Effect of chestwall removal on expiratory flow in dogs.

We studied the effect of chestwall removal on Flow-Volume (F-V) curves in anesthetized dogs, by applying suction at the airway opening. Pressure and volume ranges utilized were comparable to those by others in the past for studies of expiratory flow in canine models. It was found: 1) Expiratory flow became nil at residual volume (RV) in the intact animal. On the contrary, flow after chestwall removal continued below RV, until the lung reached its minimal volume (Vmin) which averaged 11 +/- 6% TLC or 50% RV. 2) At high lung volumes, flow, particularly peak flow of F-V curves, was greater before than after chestwall removal. Thus the chestwall has a bimodal effect on flow. At low lung volumes, particularly below RV, the chestwall inhibits expiratory flow, and chestwall removal always results in flow increase, such that the lung can empty until all airways are collapsed, down to a volume of about 50% RV. On the contrary, the chestwall facilitates expiratory flow at high lung volumes, particularly at peak flow. The bimodality of chestwall effect on expiratory flow is consistent with the well known directional reversal of chestwall elastic recoil as volume changes, being nil at chestwall resting volume (Vcwr), and directing inwards (thus helping expiration) above Vcwr, or outwards (thus inhibiting expiration) below this volume (12). In a hypothetical situation of no chestwall resistance, chestwall effect on flow would be nil at Vcwr. In our experimentation, we found that the volume where the chestwall had no effect on expiratory flow averaged 71% TLC, clearly higher than Vcwr (49% TLC). We attribute the difference to the chestwall resistance.

Relationships between minute ventilation, oxygen uptake, and time during incremental exercise.

It has recently been reported that blood and muscle lactate increased exponentially during incremental exercise, casting some doubt upon the concept of 'anaerobic threshold'. To gain further insight into this controversy, we examined the relationships between minute ventilation (VE), time and oxygen uptake (VO2) in normal subjects during incremental exercise. During exercise, the relationship of VE to either time of exercise or to VO2 appeared curvilinear; VE was reliably described as an exponential function (y = axb + c) of both time of exercise (r2 = 0.96) and VO2 (r2 = 0.92). We also compared variables from 30-second incremental tests with variables obtained from quasi-steady-state incremental tests using cycle and treadmill ergometry. With the exception of heart rate, variables measured at maximum exercise were similar during short-duration and quasi-steady-state incremental tests. These data support the ideas that: there is no abrupt change in metabolism and oxygen availability during progressive exercise, and results of rapid incremental and quasi-steady-state exercise tests are generally comparable in normal individuals.

Supine change in arterial oxygenation in patients with chronic obstructive pulmonary disease.

In normal subjects, recumbent PaO2 differs from upright PaO2 as a function of the relationship between FRC and closing volume. However, in patients with lung disease, the factors controlling PaO2 change. Furthermore, the distribution of airway closure does not strictly reflect gravitational gradients in pleural pressure. Hence, we evaluated the effects of recumbency on PaO2 in patients with advanced COPD. We conducted pulmonary function tests and measured PaO2, AaPO2, change from upright to supine FRC, VE, cardiac output (QT), and mixed venous oxygen saturation (SvO2). Eight patients with COPD in whom PaO2 decreased in the supine position (Group I) were compared with 8 patients with COPD in whom PaO2 improved in the recumbent position (Group II); the only anthropometric difference between the groups was greater body weight in Group II (p less than 0.05). Pulmonary function was comparable in the 2 groups. In both groups, FRC decreased with recumbency, but supine FRC and delta FRC did not differ between groups nor correlate significantly with PaO2, AaPO2, or venous admixture (QVA/QT). Supine SVO2 increased in both groups, but supine QT increased significantly only in Group I. In Group II, recumbent QVA/QT did not change significantly, whereas recumbent QVA/QT increased (p less than 0.02) in Group I. The cause for increased QVA/QT in Group I was reduced VE plus increased QT while supine; in contrast, by maintaining a higher supine VE and by not increasing QT significantly, an increase in QVA/QT was prevented in Group II subjects, an increase that would otherwise have overwhelmed the benefits of increased recumbent SVO2 on PaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hydralazine on hemodynamics, ventilation, and gas exchange in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

Reports on hemodynamic effects of hydralazine on pulmonary hypertension (primary or secondary) usually include cases with severe disease or with mixed varieties of pulmonary vascular disease. Serious side effects and death have been reported. Effects of this drug on ventilation and gas exchange are unknown. We investigated the short-term effects of hydralazine treatment on hemodynamics, ventilation, and gas exchange in a relatively homogeneous group of patients with severe chronic obstructive pulmonary disease and moderate exertional pulmonary hypertension (mean pulmonary artery pressure, 43 +/- 3 mmHg). Hydralazine produced significant improvement in cardiac index, total pulmonary resistance, and oxygen transport. We also observed significant improvement in alveolar ventilation (mean PaCO2, decreased from 47 +/- 2 to 40 +/- 3 mmHg at rest and from 51 +/- 3 to 43 +/- 3 mmHg during exercise). The severe exertional hypoxemia of the group (mean PaO2, 48 +/- 2 mmHg) improved significantly (mean PaO2, 57 +/- 3 mmHg). Four of 11 patients showed increased exercise tolerance after hydralazine. This change is probably related to a combined improvement in hemodynamics plus a newly observed improvement in gas exchange and ventilation. Three of 14 patients could not tolerate hydralazine because of marked tachycardia. Serious side effects were not observed in the remaining group.

A comparison of incremental exercise tests during cycle and treadmill ergometry.

We evaluated a short-duration maximum exercise test by comparing a 15-s incremental exercise protocol with a 1-min incremental method. Twenty normal men and women were studied using cycle and/or treadmill ergometry. In subjects tested on both exercise devices, anaerobic threshold and maximal oxygen uptake (VO2max) were higher for both protocols on the treadmill than on the cycle ergometer (P less than 0.001). However, when the 15-s and 1-min tests were compared using the same device (treadmill or cycle), there were no significant differences between protocols in anaerobic threshold or maximum exercise values of minute ventilation, respiratory rate, tidal volume, VO2max, oxygen pulse, and peak expiratory flow rate. Linear regression analyses indicated differences between the 15-s and 1-min protocols when cardiopulmonary measurements were related to power; however, the two protocols were comparable when cardiopulmonary data were related to oxygen uptake. Comparisons between protocols or between exercise devices were not systematically different in large vs small individuals, or in men vs women. Short-duration incremental exercise tests appear to be reliable, practical methods for assessing exercise performance in normal individuals.

Gas exchange in nonperfused dog lungs.

Gas exchange was studied under conditions of zero perfusion both in situ and in vitro. Six dogs, anesthetized with pentobarbital sodium, underwent surgical interruption of both pulmonary and bronchial circulations to the left lung. Despite the absence of perfusion, O2 uptake for the left lung ranged from 0.76 to 0.98 ml/min, whereas CO2 elimination greatly exceeded O2 uptake ranging from 1.68 to 4.34 ml/min. In addition, CO2 output was observed to vary directly with the level of minute ventilation (VE) and inversely with end-tidal CO2 concentration. To investigate the mechanisms responsible for these findings we studied 20 excised, ventilated, but nonperfused dog lungs to evaluate the relative roles of tissue metabolism and transpleural diffusion to gas exchange. The results obtained with these excised lungs under conditions of varying VE and extrapleural gas concentrations indicate that the high respiratory exchange ratios observed in situ can be explained by the greater rate with which CO2 diffuses through the pleura, and that reduced ventilation decreases total gas transfer by decreasing the transpleural partial pressure driving gradient. Our data further document that the concentration of CO2 in alveolar gas may differ significantly from that present in inspired gas under conditions of ventilation-perfusion ratio equal to infinity, and that tissue metabolism as well as transpleural diffusion contribute to gas exchange in nonperfused lung.

Mixed venous oxygenation, exercise, body posture, and v/q ratio in chronic obstructive pulmonary disease.

Mixed venous oxygenation (partial pressure, PVO2; saturation, SVO2) and its impact on pulmonary function at rest in the supine position (SUP), at rest in the standing position (STAND), and during maximal treadmill exercise (Emax), were studied in 41 stable patients with chronic obstructive pulmonary disease, using arterial and right heart (Swan-Ganz) catheterization. The patients represented a broad spectrum of disease severity (VC, 3.1 +/- 0.9 L; FEF 25-75, 1.0 +/- 0.7 L). It was found that: (a) venous oxygenation was uniform among different patients in the supine position at rest (PVO2, 33.8 +/- 2.4 mmHg' SVO2, 76.2 +/- 3.6%), regardless of the heterogeneity in airway obstruction, as previously reported by others; (b) venous oxygenation was also uniform in STAND (PVO2, 29.5 +/- 2.5 mmHg; SVO2, 58 +/- 3.9%) and treadmill Emax (PVO2, 22.4 +/- 3.3 mmHg; SVO2, 34.4 +/- 6%), an observation not previously reported; (c) the orthostatic mixed venous desaturation at rest was pronounced, and was nearly as great as that from STAND to Emax; (d) the potential effect of mixed venous desaturation on alveolar O2 partial pressure (PAO2) and end-capillary O2 saturation (SCO2) was not obvious from SUP to STAND, and from STAND to Emax conditions, being masked by an appropriate increase in overall V/Q ratio; (e) because of constant SCO2 and low interindividual variations of SVO2, there was a high correlation of arterial saturation (SaO2) to venous admixture (Qva/Qt, sum of true shunt and shuntlike components) for each of the conditions studied. Hence, because of high correlation of the equations relating SaO2 to Qva/Qt (r greater than 0.9), these relationships might be used for noninvasive prediction of Qva/Qt from SaO2 in patients with COPD.

Pleural paragonimiasis in a Southeast Asia refugee.

We report a Laotian patient with pleural paragonimiasis who did not have the usual diagnostic triad for this parasitic disease. He did not have chronic hemoptysis (considered by many to be an "invariable" finding), there were no pulmonary infiltrations, and stool and sputum examinations did not yield Paragonimus ova. The diagnosis was made on the basis of ova found in the pleural fluid. Paragonimiasis pleural effusion did not resolve with bithionol, the drug of choice for pulmonary paragonimiasis, and, as a result, chest tube drainage was required. The difference between pleural paragonimiasis and pulmonary paragonimiasis is that the classic clinical presentation of the latter (hemoptysis, ova in sputum and stools, lung infiltration, etc.) requires an intrapulmonary location on the parasite. A search for ova in the pleural fluid may be the only diagnostic tool for patients suspected of pleural paragonimiasis. With the influx of Southeast Asia refugees, this case report may be of relevance to U.S. physicians involved in the care of patients in whom not all chronic pleuropulmonary diseases are tuberculous.

Observations on pleural fluid pressures as fluid is withdrawn during thoracentesis.

In 52 patients with pleural effusions, pleural pressures were measured initially and serially as pleural fluid was withdrawn. Pleural fluid aspiration was continued until the pleural pressure fell below -20 cmH2O, or the patient developed excessive symptoms, or no more fluid could be obtained. The initial pleural pressure ranged from +8 to -21 cmH2O. The rate of pleural pressure change as fluid was withdrawn was highly variable. In 13 of 52 procedures (25%), thoracentesis was terminated because the pressure fell below -20 cmH2O. Negative initial pleural pressures and/or rapid changes in the pressures as fluid was withdrawn were suggestive of malignancy or trapped lung. The measurement of pleural pressures in patients with pleural effusions may be useful diagnostically. More importantly, because large changes in pleural pressures are not readily detectable by the operator, pleural pressures should be monitored when large amounts (> 1,000 ml) of pleural fluid are removed to increase the safety of the procedure.

Hypoxemia during exercise in patients with chronic obstructive pulmonary disease.

Arterial oxygenation at rest and during maximal treadmill exercise was studied in a group of 17 patients with chronic obstructive pulmonary disease. Patients who developed exertional hypoxemia (subgroup 1) were compared to others who did not (subgroup 2). There was no significant difference between the 2 subgroups at rest in terms of mixed venous PO2, cardiac output, or venous admixture. Subgroup 1 had more severe respiratory impairment than subgroup 2, but there was marked overlap of their respective lung volumes and flows. Both subgroups showed the same extent of desaturation of mixed venous blood during maximal treadmill exercise, so that exertional hypoxemia cannot be explained on the basis of low mixed venous O2. The marked difference between subgroup 1 and subgroup 2 was that the latter showed decreased venous admixture on exercise. Because of the relative constancy of mixed venous blood desaturation, arterial saturation was closely correlated with venous admixture both at rest (r = 0.931) and during exercise (r = 0.985).

Immersion vs pressure-breathing and diaphragmatic function in the upright position.

In seven anesthetized dogs, immersion in the upright position to mid-neck level (IM) was compared to pressure breathing (PB) under dry conditions during constant-stimulus diaphragmatic contraction (EPS). The comparison was in terms of EPS-induced changes in alveolar pressure under static condition (Pmus); EPS-induced tidal volume (VT); and the VT/Pmus ratio (C'). It was found that at iso-lung volume (V): (a) Pmus was greater in IM than in PB, the difference increased at higher V; (b) VT was greater in IM than in PB, but the VT difference (deltaVT) did not parallel that in Pmus; VT was maximum at a V equal to approximately 90% of FRC in air (FRCd) and decreased below and above this volume; (c) during both IM and PB, the VT-V relationship reflected a biphasic relationship of C' to V and appeared to be inherent to the upright position.

A single-breath method of alveolar O2 determination.

We designed a single-breath method of alveolar O2 determination, requiring only a single tidal breath expirate and concomitant arterial blood sample. The PAO2 equation used in our method was derived by applying the Bohr equation to both O2 and CO2 and independant of VO2, VCO2 and RQ. In 35 patients with different degrees of airway obstruction, at rest and during exercise, the single-breath method agreed well with the classic method of PAO2 determination which required 3 min of expired gas collection and derivation of VO2, VCO2 and RQ. The mean difference between the PAO2 estimates by the two methods was 0.36 mm Hg as calculated for all patients, both at rest and during exercise. At rest, in 2 out of 35 cases the difference was greater than 2 mm Hg and such difference happened only in 1 case during exercise. A good correlation existed between the two PAO2 estimates by the two methods (r ranging from 0.977 to 0.996). The data indicated that single-breath method of PAO2 determination was reliable. Its extreme simplicity would facilitate greatly the assessment of gas exchange efficiency in situations where both patient's cooperation and laborator equipment are less than optimum.

Functional residual capacity and body position in the dog.

Resting lung volumes in the supine position (FRCs) were determined by N2 washout method in 67 dogs under pentobarbital anesthesia and computed in ml/kg body weight (BW). In 21 other dogs, FRCs and the change in FRC from the supine to upright positions (deltaFRC) were determined; these lung volumes were expressed in ml/kg BW and in percentage of TLC40 (lung volume at 40 cmH2O positive-pressure inflation). It was found that a) FRCs averaged 38.6 plus or minus 8.2 and 42 plus or minus 5.9 ml/kg BW in the two groups of dogs; b) deltaFRC averaged 23 plus or minus 4 ml/kg BW resulted in large data dispersion, a large coefficient of variation (CV) and a poor correlation (r) of lung volume to BW; D) on the contrary, marked uniformity of FRCs and FRCu (upright FRC) was obtained by expressing the resting lung volumes in %TLC40, allowing an accurate prediction of FRC from the inspiratory capacity (IC). Relationship of FRCu to TLC was comparable to human data reported in the literature. FRCs (%TLC40) was smaller than values previously reported for awake human subjects, probably due to the FRCs reduction in our dogs by anesthesia.

Diaphragmatic function during immersion.

Diaphragmatic function during immersion to midneck level was studied in upright mongrel dogs, using constant electrophrenic stimulation. Effectiveness of diaphragmatic contraction was analyzed in terms of inspired volume (VT) (with airways open), and change in intrathoracic pressure (Pmus) (with the respiratory system occluded). Hydrostatic compression of the immersed body decreased functional residual capacity (FRC) to 55% base-line value (FRCO), resulting in a 2.8-fold increase in Pmus. In spite of this Pmus increase, VT often decreased during immersion, averaging only 83% VTO (base-line value in air). Hence, immersion was associated with a marked stiffening of the respiratory system. The Pmus increase during immersion persisted after restoration of FRC to FRCO, and was related to diaphragmatic length being greater in water than in air under condition of iso-lung volume. In all, there were three factors affecting diaphragmatic function during immersion: FRC reduction, change in thoracic configuration, and stiffening of the respiratory system.

133Xenon washout patterns during diaphragmatic breathing. Studies in normal subjects and patients with chronic obstructive pulmonary disease.

Studies of the washout of radioactive 133xenon were performed in six normal subjects and six patients with chronic obstructive pulmonary disease during normal and diaphragmatic breathing. Subjects were unable to change the distribution of ventilation with diaphragmatic breathing. In all normal subjects and in three of the six subjects with chronic obstructive pulmonary disease, overall washout improved with diaphragmatic breathing. It is suggested that this change was related to the slower, deeper tidal volumes used by these subjects during diaphragmatic breathing.

Cervical accessory respiratory muscle function in a patient with a high cervical cord lesion.

The function of the accessory respiratory muscles (ARM) of the neck were studied in a quadriplegic patient suffering from a C2-3 lesion of the cervical spinal cord. Subtotal expiratory paralysis resulted in an essentially complete loss of expiratory reserve volume such that residual volume and functiona residual capacity were equal (RV=FRC). Tidal volume and vital capacity were severely reduced. Being extrinsic to the chest, the ARM of the neck functioned independently of changes in thoracic gas volume; however, their performance appeared posture-dependent, and was less efficient in the sitting position. Despite the fact that the ARM preferentially expanded the upper part of the ribcage, significant V/Q mismatch did not seem to occur. Voluntary use of glossopharynegeal breathing (GPB) greatly enhanced the patient's ventilatory capability. Flow volume data during GPB documented the efficiency of the glossopharyngeal muscles, which function as a positive pressure pump to force air into the lungs.