VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema.

Ventilation-perfusion (VA/Q) inequality has been shown to increase with exercise. Potential mechanisms for this increase include nonuniform pulmonary vasoconstriction, ventilatory time constant inequality, reduced large airway gas mixing, and development of interstitial pulmonary edema. We hypothesized that persistence of VA/Q mismatch after ventilation and cardiac output subside during recovery would be consistent with edema; however, rapid resolution would suggest mechanisms related to changes in ventilation and blood flow per se. Thirteen healthy males performed near-maximal cycle ergometry at an inspiratory PO2 of 91 Torr (because hypoxia accentuates VA/Q mismatch on exercise). Cardiorespiratory variables and inert gas elimination patterns were measured at rest, during exercise, and between 2 and 30 min of recovery. Two profiles of VA/Q distribution behavior emerged during heavy exercise: in group 1 an increase in VA/Q mismatch (log SDQ of 0.35 +/- 0.02 at rest and 0.44 +/- 0.02 at exercise; P less than 0.05, n = 7) and in group 2 no change in VA/Q mismatch (n = 6). There were no differences in anthropometric data, work rate, O2 uptake, or ventilation during heavy exercise between groups. Group 1 demonstrated significantly greater VA/Q inequality, lower vital capacity, and higher forced expiratory flow at 25-75% of forced vital capacity for the first 20 min during recovery than group 2. Cardiac index was higher in group 1 both during heavy exercise and 4 and 6 min postexercise. However, both ventilation and cardiac output returned toward baseline values more rapidly than did VA/Q relationships. Arterial pH was lower in group 1 during exercise and recovery. We conclude that greater VA/Q inequality in group 1 and its persistence during recovery are consistent with the hypothesis that edema occurs and contributes to the increase in VA/Q inequality during exercise. This is supported by observation of greater blood flows and acidosis and, presumably therefore, higher pulmonary vascular pressures in such subjects.     

Ventilation-perfusion inequality during constant-flow ventilation

Previous work by Lehnert et al. (J. Appl. Physiol. 53:483-489, 1982) has demonstrated that adequate alveolar ventilation can be maintained during apnea in anesthetized dogs by delivering a continuous stream of inspired ventilation through cannulas aimed down the main-stem bronchi. Because an asymmetric distribution of ventilation might introduce ventilation-perfusion (VA/Q) inequality, we compared gas exchange efficiency in nine anesthetized and paralyzed dogs during constant-flow ventilation (CFV) and conventional ventilation (intermittent positive-pressure ventilation, IPPV). Gas exchange was assessed using the multiple inert gas elimination technique. During CFV at 3 l X kg-1 X min-1, lung volume, retention-excretion differences (R-E*) for low- and medium-solubility gases, and the log standard deviation of blood flow (log SD Q) increased, compared with the findings during IPPV. Reducing CFV flow rate to 1 l X kg-1 X min-1 at constant lung volume improved R-E* and log SD Q, but significant VA/Q inequality compared with that at IPPV remained and arterial PCO2 rose. Comparison of IPPV and CFV at the same mean lung volume showed a similar reversible deterioration in gas exchange efficiency during CFV. We conclude that CFV causes significant VA/Q inequality which may be due to nonuniform ventilation distribution and a redistribution of pulmonary blood flow.     

Effect of regional alveolar hypoxia on gas exchange in dogs

We studied the effects of left lower lobe (LLL) alveolar hypoxia on pulmonary gas exchange in anesthetized dogs using the multiple inert gas elimination technique (MIGET). The left upper lobe was removed, and a bronchial divider was placed. The right lung (RL) was continuously ventilated with 100% O2, and the LLL was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Whole lung and individual LLL and RL ventilation-perfusion (VA/Q) distributions were determined. LLL hypoxia reduced LLL blood flow and increased the perfusion-related indexes of VA/Q heterogeneity, such as the log standard deviation of the perfusion distribution (log SDQ), the retention component of the arterial-alveolar difference area [R(a-A)D], and the retention dispersion index (DISPR*) of the LLL. LLL hypoxia increased blood flow to the RL and reduced the VA/Q heterogeneity of the RL, indicated by significant reductions in log SDQ, R(a-A)D, and DISPR*. In contrast, LLL hypoxia had little effect on gas exchange of the lung when evaluated as a whole. We conclude that flow diversion induced by regional alveolar hypoxia preserves matching of ventilation to perfusion in the whole lung by increasing gas exchange heterogeneity of the hypoxic region and reducing heterogeneity in the normoxic lung.     

Ventilation-perfusion relationships in the lung during head-out water immersion.

Water immersion can cause airways closure during tidal breathing, and his may result in areas of low ventilation-perfusion (VA/Q) ratios (VA/Q less than or equal to 0.1) and/or shunt and, ultimately, hypoxemia. We studied this in 12 normal males: 6 young (Y; aged 20-29 yr) with closing volume (CV) less than expiratory reserve volume (ERV), and six older (O; aged 40-54 yr) with CV greater than ERV during seated head-out immersion. Arterial and expired inert gas concentrations and dye-dilution cardiac output (Q) were measured before and at 2, 5, 10, 15, and 20 min in 35 degrees C water. During immersion, Y showed increases in expired minute ventilation (VE; 8.3-10.3 l/min), Q (6.1-8.2 l/min), and arterial PO2 (PaO2; 91-98 Torr; P less than or equal to 0.05). However, O2 uptake (VO2), shunt, amount of low-VA/Q areas (% of Q), and the log standard deviation of the perfusion distribution (log SDQ) were unchanged. During immersion, O showed increases in shunt (0.6-1.8% of Q), VE (8.5-11.4 l/min), and VO2 (0.31-0.40 l/min) but showed no change in low-VA/Q areas, log SDQ, Q, or PaO2. Throughout, O showed more VA/Q inequality (greater log SDQ) than Y (O, 0.69 vs. Y, 0.47).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gas density dependence of regional VA/V and VA/Q inequality during constant-flow ventilation

Constant-flow ventilation (CFV) is achieved by delivering a constant stream of inspiratory gas through cannulas aimed down the main stem bronchi at flow rates totaling 1-3 l.kg-1.min-1 in the absence of tidal lung motion. Previous studies have shown that CFV can maintain a normal arterial PCO2, although significant ventilation-perfusion (VA/Q) inequality appears. This VA/Q mismatch could be due to regional differences in lung inflation that occur during CFV secondary to momentum transfer from the inflowing stream to resident gas in the lung. We tested the hypothesis that substitution of a gas with lower density might attenuate regional differences in alveolar pressure and reduce the VA/Q inequality during CFV. Gas exchange was studied in seven anesthetized dogs by the multiple inert gas elimination technique during ventilation with intermittent positive-pressure ventilation, CFV with O2-enriched nitrogen (CFV-N2), or CFV with O2-enriched helium (CFV-He). As an index of VA/Q inequality independent of shunt, the log SD blood flow increased from 0.757 +/- 0.272 during intermittent positive-pressure ventilation to 1.54 +/- 0.36 (P less than 0.001) during CFV-N2. Switching from CFV-N2 to CFV-He at the same flow rate did not improve log SD blood flow (1.45 +/- 0.21) (P greater than 0.05) but tended to increase arterial PCO2. In excised lungs with alveolar capsules attached to the pleural surface, CFV-He significantly reduced alveolar pressure differences among lobes compared with CFV-N2 as predicted. Regional alveolar washout of Ar after a stap change of inspired concentration was slower during CFV--He than during CFV-N2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spectral analysis of inert gas elimination data: resolution limits

A new method of analyzing inert gas data for recovery of the pulmonary ventilation-perfusion ration (VA/Q) distribution is proposed. It is shown that the conventional inert gas elimination equation takes the form of a convolution integral, and the relationship between VA/Q distribution and inert gas elimination resembles that of a noncausal low-pass filter with infinite zero-frequency gain. With the use of this formulation, characteristic features of VA/Q distribution may be represented in the frequency domain in terms of the corresponding energy spectrum. It is shown that the lack of resolution associated with finite data samples and measurement error is caused by distortions in the high-frequency contents of the resulting VA/Q distribution. With six inert gases, the technique cannot resolve a log SD less than 0.21 decade and a modal separation less than 0.87 decade. In the presence of measurement error, the degree of resolution is even less. It is suggested that for maximum resolution the number of discrete and duplicate data samples should be chosen so that the resulting noise and sampling cutoff frequencies are approximately equal.     

Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs.

The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2-3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model.     

Ventilation-perfusion inequality in normal humans during exercise at sea level and simulated altitude

To investigate the effects of both exercise and acute exposure to high altitude on ventilation-perfusion (VA/Q) relationships in the lungs, nine young men were studied at rest and at up to three different levels of exercise on a bicycle ergometer. Altitude was simulated in a hypobaric chamber with measurements made at sea level (mean barometric pressure = 755 Torr) and at simulated altitudes of 5,000 (632 Torr), 10,000 (523 Torr), and 15,000 ft (429 Torr). VA/Q distributions were estimated using the multiple inert gas elimination technique. Dispersion of the distributions of blood flow and ventilation were evaluated by both loge standard deviations (derived from the VA/Q 50-compartment lung model) and three new indices of dispersion that are derived directly from inert gas data. Both methods indicated a broadening of the distributions of blood flow and ventilation with increasing exercise at sea level, but the trend was of borderline statistical significance. There was no change in the resting distributions with altitude. However, with exercise at high altitude (10,000 and 15,000 ft) there was a significant increase in dispersion of blood flow (P less than 0.05) which implies an increase in intraregional inhomogeneity that more than counteracts the more uniform topographical distribution that occurs. Since breathing 100% O2 at 15,000 ft abolished the increased dispersion, the greater VA/Q mismatching seen during exercise at altitude may be related to pulmonary hypertension.     

Operation Everest II: pulmonary gas exchange during a simulated ascent of Mt. Everest

Eight normal subjects were decompressed to barometric pressure (PB) = 240 Torr over 40 days. The ventilation-perfusion (VA/Q) distribution was estimated at rest and during exercise [up to 80-90% maximal O2 uptake (VO2 max)] by the multiple inert gas elimination technique at sea level and PB = 428, 347, 282, and 240 Torr. The dispersion of the blood flow distribution increased by 64% from rest to 281 W, at both sea level and at PB = 428 Torr (heaviest exercise 215 W). At PB = 347 Torr, the increase was 79% (rest to 159 W); at PB = 282 Torr, the increase was 112% (108 W); and at PB = 240 Torr, the increase was 9% (60 W). There was no significant correlation between the dispersion and cardiac output, ventilation, or pulmonary arterial wedge pressure, but there was a correlation between the dispersion and mean pulmonary arterial pressure (r = 0.49, P = 0.02). When abnormal, the VA/Q pattern generally had perfusion in lung units of zero or near zero VA/Q combined with units of normal VA/Q. Alveolar-end-capillary diffusion limitation of O2 uptake (VO2) was observed at VO2 greater than 3 l/min at sea level, greater than 1-2 l/min VO2 at PB = 428 and 347 Torr, and at higher altitudes, at VO2 less than or equal to 1 l/min. These results show variable but increasing VA/Q mismatch with long-term exposure to both altitude and exercise. The VA/Q pattern and relationship to pulmonary arterial pressure are both compatible with alveolar interstitial edema as the primary cause of inequality.     

Pulmonary gas exchange in humans during exercise at sea level

Previous studies have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during exercise at simulated altitude and suggested that similar changes could occur even at sea level. We used the multiple-inert gas-elimination technique to further study gas exchange during exercise in healthy subjects at sea level. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate, minute ventilation, respiratory rate, and blood temperature were recorded at rest and during steady-state exercise in the following order: rest, minimal exercise (75 W), heavy exercise (300 W), heavy exercise breathing 100% O2, repeat rest, moderate exercise (225 W), and light exercise (150 W). Alveolar-to-arterial O2 tension difference increased linearly with O2 uptake (VO2) (6.1 Torr X min-1 X 1(-1) VO2). This could be fully explained by measured VA/Q inequality at mean VO2 less than 2.5 l X min-1. At higher VO2, the increase in alveolar-to-arterial O2 tension difference could not be explained by VA/Q inequality alone, suggesting the development of diffusion limitation. VA/Q inequality increased significantly during exercise (mean log SD of perfusion increased from 0.28 +/- 0.13 at rest to 0.58 +/- 0.30 at VO2 = 4.0 l X min-1, P less than 0.01). This increase was not reversed by 100% O2 breathing and appeared to persist at least transiently following exercise. These results confirm and extend the earlier suggestions (8, 21) of increasing VA/Q inequality and O2 diffusion limitation during heavy exercise at sea level in normal subjects and demonstrate that these changes are independent of the order of performance of exercise.     

Pulmonary gas exchange in humans exercising at sea level and simulated altitude

In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady-state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study.     

Effect of ventilation-perfusion inhomogeneity and N(2)O on oxygenation: physiological modeling of gas exchange.

Ventilation-perfusion (VA/Q) inhomogeneity was modeled to measure its effect on arterial oxygenation during maintenance-phase anesthesia involving an inspired mixture of 30% O(2) and either N(2)O or N(2). A multialveolar compartment computer model was constructed based on a log normal distribution of VA/Q inhomogeneity. Increasing the log SD of the distribution of blood flow from 0 to 1.75 produced a progressive fall in arterial PO(2) (Pa(O(2))). The fall was less steep in the presence of N(2)O than when N(2) was present instead. This was due mainly to the concentrating effect of N(2)O uptake on alveolar PO(2) in moderately low VA/Q compartments. The improvement in Pa(O(2)) when N(2)O was present instead of N(2) was greatest when the degree of VA/Q inhomogeneity was in the range typically seen in anesthetized patients. Models based on distributions of expired and inspired alveolar ventilation give quantitatively different results for Pa(O(2)). In the presence of VA/Q inhomogeneity, second-gas and concentrating effects may have clinically significant effects on arterial oxygenation even at "steady-state" levels of N(2)O uptake.     

Diffusion limitation in normal humans during exercise at sea level and simulated altitude

The relative roles of ventilation-perfusion (VA/Q) inequality, alveolar-capillary diffusion resistance, postpulmonary shunt, and gas phase diffusion limitation in determining arterial PO2 (PaO2) were assessed in nine normal unacclimatized men at rest and during bicycle exercise at sea level and three simulated altitudes (5,000, 10,000, and 15,000 ft; barometric pressures = 632, 523, and 429 Torr). We measured mixed expired and arterial inert and respiratory gases, minute ventilation, and cardiac output. Using the multiple inert gas elimination technique, PaO2 and the arterial O2 concentration expected from VA/Q inequality alone were compared with actual values, lower measured PaO2 indicating alveolar-capillary diffusion disequilibrium for O2. At sea level, alveolar-arterial PO2 differences were approximately 10 Torr at rest, increasing to approximately 20 Torr at a metabolic consumption of O2 (VO2) of 3 l/min. There was no evidence for diffusion disequilibrium, similar results being obtained at 5,000 ft. At 10 and 15,000 ft, resting alveolar-arterial PO2 difference was less than at sea level with no diffusion disequilibrium. During exercise, alveolar-arterial PO2 difference increased considerably more than expected from VA/Q mismatch alone. For example, at VO2 of 2.5 l/min at 10,000 ft, total alveolar-arterial PO2 difference was 30 Torr and that due to VA/Q mismatch alone was 15 Torr. At 15,000 ft and VO2 of 1.5 l/min, these values were 25 and 10 Torr, respectively. Expected and actual PaO2 agreed during 100% O2 breathing at 15,000 ft, excluding postpulmonary shunt as a cause of the larger alveolar-arterial O2 difference than accountable by inert gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism.

We studied the roles of endothelins in determining ventilation (Va) and perfusion (Q) mismatch in a porcine model of acute pulmonary thromboembolism (APTE), using a nonspecific endothelin antagonist, tezosentan. Nine anesthetized piglets (approximately 23 kg) received autologous clots (approximately 20 g) via a central venous catheter at time = 0 min. The distribution of Va and Q at five different time points (-30, -5, 30, 60, 120 min) was mapped by fluorescent microspheres of 10 different colors. Five piglets (group 1) received tezosentan (courtesy of Actelion) starting at time = 40 min for 2 h, and four piglets (group 2) received only saline and served as control. Our results showed that, in all of the animals at 30 min following APTE but before tezosentan, the mean Va/Q was increased, as was Va/Q heterogeneity (log SD Va/Q), which represented a widening of its main peak. Afterwards, tezosentan attenuated the pulmonary hypertension in group 1 but also produced moderate systemic hypotension. However, it did not improve arterial PO2 or Va/Q mismatch. We concluded that endothelin antagonism had minimal impact on gas exchange following APTE and confirmed our earlier observation that the main mechanism for hypoxemia in APTE was due to the mechanical redistribution of pulmonary regional blood flow away from the embolized vessels, resulting in the creation of many divergent low and high Va/Q regions.     

Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia.

The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial PO(2) (Pa(O(2)); 92.1 +/- 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in Pa(O(2)) (81.7 +/- 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O(2)). During normoxia at 90% peak O(2) consumption, Pa(O(2)) was lower in E compared with C (87 +/- 4 vs. 97 +/- 6 Torr, P < 0.001) and alveolar-to-arterial O(2) tension difference (A-aDO(2)) was greater (33 +/- 4 vs. 23 +/- 1 Torr, P < 0. 001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of the A-aDO(2) (P < 0.01). There were no significant differences between groups in arterial PCO(2) (Pa(CO(2))) or ventilation-perfusion (VA/Q) inequality as measured by the log SD of the perfusion distribution (logSD(Q)). Stepwise multiple linear regression revealed that lung O(2) diffusing capacity (DL(O(2))), logSD(Q), and Pa(CO(2)) each accounted for approximately 30% of the variance in Pa(O(2)) (r = 0.95, P < 0.001). These data suggest that EIH has a multifactorial etiology related to DL(O(2)), VA/Q inequality, and ventilation.     

Linear programming analysis of VA/Q distributions: limits on central moments

Linear programming examines the boundaries of infinite sets. We used this method with the multiple-inert gas-elimination technique to examine the central moments and arterial blood gases of the infinite family of ventilation perfusion (VA/Q) distributions that are compatible with a measured inert gas-retention set. A linear program was applied with Monte-Carlo error simulation to theoretical retention data, and 95% confidence intervals were constructed for the first three moments (mean, dispersion, and skew) and the arterial PO2 and PCO2 of all compatible blood flow distributions. Six typical cases were studied. Results demonstrate narrow confidence intervals for both the lower moments and predicted arterial blood gases of all test cases, which widen as moment number or error increase. We conclude that the blood gas composition and basic structure of all compatible VA/Q distributions are tightly constrained and that even subtle changes in this structure, as may occur experimentally, can be identified.     

Conebulization of surfactant and urokinase restores gas exchange in perfused lungs with alveolar fibrin formation

Alveolar fibrin generation has been suggested to possess strong surfactant-inhibitory potency. In perfused rabbit lungs, fibrin formation in the alveolar space was induced by sequential ultrasonic aerosolization of fibrinogen and thrombin, and the efficacy of rescue administration of surfactant and urokinase was investigated. Ventilation-perfusion (VA/Q) distribution was assessed by the multiple inert gas elimination technique. Aerosolization of fibrinogen (approximately 20 mg/kg body wt) increased shunt flow to approximately 7%. Sequential nebulization of fibrinogen and thrombin (1.3 U/kg body wt) caused alveolar fibrin deposition, documented immunohistologically, and provoked marked shunt flow, progressing to approximately 22% at the end of the experiments. The hemodynamics were virtually unchanged. Rescue aerosolization of natural bovine surfactant (15 mg/kg body wt) or urokinase-type plasminogen activator (4,500 U/kg body wt), undertaken after fibrin formation, improved gas exchange but progressive shunt flow still occurred (efficacy, surfactant > urokinase). In contrast, conebulization of surfactant and urokinase reversed shunt flow to approximately 7%, with an increased appearance of normal VA/Q matching. We conclude that alveolar fibrin formation is a potent surfactant-inhibitory mechanism in intact lungs, provoking severe VA/Q mismatch with a predominance of shunt flow, and that rescue aerosolization of surfactant plus urokinase may offer restoration of gas exchange under these conditions.     

Lobar contribution to VA/Q inequality during constant-flow ventilation

Previous studies have shown that normal arterial PCO2 can be maintained during apnea in anesthetized dogs by delivering a continuous stream of inspired ventilation through cannulas aimed down the main stem bronchi, although this constant-flow ventilation (CFV) was also associated with a significant increase in ventilation-perfusion (VA/Q) inequality, compared with conventional mechanical ventilation (IPPV). Conceivably, this VA/Q inequality might result from differences in VA/Q ratios among lobes caused by nonuniform distribution of ventilation, even though individual lobes are relatively homogeneous. Alternatively, the VA/Q inequality may occur at a lobar level if those factors causing the VA/Q mismatch also existed within lobes. We compared the efficiency of gas exchange simultaneously in whole lung and left lower lobe by use of the multiple inert gas elimination technique in nine anesthetized open-chest dogs. Measurements of whole lung and left lower lobe gas exchange allowed comparison of the degree of VA/Q inequality within vs. among lobes. During IPPV with positive end-expiratory pressure, arterial PO2 and PCO2 (183 +/- 41 and 34.3 +/- 3.1 Torr, respectively) were similar to lobar venous PO2 and PCO2 (172 +/- 64 and 35.7 +/- 4.1 Torr, respectively; inspired O2 fraction = 0.44 +/- 0.02). Switching to CFV (3 l.kg-1.min-1) decreased arterial PO2 (112 +/- 26 Torr, P less than 0.001) and lobar venous PO2 (120 +/- 27 Torr, P less than 0.01) but did not change the shunt measured with inert gases (P greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimation of ventilation-perfusion inequality by inert gas elimination without arterial sampling

Estimation of ventilation-perfusion (VA/Q) inequality by the multiple inert gas elimination technique requires knowledge of arterial, mixed venous, and mixed expired concentrations of six gases. Until now, arterial concentrations have been directly measured and mixed venous levels either measured or calculated by mass balance if cardiac output was known. Because potential applications of the method involve measurements over several days, we wished to determine whether inert gas levels in peripheral venous blood ever reached those in arterial blood, thus providing an essentially noninvasive approach to measuring VA/Q mismatch that could be frequently repeated. In 10 outpatients with chronic obstructive pulmonary disease, we compared radial artery (Pa) and peripheral vein (Pven) levels of the six gases over a 90-min period of infusion of the gases into a contralateral forearm vein. We found Pven reached 90% of Pa by approximately 50 min and 95% of Pa by 90 min. More importantly, the coefficient of variation at 50 min was approximately 10% and at 90 min 5%, demonstrating acceptable intersubject agreement by 90 min. Since cardiac output is not available without arterial access, we also examined the consequences of assuming values for this variable in calculating mixed venous levels. We conclude that VA/Q features of considerable clinical interest can be reliably identified by this essentially noninvasive approach under resting conditions stable over a period of 1.5 h.     

Contributions of ventilation and perfusion inhomogeneities to the VA/Q distribution.

The anatomic distributions of ventilation (VA) and perfusion (Q) in prone and supine dogs have been described in the literature. These data also provide frequency distributions, i.e., the distribution of lung units as a function of VA or Q. A comprehensive distribution that encompasses these two distributions is described, and the properties of the comprehensive distribution that determine the width of the VA/Q distribution are identified. Using data on the VA and Q distributions taken from various sources in the literature, we estimated the widths of the VA/Q distributions. The widths estimated from the independent data on the VA and Q distributions agree well with the widths obtained from gas exchange data. The analysis provides information about the relative contributions of the VA and Q distributions to the width of the VA/Q distribution. In the prone dog, the VA and Q distributions, as described by the available data, have different length scales, and we argue that these distributions are therefore not highly correlated. As a result, the variance of the VA/Q distributions is approximately the sum of the variances of the VA and Q distributions. Two-thirds of the variance in VA/Q is a result of nonuniform Q, and one-third is a result of nonuniform VA. In the supine dog, the variance of VA is larger than in the prone dog because of a vertical gradient and the variance of Q is larger, in part, because of a vertical gradient. Because the magnitudes of the vertical gradients of VA and Q are about equal, the vertical gradient of VA/Q is small, and these components of the VA and Q inhomogeneities contribute little to the width of the VA/Q distribution. The other components of Q inhomogeneity cause the additional variance of VA/Q in the supine dog.