Alveolar-arterial O2 Tension Difference Research Articles

Effects of cardiopulmonary bypass on lung nuclear factor-kappa B activity, cytokine release, and pulmonary function in dogs.

To study the effect of cardiopulmonary bypass (CPB) on nuclear factor-kappa B (NF-κB) and cytokine expression and pulmonary function in dogs. Twelve male mongrel dogs were divided into a methylprednisolone group (group M) and a control group (group C). All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated. The activity of NF-κB and myeloperoxidase (MPO), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8, and the wet/dry (W/D) weight ratio were significantly higher after CPB than before CPB in both groups (P<0.01), with the lower values in group M than in group C, at different time points (P<0.01). Histological evaluation revealed neutrophilic infiltration and thickening of the alveolar interstitium in both groups; however, the degree of pathological changes was significantly lower in group M than in group C. The alveolar-arterial O2 tension difference (PA-aDO2) was significantly higher after CPB than before CBP (P<0.01), and lower in group M than in group C (P<0.01). The pulmonary compliance after removal of the aortic clamp obviously decreased in group C (P<0.05), with no significant change in group M. CPB can significantly enhance the activation of NF-κB in lung tissues and increase the expression of inflammatory cytokines, thus inducing lung injury. Methylprednisolone can inhibit the NF-κB activation, thus inhibiting the release of cytokines and protecting the lung function.

Influences of pleural effusion on respiratory mechanics, gas exchange, hemodynamics, and recruitment effects in acute respiratory distress syndrome

BackgroundAcute lung injury and acute respiratory distress syndrome (ALI/ARDS) cause substantial morbidity and mortality despite improvements in the understanding of lung injury and advances in treatment. Recruitment maneuver (RM) with high sustained airway pressures is proposed as an adjunct to mechanical ventilation to maintain alveolar patency. In addition, RM has been advocated to improve pulmonary gas exchange. However, many factors may influence responses to RM and the effect of pleural effusion (PLE) is unknown. MethodThere were four groups in this study (n = 6 in each group). Group A was the control group, group B was the PLE group, group C was ARDS with RM, and group D was ARDS with PLE and RM. RM was performed in groups C and D, consisting of a peak pressure of 45 cm H2O with positive end-expiratory pressure of 35 cm H2O sustained for 1 min. Arterial blood gas, systemic and pulmonary hemodynamics, lung water, and respiratory mechanics were measured throughout. ResultAfter the induction of ALI/ARDS, there were significant decreases in partial pressure of oxygen in arterial blood, mean arterial pressure, systemic vascular resistance, and lung compliance. There were also significant increases in the alveolar–arterial O2 tension difference, partial pressure of arterial carbon dioxide, mean pulmonary arterial pressure, pulmonary vascular resistance, and lung water. The RM improved oxygenation, which was attenuated by PLE. ConclusionsALI/ARDS leads to poor oxygenation and hemodynamics. RM results in improved oxygenation, but this improvement is attenuated by PLE.

OUTCOME SCORING SYSTEMS FOR ACUTE RESPIRATORY DISTRESS SYNDROME

Acute respiratory distress syndrome (ARDS) is commonly diagnosed in intensive care units (ICUs), often in association with acute kidney injury. In this study, we compared the predictive value of outcome scoring systems: Acute Physiology and Chronic Health Evaluation IV (APACHE IV), earlier APACHE models, Sequential Organ Failure Assessment (SOFA), the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal failure (RIFLE) classification, and Acute Lung Injury score in critically ill patients with ARDS. We retrospectively abstracted data from the medical records of 135 critically ill ARDS patients in two medical ICUs of a tertiary care hospital from December 1999 to June 2006. Overall mortality rate was 65% (88/135). Forward conditional logistic regression identified APACHE IV, alveolar-arterial O2 tension difference, age, sepsis, and maximum RIFLE (RIFLEmax) score on ICU days 1 and 3 to be independent predictors of hospital mortality. The area under the receiver operating characteristic curve for the APACHE IV score revealed good fit (Hosmer and Lemeshow goodness-of-fit test results) and discriminative power (area under the receiver operating characteristic curve, 0.792 ± 0.038; P < 0.001). The cumulative survival rates at 6-month follow-up after hospital discharge were significantly (P < 0.001) different among ARDS patients with APACHE IV mortality rate 35% or less and APACHE IV mortality rate higher than 35%. The APACHE IV score and RIFLEmax score are predictors of hospital mortality in ARDS patients, with APACHE IV demonstrating desirable properties of prognostic accuracy.

Standard values and normal limits for arterial blood gases in healthy elderly Japanese subjects

We studied the standard values and normal limits for arterial blood gases in healthy elderly Japanese subjects. The criteria for inclusion were; 1) older than 60 years and able to walk independently, 2) non-smoker, 3) no respiratory symptoms, 4) no thoracic deformity, 5) no clinical signs of chest disease, 6) no abnormal findings in chest X ray, and 7) no cardiac disease or obesity. The number of subjects was 78. The oldest subject was a 96-year-old female. Arterial punctures were performed with the subjects in a recumbent position. PaO2 ranged from 79 to 106 Torr, with a mean value of 89.8 Torr. PaCO2 ranged from 32 to 48 Torr with a mean value of 39.6 Torr. Maximum values of alveolar-arterial O2 tension difference and arterial-alveolar N2 tension difference were 20.2 Torr and 11.6 Torr, respectively. The regression equation for PaO2 with respect to age was; PaO2 = 99.32-0.126 x (age), and its residual standard deviation was 6.06 Torr. These values were not different from those obtained in healthy young Japanese subjects.

Is pulmonary gas exchange during exercise in hypoxia impaired with the increase of cardiac output?

During exercise in humans, the alveolar-arterial O(2) tension difference ((A-a)DO(2)) increases with exercise intensity and is an important factor determining the absolute level of oxygen binding to hemoglobin and therefore the level of systemic oxygen transport. During exercise in hypoxia, the (A-a)DO(2) is accentuated. Using the multiple inert gas elimination technique it has been shown that during exercise in acute hypoxia the contribution of ventilation-perfusion inequality to (A-a)DO(2) is rather small and in the absence of pulmonary edema intrapulmonary shunts can be ruled out. This implies that the main mechanism limiting pulmonary gas exchange is diffusion limitation. It is presumed that an elevation of cardiac output during exercise in acute hypoxia should increase the (A-a)DO(2). However, no studies have examined how variations in cardiac output independently affect pulmonary diffusion with increases in exercise intensity. We have consistently observed that during steady-state, submaximal (100-120 W) exercise on the cycle ergometer in hypoxia the lung can accommodate an increase in cardiac output of approximately 2 L x min(-1) without any significant effect on pulmonary gas exchange. This result contrasts with the predicted effect of cardiac output on (A-a)DO(2) using the model of Piiper and Scheid, and thus indicates that an elevation of cardiac output is not necessarily accompanied by a reduction of mean transit time and (or) diffusion limitation during submaximal exercise in acute hypoxia. It remains to be determined what is the influence of changes in cardiac output per se on pulmonary gas exchange during high-intensity exercise.

Effects of Duration and Amount of Lung Stretch at Biophysical, Biochemical, Histological, and Transcriptional Levels in an In Vivo Rabbit Model of Mild Lung Injury

The purpose of this study was to characterize the effects of doubling minute ventilation (either by doubling ventilator frequency [Freq] or tidal volume [V T]) and of normal minute ventilation prolonged to 12-fold duration, synchronously at biophysical, biochemical/cellular, histological, and transcriptional levels in a model of mild lung injury. A prospective, randomized study was performed on adolescent New-Zealand white rabbits. The rabbits were randomly assigned to one of the following groups: control (normal minute ventilation for 0.5 hours); 1 x V T, 12-fold prolongation at normal V T (normal minute ventilation for 6 hours [12 x 0.5 hours]); 2 x Freq at normal V T (double minute ventilation for 6 hours); and 2 x V T at normal Freq (double minute ventilation for 6 hours). Normocapnia was maintained throughout the experiment. At the biophysical level, gas exchange (alveolar-arterial O2-tension difference [ AaDO2]) deteriorated by 23, 51, and 95%, and respiratory compliance decreased by 6.0, 18.4, and 26% in the 1 x V T, 2 x Freq, and 2 x V T group, respectively, during 6 hours of ventilation. Concomitantly, at the biochemical-cellular level, interleukin-8 (IL-8) in the bronchoalveolar lavage fluid increased 44-fold, 150-fold, and 275-fold ( P = 0.02), respectively. The white blood cell count decreased significantly in all three intervention groups. At the histological level, the influx of leukocytes as well as the tissue water content increased in proportion to the degree of injury. At the transcriptional level, lung IL-8 mRNA expression increased 11-fold in the 2 x V T group ( P = 0.002), 9-fold ( P = 0.02) in the 2 x Freq group, and 4-fold in the 1 x V T group as compared with control. Not only doubling V T, but also doubling Freq at normal V T injures the lung significantly, although to a lesser extent. A concept of weighted risk for increases of V T and Freq is proposed.

Comment on Point:Counterpoint “In health and in a normoxic environment, V̇o2 maxis/is not limited primarily by cardiac output and locomotor muscle blood flow”

Comment on Point:Counterpoint “In health and in a normoxic environment, V̇<scp>o</scp>_{2 max}is/is not limited primarily by cardiac output and locomotor muscle blood flow”

Evaluation of the Effects of Diabetes on Preoperative and Postoperative Patients' Status with Blood Glucose Level, Arterial Blood Gas, and Alveolar-arterial O2 Tension Difference

Background: Diabetes mellitus is the most common endocrinopathy encountered in the perioperative period. It is a disease of glucose dysregulation and carbohydrate intolerance frequently associated with acute and long-term systemic consequences, which may significantly impact morbidity and mortality. This study was performed to evaluate the effects of diabetes on perioperative patients’ status. Methods: Thirty adults patients, 15 control and 15 diabetic patients, who underwent upper abdominal surgery with general anesthesia were included in this study. We investigated blood glucose levels, arterial blood gas, blood chemistry values, and calculated alveolar- arterial oxygen tension differences. Statistical analyses were performed using the Fisher's exact test, unpaired t-test, paired t-test, and repeated measure ANOVA. Data are expressed as mean SD. Results: The blood glucose levels were significantly higher in the diabetic group than the control group during operation. The postoperative calcium and albumin concentrations were significantly lower in the diabetic patients than the control patients. The alveolar-arterial oxygen tension differences were significantly increased in the diabetic group compared with the control group during operation. Conclusions: This study demonstrated that the blood glucose levels were significantly increased in the diabetic patients compared with the control patients during operation. This finding suggests that blood glucose levels should be monitored and controlled within an adequate range in diabetic patients perioperatively.

Pulmonary interstitial edema in the pig after heavy exercise.

During exercise (especially in hypoxia), the alveolar-arterial O2 tension difference increases. This impairment of pulmonary gas exchange is caused partly by diffusion disequilibrium, but it has also been shown that an exercise-induced increase in ventilation-perfusion (VA/Q) inequality develops. Possible explanations of increased VA/Q mismatch include nonuniform pulmonary vasoconstriction, reduced gas mixing in the large airways, airway obstruction, and the development of interstitial pulmonary edema. To directly determine whether the latter develops in high-intensity short-term exercise, we exercised pigs on a motor-driven treadmill at the highest speed that they could sustain for 6-7 min. Heart rate reached 274 +/- 5 min-1 in the exercised group, confirming that the pigs reached a near-maximal level of exercise. While running, the pigs were killed by an intravenous overdose of pentobarbital. Postmortem, the lungs were immediately removed, drained of blood, weighed, and then airway fixed with 10% formaldehyde. Four tissue blocks of the right lung of each pig were taken from the ventral and dorsal areas of the upper and lower lobes, respectively. They were stained with hematoxylin and eosin and prepared for histological examination by light microscopy. There was no difference in the lung-to-body weight ratio between exercised pigs (7.72 +/- 0.87 g/kg) and a nonexercised control group (7.70 +/- 0.68 g/kg). However, we found a significantly higher percentage of pulmonary arteries with perivascular edema in exercised (33.8 +/- 3.4%) than in nonexercised pigs (20.0 +/- 4.0%; P < 0.02). Thus, perivascular edema (and thus possibly also parenchymal interstitial edema) can occur during short-term heavy exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Elastic Loading and Exercise on Pulmonary Gas Exchange in Dogs.

We assessed the effects of negative intrathoracic pressure induced by inspiratory elastic loading on pulmonary, gas exchange with and without electrically induced hindlimb exercise in 8 normal, anesthetized dogs. Two elastic loads (EL) were used; one of 81 and one of 140 cmH2O/liter. These are equivalent to doubling and tripling the normal elastance of the dog's respiratory system, respectively. Elastic loading decreased ventilation and caused hypoxemia and hypercapnia, but it did not affect systemic arterial pressure or heart rate. During exercise, increase in ventilation was limited, whereas increase in cardiac output was not affected by elastic loading. Alveolar-arterial O2 tension difference (A-aDO2) was not changed significantly by exercise alone. However, elastic loading accompanied by exercise increased A-aDO2. Although comparable end-inspiratory pleural pressure was achieved with large EL (-29 +/- 2 cmH2O, mean +/- SE) and small EL with exercise (-30 +/- 2 cmH2O), the latter increased A-aDO2 whereas the former did not. Large negative intrapleural pressure combined with increased cardiac output may have caused transient interstitial edema.

Gas exchange abnormalities after pneumonectomy in conditioned foxhounds

Loss of a major portion of lung tissue has been associated with impaired exercise capacity, but the underlying mechanisms are not well defined. We studied the alterations in gas exchange during exercise before and after left pneumonectomy in three conditioned foxhounds. After pneumonectomy, minute ventilation and O2 consumption at comparable submaximal work loads were unchanged but arterial PCO2 at any work load was higher, implying that ventilatory response to CO2 was impaired. Arterial hypoxemia and an elevated alveolar-arterial O2 tension difference (AaDO2) developed during heavy exercise. Using the multiple inert gas elimination technique, we determined the distributions of ventilation-perfusion (VA/Q) ratios postpneumonectomy. Significant increase in VA/Q inequality developed during exercise while the foxhounds were breathing room air, accounting for an average of 42% of the total increase in AaDO2 while diffusion limitation accounted for 58%. While the animals were breathing hypoxic gas mixture, diffusion limitation accounted for an average of 88% of the total increase AaDO2. Cardiac output and O2 delivery were reduced at a given O2 consumption after pneumonectomy. After pneumonectomy, the animals reached O2 consumptions close to the maximum expected for normal dogs. Compensation for the impairment in O2 delivery post-pneumonectomy occurred mainly by an increase in hemoglobin concentration. Training probably played an important role in returning exercise capacity toward prepneumonectomy levels. We conclude that significant abnormalities in gas exchange develop during exercise after loss of 42% of lung tissue, but the animals demonstrate a remarkable ability to compensate for these changes.

Severe Asthma

Asthmatic patients during sympton-free periods almost invariably have abnormalities in lung mechanics and gas exchange. Tentacious secretions and mucosal thickening exaggerate maldistribution of ventilation and cause flow limitation in small airways. Hence, the maximal expiratory flow volume loop in these patients will show impaired flow rates at low lung volumes and many will show a widened alveolar-arterial O2 tension difference. Preventive treatment should be aimed at reversing these abnormalities. The regular use of inhaled sympathomimetics and oral theophylline preparations is justified in the symptom-free patient whose history suggests that he is susceptible to acute exacerbations. Such patients commonly experience an improved sense of well-being, increased exercise tolerance, and a decrease in the frequency and severity of their acute episodes.

Reversible respiratory disease in beryllium workers.

A medical and environmental survey was carried out in a beryllium extraction and processing plant in 1971, and a follow-up study was done in 1974. Peak air concentrations of beryllium of as much as 50 times the accepted peak limit value were found in the plant in 1971. Radiographic changes of interstitial disease were found in 31 workers, hypoxemia was found in 20, and in 11 workers a combination of hypoxemia and radiographic changes of interstitial disease was seen. Follow-up in 1974 showed that air concentrations had all decreased significantly, mainly because of improvements in engineering and ventilation in the plant. Improvement in hypoxemia and decreased alveolar-arterial O2 tension difference at rest ([A-a]DO2) were noted in 13 of the 20 men who had hypoxemia in 1971 and were available for follow-up. In addition, radiographic abnormalities of interstitial disease were reversed in some workers. Our results suggest that improvement in gas exchange and radiographic findings of interstitial disease occurs when peak air concentrations of beryllium are decreased. Our approach in combining environmental and medical screening in workers exposed to beryllium enabled us to identify persons with early changes, to detect reversible abnormalities, and to correlate air concentrations with the medical status of workers.

Perfusion characteristics during cardiopulmonary bypass and subsequent changes in alveolar-arterial oxygen tension gradients.

In 11 elective coronary artery bypass graft (CABG) recipients, changes in alveolar-arterial O2 tension difference (deltaAaDO2) from 5 minutes before to 30 minutes after cardiopulmonary bypass (CPB) ranged from -54.9 to +63.1 torr and exhibited significant linear correlation (r = 0.77, p less than 0.01) with the mean arterial perfusion pressure (MAPP) during CPB multiplied by the duration (T) of CPB divided by the body surface area (BSA) of the patient. The regression equation (deltaAaDO2 = 0.015 MAPP divided by BSA X T -50) enables estimation of the delta AaDO2 to result from a given episode of CPB. Mural edema of airways and pulmonary vasculature, developing during CPB, may be a mechanism underlying this correlation.

Factors affecting A-aDo2 after open-heart surgery.

Intrapulmonary shunt, cardiac output, and O2 consumption as factors contributing to alveolar-arterial O2 tension difference (A-aDo2) were tested in 11 patients after open-heart surgery. A-aDo2 was well correlated with intrapulmonary shunt, as expected, but no correlation was found between cardiac index (CI) and intrapulmonary shunt. When total shunt (venous admixture) was above 11%, there was an inverse correlation between A-aDo2 and CI, and it was observed that CI falling below 2.5 L/min/sq m contributed significantly to the enlargement of A-aDo2. Low Pao2 (less than 65 torr, breathing air) was characterized by larger arterial-mixed venous O2 content difference than high Pao2 (is greater than 65 torr, on room air), indicating that A-aDo2 was influenced by cardiac output relative to metabolic demand. Intrapulmonary shunt played a main role in increasing A-aDo2 after open-heart surgery, and systemic factors, including changes in cardiac output and O2 consumption, also contributed to development of hypoxia.

Effect of altitude relocations upon AaDo2 at rest and during exercise.

The supine pulmonary venous admixture (shunt) has been measured at Cerro de Pasco, 4,350 m altitude in eight subjects native to high altitude (HAN) under resting condition. Alveolar-arterial O2 tension difference (AaDO2) was also determined at rest and during exercise. The same subjects were studied again after 10 days' sojourn at sea level in Lima at 150 m altitude. They were compared with four subjects from sea level (SLN) who were studied first at Lima and after 2 and 10 days at Cerro de Pasco. At altitude, AaDO2 was smaller in HAN than SLN both at rest and during exercise. Shunt was the same in both groups. It is concluded that HAN show more even ventilation/perfusion relationship (VA/Q) at altitude, probably due to their high pulmonary artery pressure. On the contrary, SLN show less even VA/Q on altitude exposure, since their shunt decreased 37%. At sea level, HAN increased their AaDO2 due partially to an increase of 110% in their shunt, and in part due to less even VA/Q as shown by augmented VD/VT ratios. Each group tended to have a more effective gas exchange in its own environment.

CONTINUOUS NEGATIVE CHEST WALL PRESSURE IN HYALINE MEMBRANE DISEASE: ONE YEAR EXPERIENCE

Application of a continuous positive transpulmonary pressure by producing a continuous negative chest wall pressure (CNP) was utilized in the treatment of 49 infants with severe hyaline membrane disease (HMD). In 23 infants in whom spontaneous alveolar ventilation was adequate, CNP was associated with an average elevation in arterial Po2 of over 40 mm Hg while inspired oxygen concentration remained unchanged. Alveolar-arterial O2 tension difference (A-aDo2) decreased significantly. All of these infants survived. In 26 infants with severe alveolar hypoventilation, CNP was used in conjunction with artificial ventilation. Arterial Po2 increased significantly and A-aDo2 decreased. Twelve of these infants survived (46%). The overall survival rate was 71.5%. CNP appears to be an important adjunct to the therapy of severe HMD.

VENTILATION AND RESPIRATORY GAS TRANSFER OF INFANTS WITH INCREASED PULMONARY BLOOD FLOW

Ventilation and respiratory gas transfer was studied in 44 infants; 13 of whom had pulmonary overperfusion without pulmonary edema or transposed great arteries. In order to assess the evenness of ventilation/perfusion ratios throughout the lung, (VA/Q distribution) measurements were made of the urine-alveolar nitrogen tension difference (U-Ā)DN2 in a separate group of six normal children and seven children with pulmonary overperfusion. Infants with pulmonary overperfusion (left-to-right shunts) had normal alveolar ventilation (149.6±18.2 ml/minute/kg). Respiratory rate (38.1±10.2) was slightly increased and tidal volume (6.0±1.3 ml/kg) was diminished, possibly due to reduced lung compliance. Measurements of dead space, dead space/tidal volume ratio, and alveolar ventilation/oxygen consumption ratio were unremarkable. No significant arterial-alveolar CO2 difference was detected in either normal subjects or those with heart disease, but a significantly increased alveolar-arterial O2 tension difference (A-a)DO2 of 22.4±8.6 mm Hg was found in infants with overperfused lungs. Measurements of (A-a)DO2 during 100% oxygen breathing and measurements of (U-Ā)DN2 in the air-breathing subjects both suggested that intrapulmonary venous admixture rather than VA/Q unevenness was the principal factor causing lowered oxygen tensions in the arterial blood of infants with overperfused lungs. Lowered arterial oxygen tension was associated with only trivial arterial unsaturation (92.8±2.4%) due to the high affinity of hemoglobin for oxygen.

Variation in alveolar-arterial O2 tension difference at high levels of alveolar O2 tension.

Variation in alveolar-arterial O2 tension difference at high levels of alveolar O2 tension.

STUDY OF ALVEOLAR FUNCTION IN PATIENTS OF FAR-ADVANCED PULMONARY TUBERCULOSIS (Particularly, Determination of Uneffective Ventilation Rate and Uneffective PuImonary Blood Flow Rate)

Alveolar function, particularly the ventilation-perfusion relationship with the determination of the ineffective ventilation rate and the ineffective pulmonary blood flow rate, was studied in 11 normal human beings and in 60 patients of F-A pulmonary tuberculosis, classified as Fibro0cavitary group, Diffuse Miliary and Nodular group and Diffuse Exudative group. The uneffecive wnfilation rate and uneffecive pulmonary blood flow rate were determined by the ratio of respiratory dead space to tidal volume and the ratio of venous admixture to cardiac output, respectively. The following results were obtained. 1.2. The tidal volume and respiratory dead space were significantly elevated not only in resting state but also in exercise in these patients with F-A pulm. tuberculosis. The large increase in the ratio of dead space to tidal volume observed in those patients with F-A pulm. tuberculosis and the reason was primarily an increase in respiratory dead space even in resting state. 3. 4.Slight reduction of the ratio of dead space to didal volume in exercise compared with resting state was observed in all groups, even in normal group. This was primarily due to large in crease of tidal volume compared with the increase of dead space in exercise. 5. The elevation of ineffective ventilation rate ineffective pulmonary blood flow rate mean 1.16 times of the load in ventilatory work and 1.26 times of load in pulmonary circulatory work are compelled in these patients with F-A pul. tuberculosis compared with normal group in resting state. 6. The alveolar arterial O2 tension difference and the ineffective pulmonary blood flow rate in resting and exercise were significantly elevated to mean value of 37.7 mmHg and 24% respectively in these patients with F-A pulm. tuberculosis, suggesting the increase of venous admixture. 7. No significant difference of ineffective pulmonary blood flow rate and A-a gradient were observed between each group of F-A pulm. tuberculosis except of slight increase in military and medular group. 8. Evidence of impaired oxygenation was present in all group of F-A pulm. tuberculosis even in resting state. 9. The elevation of ineffective pulmonary blood flow rate was associated with the elevation of uneffective ventilation rate in all groups of F-A pulm. tuberculosis. The load was more significant in circulatory work than ventilatory work. This means the impairment of distribution of alveolar ventilation was more significant than impairment of pulmonary vascular bed.