Effect of inspiratory resistance and PEEP on 99mTc-DTPA clearance

Experiments were performed to determine the effect of markedly negative pleural pressure (Ppl) or positive end-expiratory pressure (PEEP) on the pulmonary clearance (k) of technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). A submicronic aerosol containing 99mTc-DTPA was insufflated into the lungs of anesthetized intubated sheep. In six experiments k was 0.44 +/- 0.46% (SD)/min during the initial 30 min and was unchanged during the subsequent 30-min interval [k = 0.21 +/- 12%/min] when there was markedly increased inspiratory resistance. A 3-mm-diam orifice in the inspiratory tubing created the resistance. It resulted on average in a 13-cmH2O decrease in inspiratory Ppl. In eight additional experiments sheep were exposed to 2, 10, and 15 cmH2O PEEP (20 min at each level). During 2 cmH2O PEEP k = 0.47 +/- 0.15%/min, and clearance increased slightly at 10 cmH2O PEEP [0.76 +/- 0.28%/min, P less than 0.01]. When PEEP was increased to 15 cmH2O a marked increase in clearance occurred [k = 1.95 +/- 1.08%/min, P less than 0.001]. The experiments demonstrate that markedly negative inspiratory pressures do not accelerate the clearance of 99mTc-DTPA from normal lungs. The effect of PEEP on k is nonlinear, with large effects being seen only with very large increases in PEEP.     

High-frequency oscillatory ventilation increases canine pulmonary epithelial permeability

To investigate the effect of high-frequency oscillatory ventilation (HFOV) on the pulmonary epithelial permeability, we measured the clearance rate of nebulized sodium pertechnetate (99mTcO4-) and diethylenetriaminepentaacetate (99mTc-DTPA) before and after a 4-h period of mechanical ventilation in anesthetized mongrel dogs. The animals also underwent experiments with 4 h of spontaneous breathing (SB) and intermittent positive-pressure ventilation (IPPV) with and without addition of positive end-expiratory pressure (PEEP) for comparison. After IPPV and SB there was no change in the clearance rate of either 99mTcO4- or 99mTc-DTPA. After IPPV + PEEP and HPOV (8 and 16 Hz), there was an increase in the clearance rate of 99mTc-DTPA, but an increase in clearance rate of 99mTcO4- was seen after IPPV + PEEP only. In a separate group of dogs an increase in end-tidal lung volume was demonstrated after 4 h of ventilation with IPPV + PEEP (but not after HFOV), and this may account for the measured increase in 99mTcO4- clearance. We conclude that an increase in 99mTc-DTPA clearance rate after HFOV signifies an increase in pulmonary epithelial permeability, possibly through the mechanism of damage to the intercellular junctions during HFOV.     

Comparison of three tracers for detecting lung epithelial injury in anesthetized sheep

We compared the ability of three aerosolized tracers to discriminate among control, lung inflation with a positive end expired pressure of 10 cmH2O, lung vascular hypertension and edema without lung injury, and lung edema with lung injury due to intravenous oleic acid. The tracers were 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt 492), 99mTc-human serum albumin (99mTc-ALB, mol wt 69,000), and 99mTc-aggregated albumin (99mTc-AGG ALB, mol wt 383,000). 99mTc-DTPA clearance measurements were not able to discriminate lung injury from lung inflation. The 99mTc-AGG ALB clearance rate was unchanged by lung inflation and increased slightly with lung injury. The 99mTc-ALB clearance rate (0.06 +/- 0.02%/min) was unchanged by lung inflation (0.09 +/- 0.02%/min, P greater than 0.05) or 4 h of hypertension without injury (0.09 +/- 0.04%/min, P greater than 0.05). Deposition of 99mTc-ALB within 15 min of the administration of the oleic acid increased the clearance rate to 0.19 +/- 0.06%/min, which correlated well with the postmortem lung water volume (r = 0.92, P less than 0.01). This did not occur when there was a 60-min delay in the deposition of 99mTc-ALB. We conclude that 99mTc-ALB is the best indicator for studying the effects of lung epithelial injury on protein and fluid transport into and out of the air spaces of the lungs in a minimally invasive manner.     

Influence of chest background on pulmonary 99mTc-DTPA clearance in interstitial lung disease.

We examined the effect of chest extracellular 99mTc-diethylenetriamine pentaacetate (DTPA) as a background in the measurement of pulmonary 99mTc-DTPA clearance in patients with interstitial lung disease (ILD). Eight healthy nonsmokers (HN) and eight patients with ILD were studied. We monitored changes in gamma counts after the inhalation of 99mTc-DTPA aerosol by using a gamma camera placed over the anterior chest. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was assessed by calculating the slope of the decrease in the gamma counts. The chest background, estimated by 99mTc-DTPA intravenous injection, was subtracted from the original data to obtain the corrected DTPA clearance (kc; %/min). In patients with ILD, k was significantly greater [2.19 +/- 1.03 (SD) %/min; n = 8] compared with HN (0.86 +/- 0.17%/min; n = 8; P < 0.01). In patients with ILD, kc was also greater (2.80 +/- 1.15%/min; n = 8; P < 0.01) compared with HN (1.20 +/- 0.12%/min; n = 8). There was no difference in percent underestimation of k between the two groups (29.1 +/- 8.8% for HN, 22.5 +/- 7.9% for patients with ILD). There was a significant correlation between k and kc among all subjects (r = 0.987, P < 0.01). We conclude that background causes significant underestimation of pulmonary 99mTc-DTPA clearance.     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.     

Effect of raised thoracic pressure and volume on 99mTc-DTPA clearance in humans

Although positive airway pressure is often used to treat acute pulmonary edema, the effects on epithelial solute flux are not well known. We measured independently the effect of 1) positive pressure and 2) voluntary hyperinflation on the clearance of inhaled technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) in six nonsmokers and six smokers. Lung volumes were monitored by inductance plethysmography. Each subject was studied in four situations: 1) low end-expiratory volume (LO-), 2) low volume plus 9 cmH2O continuous positive airway pressure (LO+), 3) high end-expiratory volume (HI-), and 4) high volume plus continuous positive airway pressure (HI+). The clearance half time of 99mTc-DTPA for the nonsmokers decreased from 64.8 +/- 7.0 min (mean +/- SE) at LO- to 23.2 +/- 5.3 min at HI- (P less than 0.05). Positive pressure had no synergistic effect. The mean clearance half time for the smokers was faster than nonsmokers at base line but unaffected by similar changes in thoracic volume and pressure. We conclude that, in nonsmokers, positive airway pressure increases 99mTc-DTPA clearance primarily through an increase in lung volume and that smokers are immune to these effects.     

Lung epithelial permeability to aerosolized solutes: relation to position

The lung epithelial permeability to inhaled solutes is primarily attributed to the degree of distension of the interepithelial junctions and thus of the alveolar volume. To assess this hypothesis, a submicronic aerosol of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) was inhaled by eight normal subjects in left lateral decubitus (LLD). The regional lung clearance of 99mTc-DTPA was measured in LLD, then in right lateral decubitus (RLD) to reverse the relative distension of the alveoli. Although in LLD the deposition of the aerosol is the greatest in the gravity-dependent regions of the left lung, their 99mTc-DTPA clearances are significantly lower than those of the nondependent regions of the right lung (0.7 +/- 0.3 vs. 2 +/- 0.8%/min, P less than 0.001). In RLD, these regions placed in opposite positions significantly reversed their clearances (1.6 +/- 0.8 vs. 0.6 +/- 0.2%/min, P less than 0.001). Results indicate in lateral decubitus a gravity gradient of 99mTc-DTPA clearances independent of the aerosol deposition. This gradient of epithelial permeability to solutes appears to be influenced by the gradient of alveolar volume.     

Effect of increased surface tension and assisted ventilation on 99mTc-DTPA clearance

Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of 99mTc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. 99mTc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP [k = 7.57 +/- 0.71%/min (SE)] and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of 99mTc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.     

Bradykinin is degraded in hypoxic lungs and does not affect epithelial permeability

To investigate the effect of intravenous infusions of bradykinin (BK) on the permeability of the hypoxic pulmonary epithelium to small solutes, experiments (n = 7) were performed in yearling sheep with chronic vascular catheters. Sheep were anesthetized, intubated, paralyzed, and ventilated. After establishing stable and normal base-line pulmonary hemodynamics and blood gas tensions, the lungs were insufflated with a submicronic aerosol of technetium-99m-labeled diethylenetriaminepentaacetate (99mTc-DTPA, mol wt = 492). Radioactivity arising from the right hemithorax was measured by an NaI probe with a parallel-holed collimator. The base-line pulmonary clearance rate (k) for 99mTc-DTPA was 0.51 +/- 0.09% (SE)/min, while the sheep were ventilated with a fractional concentration of inspired O2 (FIO2) of 0.5 [arterial partial pressure of O2 (PaO2) = 196 +/- 11.4 (SE) Torr]. Clearance of 99mTc-DTPA was unaffected by hypoxia alone or BK infusions in nonhypoxic lungs. The combination of an intravenous infusion of BK at either 1.2 (n = 3) or 2.4 micrograms . kg-1 . min-1 (n = 4) and alveolar hypoxia [FIO2 = 0.11, PaO2 = 28 +/- 1.6 (SE) Torr] did not affect pulmonary clearance of 99mTc-DTPA [k = 0.43 +/- 0.08% (SE)/min]. In contrast, a 0.05-ml/kg intravenous infusion of oleic acid increased clearance 10-fold in one sheep. During combined hypoxia and BK infusion the pulmonary arterial BK concentration (radioimmunoassay) increased from 0.82 +/- 0.16 (SE) to 7.05 +/- 1.86 ng/ml (P less than 0.001), but the systemic arterial concentrations were unchanged [0.67 +/- 0.19 (SE) to 0.66 +/- 0.09 ng/ml].(ABSTRACT TRUNCATED AT 250 WORDS)     

Site of deposition and factors affecting clearance of aerosolized solute from canine lungs

We determined the influence of several factors on lung solute clearance using aerosolized 99mTc-diethylenetriaminepentaacetate. We used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 micron, administered the aerosol in a standard fashion, and determined clearance half times (t1/2) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: 1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (VT) = 15 ml/kg during solute clearance; 2) repeat control, for reproducibility; 3) increased frequency, with f = 25 breaths/min and VT = 10 ml/kg; 4) positive end-expiratory pressure (PEEP) of 10 cmH2O; 5) unilateral pulmonary arterial occlusion (PAO); and 6) bronchial arterial occlusion (BAO). Control t1/2 was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t1/2 to 13 +/- 3 min (P less than 0.01), and PAO increased it to 37 +/- 6 min (P less than 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow.     

Altered pulmonary epithelial permeability in canine radiation lung injury

A radioaerosol scanning technique measuring regional clearance of sodium pertechnetate (99mTcO-4) and 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) was used to assess changes in canine pulmonary epithelial permeability following lung irradiation. Doses of 2,000 cGy (11 dogs), 1,000 cGy (2 dogs), and 500 cGy (2 dogs) were given in one fraction to either the entire right hemithorax (500 cGy) or the right lower lung (1,000 and 2,000 cGy). Radioaerosol scans, chest roentgenograms, and computerized tomograms (CT) were obtained before and serially after irradiation. A dose of 2,000 cGy resulted in a decrease in regional pulmonary epithelial permeability to both 99mTcO4- and 99mTc-DTPA; both showed significant decreases from the 2nd wk postirradiation onward. In comparison, CT and chest roentgenogram did not become abnormal until 7.1 +/- 2.8 (SD) and 8.2 +/- 2.6 wk, respectively. Doses of 1,000 and 500 cGy produced reversible decreases in 99mTcO4- clearance. Lung morphology showed definite changes of radiation pneumonitis after 2,000 and 1,000 cGy but not after 500 cGy at approximately 9, 17, and 12 wk postirradiation, respectively. These results suggest that dose-dependent changes in pulmonary physiology may precede obvious structural alterations in radiation lung injury.     

Pulmonary clearance of radiotracers after positive end-expiratory pressure or acute lung injury

In anesthetized rabbits we measured clearance from lung to blood of eight aerosolized technetium-99m-labeled compounds: diethylenetriaminepentaacetate (99mTc-DTPA); cytochrome c; myoglobin; a myoglobin polymer; albumin; and anionic, cationic, and neutral dextrans of equivalent molecular size. We investigated the effect of applying positive end-expiratory pressure (PEEP) and, on a subsequent occasion, of injecting oleic acid intravenously to produce acute lung injury on the pulmonary clearance rate. Base-line clearance rates were monoexponential and varied with the molecular weights of the radiotracers. For each tracer the rate of clearance was increased a similar degree by either PEEP or oleic acid. However, with PEEP, clearance remained monoexponential, whereas after oleic acid, smaller molecular-weight radiotracers had multiexponential clearance curves. This suggests that after oleic acid the alveolar epithelium breaks down in a nonuniform fashion. We conclude that differentiation of the effect of PEEP from that of severe lung injury caused by oleic acid is not readily accomplished by either increasing the size of the tracer molecule or by varying the molecular charge.     

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.     

Pulmonary clearance of inhaled 99mTc-DTPA: effects of surfactant depletion by lung lavage

The influence of surfactant depletion on clearance from the lungs of inhaled technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) was studied in rabbits. Surfactant was removed by repeated lung lavage with isotone saline. To minimize structural damage to the lungs, pressure generated insufflation with short expiration was utilized. Aerosolized 99mTc-DTPA was administered via a bag-in-bottle system. Radioactivity was measured with a gamma camera and time-activity curves were obtained over the base of the right lung. Six nonlavaged rabbits served as controls. In six lavaged rabbits clearance of 99mTc-DTPA was significantly faster than in controls. In three rabbits given natural surfactant into the trachea after lung lavage, 99mTc-DTPA was eliminated faster than in controls but slower than in surfactant-depleted animals. The results indicate a role of surfactant on clearance rate of 99mTc-DTPA from rabbit lungs. Measurements of 99mTc-DTPA clearance may be useful in studying the function of the surfactant system in different lung disorders.     

Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen

Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema. The time course of development of increased solute flux was assessed by the clearance of 99mTc-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung. These end points were related to the development of pulmonary edema by the measurement of the wet-to-dry weight ratio of the lung and the weight of fluid in the pleural cavity. No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred. By 60 h of exposure, pleural effusions had developed. The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux.     

Effect of superior vena caval hypertension on alloxan-induced lung injury in dogs

To investigate how fast and to what extent superior vena caval hypertension (SVCH) increases lung water in acute increased-permeability state, we studied the time course of lung water accumulation for 3 h in anesthetized dogs under different treatments: 1) controls without intervention (5 dogs), 2) SVCH alone (5 dogs), 3) mild lung microvascular injury induced by low-dose alloxan (75 mg/kg) alone (5 dogs), and 4) SVCH coupled with low-dose alloxan (5 dogs). Neither low-dose alloxan alone nor SVCH alone [superior vena caval pressure (Psvc) = 11.0 +/- 3.1 (SD) mmHg] increased lung water significantly. The SVCH coupled with low-dose alloxan (Psvc = 11.3 +/- 2.7 mmHg) doubled extravascular lung thermal volume measured by the thermal-dye dilution technique within 1 h (5.3 +/- 0.9 ml/kg at base line and 10.9 +/- 4.7 ml/kg at 1 h), then remained unchanged (12.5 +/- 5.7 ml/kg at 3 h). This increase in lung water was confirmed by gravimetric method (5.69 +/- 1.71 g/g blood-free dry wt). We conclude that SVCH is one of the factors that may promote lung water accumulation in increased-permeability state.     

Endotoxin-pretreated neutrophils increase pulmonary vascular permeability in dogs

Endotoxin causes pulmonary vascular neutrophil sequestration and injures the lung. Whether this is primarily due to a direct effect of endotoxin on the endothelium or is mediated by an action on the neutrophil is unclear. Canine neutrophils, isolated on plasma-Percoll gradients in vitro, were incubated with Salmonella enteriditis endotoxin, washed, and injected via wedged pulmonary arterial catheters into discrete lung zones of anesthetized dogs, whereas untreated neutrophils were administered into contralateral control lung zones. 113mIn-transferrin was administered intravenously 2 h before the animals were killed. Morphometry and extravascular protein accumulation were assessed at 4 h. Endotoxin treatment of neutrophils ex vivo induced a two- to three-fold increase in neutrophils in these lung zones (0.096 +/- 0.012 vs. 0.05 +/- 0.002 neutrophils/alveolar septal intercept, P less than 0.05). Extravascular-to-intravascular protein ratios in zones receiving endotoxin-treated neutrophils were significantly increased compared with control zones (0.146 +/- 0.02 vs. 0.079 +/- 0.02, P less than 0.05). Because complement fragments increase injury to endothelium in vitro, exogenous C5 fragments were administered to other dogs before administration of neutrophils but failed to significantly increase the extravascular protein signal (0.154 +/- 0.03 vs. 0.124 +/- 0.04). In summary, endotoxin treatment of neutrophils leads to neutrophil sequestration and increased pulmonary extravascular protein accumulation. C5 fragments failed to further enhance the protein accumulation. These data are consistent with an effect of endotoxin on the neutrophil to initiate neutrophil-endothelial interaction and subsequent lung injury.     

Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs

We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the "hillocks" method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response.     

Interdependence of bronchial circulation and clearance of 99mTc-DTPA from the airway surface.

The extent to which the systemic vasculature is involved in soluble-particle uptake in the conducting airways has not been studied extensively. In anesthetized, ventilated sheep, 6-10 microl of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) was delivered through a microspray nozzle to a fourth-generation airway. Perfusion of the cannulated bronchial artery was varied between control flow (0.6 ml x min(-1) x kg(-1)), high flow (1.8 ml x min(-1) x kg(-1)) or no flow (the infusion pump was stopped). Airway retention of the radioactive tracer was monitored using gamma camera imaging, and venous blood was sampled. During control perfusion, tracer retention at the site of deposition at 30 min averaged 20 +/- 6% (n = 7). With no flow, retention was significantly elevated to 32 +/- 8% (P = 0.03). In another group of sheep (n = 5) with a control retention of 13 +/- 4%, high flow resulted in an increase in tracer (25 +/- 4%; P = 0.04). Maximum blood uptake of tracer was calculated by estimating circulating blood volume and averaged 16% of total activity during control flow. Only during high-flow conditions was 99mTc-DTPA in the blood decreased (10%; P = 0.04). Most of the tracer was cleared by mucociliary clearance as visualized by imaging. This component was substantially decreased during no flow. The results demonstrate that both decreased and increased airway perfusion limit removal of soluble tracer applied to the conducting airways.     

Alveolar epithelial integrity in athletes with exercise-induced hypoxemia.

The effect of incremental exercise to exhaustion on the change in pulmonary clearance rate (k) of aerosolized (99m)Tc-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) and the relationship between k and arterial PO(2) (Pa(O(2))) during heavy work were investigated. Ten male cyclists (age = 25 +/- 2 yr, height = 180.9 +/- 4.0 cm, mass = 80.1 +/- 9.5 kg, maximal O(2) uptake = 5. 25 +/- 0.35 l/min, mean +/- SD) completed a pulmonary clearance test shortly (39 +/- 8 min) after a maximal O(2) uptake test. Resting pulmonary clearance was completed >/=24 h before or after the exercise test. Arterial blood was sampled at rest and at 1-min intervals during exercise. Minimum Pa(O(2)) values and maximum alveolar-arterial PO(2) difference ranged from 73 to 92 Torr and from 30 to 55 Torr, respectively. No significant difference between resting k and postexercise k for the total lung (0.55 +/- 0.20 vs. 0. 57 +/- 0.17 %/min, P > 0.05) was observed. Pearson product-moment correlation indicated no significant linear relationship between change in k for the total lung and minimum Pa(O(2)) (r = -0.26, P > 0.05). These results indicate that, averaged over subjects, pulmonary clearance of (99m)Tc-DTPA after incremental maximal exercise to exhaustion in highly trained male cyclists is unchanged, although the sampling time may have eliminated a transient effect. Lack of a linear relationship between k and minimum Pa(O(2)) during exercise suggests that exercise-induced hypoxemia occurs despite maintenance of alveolar epithelial integrity.