(G) for NO and CO are similar, we hypothesized that a density-dependent fractional reduction would be greater for Dl(NO) than for Dl(CO). We measured Dl(NO) and Dl(CO) at two tidal volumes (Vt) and with three background gases [helium (He), nitrogen (N(2)), and sulfur hexafluoride (SF(6))] in immature dogs 3 and 9 mo after right PNX (5 and 11 mo of age). At maturity (11 mo), background gas density had no effect on Dl(NO), Dl(CO), or Dl(NO)-to-Dl(CO) ratio in sham controls. In PNX animals, Dl(NO) declined 25-50% in SF(6) relative to He and N(2), and Dl(NO)/Dl(CO) declined approximately 50% in SF(6) relative to He at a Vt of 15 ml/kg, consistent with a significant 1/D(G). At 5 mo of age, Dl(NO)/Dl(CO) declined 25-45% in SF(6) relative to He and N(2) in both groups, but Dl(CO) increased paradoxically in SF(6) relative to N(2) or He by 20-60%. Findings suggest that SF(6), besides increasing 1/D(G), may redistribute ventilation and/or enhance acinar penetration of the convective front.     

Steady-state measurement of NO and CO lung diffusing capacity on moderate exercise in men.

Using a rapidly responding nitric oxide (NO) analyzer, we measured the steady-state NO diffusing capacity (DL(NO)) from end-tidal NO. The diffusing capacity of the alveolar capillary membrane and pulmonary capillary blood volume were calculated from the steady-state diffusing capacity for CO (measured simultaneously) and the specific transfer conductance of blood per milliliter for NO and for CO. Nine men were studied bicycling at an average O(2) consumption of 1.3 +/- 0.2 l/min (mean +/- SD). DL(NO) was 202.7 +/- 71.2 ml. min(-1). Torr(-1) and steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO(2), mixed expired CO(2), and mixed expired CO, was 46.9 +/- 12.8 ml. min(-1). Torr(-1). NO dead space = (VT x FE(NO) - VT x FA(NO))/(FI(NO) - FA(NO)) = 209 +/- 88 ml, where VT is tidal volume and FE(NO), FI(NO), and FA(NO) are mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO(2) dead space from mixed exhaled and end-tidal (assumed alveolar) CO(2) = 430 +/- 136 ml. Predicted anatomic dead space = 199 +/- 22 ml. Membrane diffusing capacity was 333 and 166 ml. min(-1). Torr(-1) for NO and CO, respectively, and pulmonary capillary blood volume was 140 ml. Inhalation of repeated breaths of NO over 80 s did not alter DL(NO) at the concentrations used.     

Noninvasive diffusing capacity and cardiac output in exercising dogs

We have developed a rebreathing procedure to determine diffusing capacity (DLCO) and pulmonary blood flow (Qc) in the awake, exercising dog. A low dead space, leak-free respiratory mask with an incorporated mouthpiece was utilized to achieve mixing between the rebreathing bag and the dog's lung. The rebreathing bag was initially filled with approximately 1.0 liter of gas containing 0.6% C2H2, 0.3% C18O, 9% He, and 35-40% O2. End-tidal gas concentrations were measured with a respiratory mass spectrometer. The disappearance of C2H2 and C18O was measured with respect to He to calculate Qc and DLCO. Values for DLCO in dogs, expressed per kilogram of body weight, were much larger than those reported in humans. However, at a given level of absolute O2 consumption, measurements of absolute DLCO in dogs were comparable to those reported in humans by both rebreathing and steady-state methods at rest and near-maximal exercise. These results suggest that DLCO is more closely matched to the metabolic capacity (i.e., maximal O2 consumption) than to body size between these two species.     

Allometric analysis of the morphometric pulmonary diffusing capacity in dogs

The lung volume, the morphometrically determined alveolar and capillary surface area, and the capillary volume of 27 dogs (weight 2.65–57 kg) all were linearly correlated with body weight. The thickness of the air-blood barrier increased only slightly with increasing body size. The structural diffusing capacity, containing these parameters, was used to estimate the gas exchange capabilities of the lung and was also found to scale in direct proportion to body size. This coincides with reports on physiologically estimated diffusing capacity but is obviously different from the interspecies slope for metabolism which scales to the 3/4 power of body weight.     

Pulmonary diffusing capacity and capillary blood volume in aging dogs.

Single-breath carbon monoxide diffusing capacity (DLco), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) were measured in 24 beagle dogs aged 289-3,882 days. DLco and Vc were a function of age and alveolar volume (Va). Vc decreased with age resulting in changes in DLco. Changes in Vc may have been due to pulmonary morphological changes or to an exaggerated decrease in pulmonary blood flow in old dogs in response to 20-30 cmH-2O transpulmonary pressure. There was no age-related change in Dm.     

An open-circuit method for determining lung diffusing capacity during exercise: comparison to rebreathe.

To avoid limitations associated with the use of single-breath and rebreathe methods for assessing the lung diffusing capacity for carbon monoxide (D(L)CO) during exercise, we developed an open-circuit technique. This method does not require rebreathing or alterations in breathing pattern and can be performed with little cognition on the part of the patient. To determine how this technique compared with the traditional rebreathe (D(L)CO,RB) method, we performed both the open-circuit (D(L)CO,OC) and the D(L)CO,RB methods at rest and during exercise (25, 50, and 75% of peak work) in 11 healthy subjects [mean age = 34 yr (SD 11)]. Both D(L)CO,OC and D(L)CO,RB increased linearly with cardiac output and external work. There was a good correlation between D(L)CO,OC and D(L)CO,RB for rest and exercise (mean of individual r2 = 0.88, overall r2 = 0.69, slope = 0.97). D(L)CO,OC and D(L)CO,RB were similar at rest and during exercise [e.g., rest = 27.2 (SD 5.8) vs. 29.3 (SD 5.2), and 75% peak work = 44.0 (SD 7.0) vs. 41.2 ml.min(-1).mmHg(-1) (SD 6.7) for D(L)CO,OC vs. D(L)CO,RB]. The coefficient of variation for repeat measurements of D(L)CO,OC was 7.9% at rest and averaged 3.9% during exercise. These data suggest that the D(L)CO,OC method is a reproducible, well-tolerated alternative for determining D(L)CO, particularly during exercise. The method is linearly associated with cardiac output, suggesting increased alveolar-capillary recruitment, and values were similar to the traditional rebreathe method.     

Exercise-induced oxyhemoglobin desaturation and pulmonary diffusing capacity during high-intensity exercise

The purpose of this investigation was to examine if exercise-induced arterial oxyhemoglobin desaturation selectively observed in highly trained endurance athletes could be related to differences in the pulmonary diffusing capacity (D _L) measured during exercise. The D _L of 24 male endurance athletes was measured using a 3-s breath-hold carbon monoxide procedure (to give D _LCO) at rest as well as during cycling at 60% and 90% of these previously determined O_2max. Oxyhemoglobin saturation (S _aO₂%) was monitored throughout both exercise protocols using an Ohmeda Biox II oximeter. Exercise-induced oxyhemoglobin desaturation (DS) (S _aO₂% < 91% at O_2max) was observed in 13 subjects [88.2 (0.6)%] but not in the other 11 nondesaturation subjects [NDS: 92.9 (0.4)%] (P ≤ 0.05), although O_2max was not significantly different between the groups [DS: 4.34 (0.65) l / min vs NDS: 4.1 (0.49) l / min]. At rest, no differences in either D _LCO [m1 CO · mmHg⁻¹ · min⁻¹: 41.7 (1.7) (DS) vs 41.1 (1.8) (NDS)], D _LCO / _A [8.2 (0.4) (DS) vs 7.3 (0.9) (NDS)], MVV [l / min: 196.0 (10.4) (DS) vs 182.0 (9.9) (NDS)] or FEV₁/FVC [86.3 (2.2) (DS) vs 82.9 (4.7) (NDS)] were found between groups (P ≥ 0.05). However, _E /O₂ at O_2max was lower in the DS group [33.0 (1.1)] compared to the NDS group [36.8 (1.5)] (P ≤ 0.05). Exercise D _LCO (m1 CO · mmHg⁻¹ · min⁻¹) was not different between groups at either 60% O_2max [DS: 55.1 (1.4) vs NDS: 57.2 (2.1)] or at 90% O_2max [DS: 61.0 (1.8) vs NDS: 61.4 (2.9)]. A significant relationship (r = 0.698) was calculated to occur between S _aO₂% and _E /O₂ during maximal exercise. The present findings indicate that the exercise-induced oxyhemoglobin desaturation seen during submaximal and near-maximal exercise is not related to differences in D _L, although during maximal exercise S _aO₂ may be limited by a relatively lower exercise ventilation. Accepted: 25 September 1996     

Effect of pneumonectomy on the remaining lung in dogs

To determine the magnitude of functional compensation after pneumonectomy and whether compensation is related to maturity of the animal at the time of resection, we performed left pneumonectomy in either adult or 10-wk-old beagles. Studies were performed in adults 7-9 mo after surgery and in puppies 18-23 mo after surgery when the dogs reached full maturity. Results were compared with those in age- and sex-matched unoperated controls. Measurements included pressure-volume relationships, pulmonary hemodynamics, rebreathing studies of lung volume, diffusing capacity and its components, lung tissue volume, and pulmonary blood flow. Computerized-tomographic scans were performed in the puppy groups to determine changes in thoracic shape and size. Morphometric analysis of the lungs was performed under light microscopy. There was partial compensation for loss of one lung by functional improvement in the remaining lung. Compensation was greater in those pneumonectomized as puppies than as adults. Volume of the remaining lung was larger than predicted for a given transpulmonary pressure in both groups. Diffusing capacity, pulmonary capillary blood volume, and lung tissue volume were larger than expected for the normal right lung. After pneumonectomy, compliance of the rib cage was greater in puppies than in adults. Weight of the costal diaphragm was reduced in pneumonectomized puppies. Pulmonary hypertension at rest did not develop, and pulmonary vascular reactivity to hypoxia was unchanged after pneumonectomy in both groups. Significant correlations were obtained between physiological and morphometric measurements.     

Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure.

Chronic heart failure (CHF) may impair lung gas diffusion, an effect that contributes to exercise limitation. We investigated whether diffusion improvement is a mechanism whereby physical training increases aerobic efficiency in CHF. Patients with CHF (n = 16) were trained (40 min of stationary cycling, 4 times/wk) for 8 wk; similar sedentary patients (n = 15) were used as controls. Training increased lung diffusion (DlCO, +25%), alveolar-capillary conductance (DM, +15%), pulmonary capillary blood volume (VC, +10%), peak exercise O2 uptake (peak VO2, +13%), and VO2 at anaerobic threshold (AT, +20%) and decreased the slope of exercise ventilation to CO2 output (VE/VCO2, -14%). It also improved the flow-mediated brachial artery dilation (BAD, from 4.8 +/- 0.4 to 8.2 +/- 0.4%). These changes were significant compared with baseline and controls. Hemodynamics were obtained in the last 10 patients in each group. Training did not affect hemodynamics at rest and enhanced the increase of cardiac output (+226 vs. +187%) and stroke volume (+59 vs. +49%) and the decrease of pulmonary arteriolar resistance (-28 vs. -13%) at peak exercise. Hemodynamics were unchanged in controls after 8 wk. Increases in DlCO and DM correlated with increases in peak VO2 (r = 0.58, P = 0.019 and r = 0.51, P = 0.04, respectively) and in BAD (r = 0.57, P < 0.021 and r = 0.50, P = 0.04, respectively). After detraining (8 wk), DlCO, DM, VC, peak VO2, VO2 at AT, VE/VCO2 slope, cardiac output, stroke volume, pulmonary arteriolar resistance at peak exercise, and BAD reverted to levels similar to baseline and to levels similar to controls. Results document, for the first time, that training improves DlCO in CHF, and this effect may contribute to enhancement of exercise performance.