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.     

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)     

Alveolar pressure inhomogeneity and gas exchange during constant-flow ventilation in dogs

Analysis of momentum transfer between inflow jets and resident gas during constant-flow ventilation (CFV) predicts inhomogeneity of alveolar pressures (PA) and volume, which might account for specific ventilation-variance in the lung. Using alveolar needles to measure pressures (PA) during CFV in eight anesthetized dogs with wide thoracotomy, we observed random dispersion of PA among lobes of up to 12.5 cmH2O. Within each lobe, the PA dispersion was up to 10 cmH2O at CFV of 90 l/min; when flow decreased, PA at all sites decreased, as did the intralobar dispersion. These pressure differences were not observed during conventional mechanical ventilation (CMV). During CFV with room air, dogs were hypoxemic [arterial PO2 (Pao2) 54 +/- 15 Torr] and the venous admixture (Qva/QT) was 50 +/- 15%. When inspiratory O2 fraction was increased to 0.4, Pao2 increased to 172 +/- 35 Torr and Qva/QT dropped to 13.5 +/- 8.4%, confirming considerable ventilation-perfusion (VA/Q) variance not observed during CMV. We conclude that momentum transfer between the inflow stream and resident gas caused inhomogeneities of alveolar pressures, volumes, and ventilation responsible for VA/Q variance and hypoxemia during CFV. Conceivably, the abnormal ventilation distribution is minimized by collateral ventilation and forces of interdependence between regions of high and low alveolar pressures. Momentum transfer also predicted the mucosal damage observed on histological evaluation of the bronchial walls near the site of inflow jet impact.     

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.     

Effects of inspired CO2, hyperventilation, and time on VA/Q inequality in the dog.

In a recent study by Tsukimoto et al. (J. Appl. Physiol. 68: 2488-2493, 1990), CO2 inhalation appeared to reduce the size of the high ventilation-perfusion ratio (VA/Q) mode commonly observed in anesthetized mechanically air-ventilated dogs. In that study, large tidal volumes (VT) were used during CO2 inhalation to preserve normocapnia. To separate the influences of CO2 and high VT on the VA/Q distribution in the present study, we examined the effect of inspired CO2 on the high VA/Q mode using eight mechanically ventilated dogs (4 given CO2, 4 controls). The VA/Q distribution was measured first with normal VT and then with increased VT. In the CO2 group at high VT, data were collected before, during, and after CO2 inhalation. With normal VT, there was no difference in the size of the high VA/Q mode between groups [10.5 +/- 3.5% (SE) of ventilation in the CO2 group, 11.8 +/- 5.2% in the control group]. Unexpectedly, the size of the high VA/Q mode decreased similarly in both groups over time, independently of the inspired PCO2, at a rate similar to the fall in cardiac output over time. The reduction in the high VA/Q mode together with a simultaneous increase in alveolar dead space (estimated by the difference between inert gas dead space and Fowler dead space) suggests that poorly perfused high VA/Q areas became unperfused over time. A possible mechanism is that elevated alveolar pressure and decreased cardiac output eliminate blood flow from corner vessels in nondependent high VA/Q regions.     

Effect of common dead space on VA/Q distribution in the dog

Several previous studies have shown worsening ventilation-perfusion (VA/Q) relationships in humans during heavy exercise at sea level. However, the mechanism of this deterioration remains unclear because of the correlation with ventilatory and circulatory variables. Our hypothesis was that the decrease in the series dead space-to-tidal volume ratio during exercise might be partly responsible because mixing in the common dead space can reduce apparent inequality. We tested this notion in 10 resting anesthetized normocapnic dogs passively hyperventilated by increase tidal volume and a) inspired CO2 or b) external dead space. We predicted less apparent VA/Q inequality in condition b because of mixing in the added dead space. After base-line measurements, conditions a and b were randomly assigned, and after a second set of base-line measurements they were repeated in the reverse order in each dog. VA/Q inequality was measured by the multiple inert gas elimination technique. Comparison of conditions a and b demonstrated that additional external dead space improved (P less than 0.001) the blood flow distributions as hypothesized [log standard deviation of perfusion = 0.49 +/- 0.02 (SE) in condition b and 0.61 +/- 0.03 in condition a with respect to 0.52 +/- 0.03 at base line]. This study suggests that the increased tidal volume during exercise could uncover VA/Q inequality not evident at rest because of the higher ratio of common dead space to tidal volume at rest.     

Pressure, flow, and density relationships in airway models during constant-flow ventilation

Adequate CO2 elimination and normal arterial PCO2 levels can be maintained in dogs during apnea by delivering a continuous flow of inspired gas at high flow rate (1-3 l.min-1.kg-1) through tubes placed in the main-stem bronchi. However, during constant-flow ventilation (CFV) the mean alveolar pressure is increased, causing increased lung volume despite low pressures in the trachea. We hypothesized that the increased dynamic alveolar pressures during CFV were due to momentum transfer from the high-velocity jet stream to resident gas in the lung. To test this, we simulated CFV in straight tubes and in a branched airway model to determine whether changes in gas flow rate (V), gas density (rho), and tube diameter (D) altered the pressure difference (delta P) between alveoli and airway opening in a manner consistent with that predicted by conservation of momentum. Momentum analysis predicts that delta P should vary with V2, whereas measurements yielded a dependence of V1.69 in branched tubes and V1.9 in straight tubes. Substitution of heliox (80% He-20% O2) for air significantly reduced lung hyperinflation during CFV. As predicted by momentum transfer, delta P varied with rho 1.0. Momentum analysis also predicts that delta P should vary with D-2.0, whereas measurements indicated a dependence on D-2.02. The influence of V and rho on depth of penetration of the jet down the airway was explored in a straight tube model by varying the flow rate and gas used. The influence of geometry on penetration was measured by changing the ratio of jet-to-airway tube diameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination of constant-flow and continuous positive-pressure ventilation in canine pulmonary edema

Constant-flow ventilation (CFV) maintains alveolar ventilation without tidal excursion in dogs with normal lungs, but this ventilatory mode requires high CFV and bronchoscopic guidance for effective subcarinal placement of two inflow catheters. We designed a circuit that combines CFV with continuous positive-pressure ventilation (CPPV; CFV-CPPV), which negates the need for bronchoscopic positioning of CFV cannula, and tested this system in seven dogs having oleic acid-induced pulmonary edema. Addition of positive end-expiratory pressure (PEEP, 10 cmH2O) reduced venous admixture from 44 +/- 17 to 10.4 +/- 5.4% and kept arterial CO2 tension (PaCO2) normal. With the innovative CFV-CPPV circuit at the same PEEP and respiratory rate (RR), we were able to reduce tidal volume (VT) from 437 +/- 28 to 184 +/- 18 ml (P less than 0.001) and elastic end-inspiratory pressures (PEI) from 25.6 +/- 4.6 to 17.7 +/- 2.8 cmH2O (P less than 0.001) without adverse effects on cardiac output or pulmonary exchange of O2 or CO2; indeed, PaCO2 remained at 35 +/- 4 Torr even though CFV was delivered above the carina and at lower (1.6 l.kg-1.min-1) flows than usually required to maintain eucapnia during CFV alone. At the same PEEP and RR, reduction of VT in the CPPV mode without CFV resulted in CO2 retention (PaCO2 59 +/- 8 Torr). We conclude that CFV-CPPV allows CFV to effectively mix alveolar and dead spaces by a small bulk flow bypassing the zone of increased resistance to gas mixing, thereby allowing reduction of the CFV rate, VT, and PEI for adequate gas exchange.     

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.     

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.     

Correlation between ventilation and perfusion determines VA/Q heterogeneity in endotoxemia.

Endotoxin increases ventilation-to-perfusion ratio (VA/Q) heterogeneity in the lung, but the precise changes in alveolar ventilation (VA) and perfusion that lead to VA/Q heterogeneity are unknown. The purpose of this study was to determine how endotoxin affects the distributions of ventilation and perfusion and the impact of these changes on VA/Q heterogeneity. Seven anesthetized, mechanically ventilated juvenile pigs were given E. coli endotoxin intravenously, and regional ventilation and perfusion were measured simultaneously by using aerosolized and injected fluorescent microspheres. Endotoxemia significantly decreased the correlation between regional ventilation and perfusion, increased perfusion heterogeneity, and redistributed perfusion between lung regions. In contrast, ventilation heterogeneity did not change, and redistribution of ventilation was modest. The decrease in correlation between regional ventilation and perfusion was responsible for significantly more VA/Q heterogeneity than were changes in ventilation or perfusion heterogeneity. We conclude that VA/Q heterogeneity increases during endotoxemia primarily as a result of the decrease in correlation between regional ventilation and perfusion, which is in turn determined primarily by changes in perfusion.     

Gas exchange and intrapulmonary distribution of ventilation during continuous-flow ventilation

In 12 anesthetized paralyzed dogs, pulmonary gas exchange and intrapulmonary inspired gas distribution were compared between continuous-flow ventilation (CFV) and conventional mechanical ventilation (CMV). Nine dogs were studied while they were lying supine, and three dogs were studied while they were lying prone. A single-lumen catheter for tracheal insufflation and a double-lumen catheter for bilateral endobronchial insufflation [inspired O2 fraction = 0.4; inspired minute ventilation = 1.7 +/- 0.3 (SD) 1.kg-1.min-1] were evaluated. Intrapulmonary gas distribution was assessed from regional 133Xe clearances. In dogs lying supine, CO2 elimination was more efficient with endobronchial insufflation than with tracheal insufflation, but the alveolar-arterial O2 partial pressure difference was larger during CFV than during CMV, regardless of the type of insufflation. By contrast, endobronchial insufflation maintained both arterial PCO2 and alveolar-arterial O2 partial pressure difference at significantly lower levels in dogs lying prone than in dogs lying supine. In dogs lying supine, the dependent lung was preferentially ventilated during CMV but not during CFV. In dogs lying prone, gas distribution was uniform with both modes of ventilation. The alveolar-arterial O2 partial pressure difference during CFV in dogs lying supine was negatively correlated with the reduced ventilation of the dependent lung, which suggests that increased ventilation-perfusion mismatching was responsible for the increase in alveolar-arterial O2 partial pressure difference. The more efficient oxygenation during CFV in dogs lying prone suggests a more efficient matching of ventilation to perfusion, presumably because the distribution of blood flow is also nearly uniform.     

A visual aid for teaching ventilation-perfusion relationships

To help students understand the concept of the ventilation-perfusion ratio (VA/Q) and the effects that VA/Q mismatching has on pulmonary gas exchange, a "sliding rectangles" visual aid was developed to teach VA/Q relationships. Adjacent rectangles representing "ventilation" and "perfusion" are slid past one another so that portions of the ventilation and perfusion rectangles are not touching, illustrating the concepts of dead-space ventilation (VD) and shunt flow (QS). The portion of the ventilation bar representing VD is further subdivided into anatomical and alveolar VD and used to show the effects of alveolar dead space on the PO2 (PAO2) and PCO2 of alveolar air (PACO2); movement away from the "ideal" point). Similarly, the portion of the perfusion bar representing QS is used to define anatomical and physiological shunts and the effect of shunts on the PO2 (PaO2) and PCO2 of arterial blood (PaCO2). The genesis of the PAO2-PaO2 (A-a) PO2 difference as well as the effects of VA/Q mismatching and diffusion abnormalities can all be discussed with this visual aid. This approach has greatly assisted some students in mastering this traditionally difficult area of respiratory physiology.     

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.     

Low VA/Q areas: arterial-alveolar N2 difference and multiple inert gas elimination technique

In 16 critically ill patients the arterial-alveolar N2 difference and data from the multiple inert gas elimination technique (MIGET) were compared in the evaluation of the contribution of low alveolar ventilation-perfusion ratio (VA/Q) lung regions (0.005 less than VA/Q less than 0.1) to venous admixture (Qva/QT). The arterial-alveolar N2 difference was determined using a manometric technique for the measurement of the arterial N2 partial pressure (PN2). We adopted a two-compartment model of the lung, one compartment having a VA/Q of approximately 1, the other being open, gas filled, unventilated (VA/Q = 0), and in equilibrium with the mixed venous blood. This theoretical single compartment represents all lung regions responsible for the arterial-alveolar N2 difference. The fractional blood flow to this compartment was calculated using an appropriate mixing equation (Q0/QT). There was a weak but significant relationship between Q0/QT and the perfusion fraction to lung regions with low VA/Q (0.005 less than VA/Q less than 0.1) (r = 0.542, P less than 0.05) and a close relationship between Q0/QT and the perfusion fraction to lung regions with VA/Q ratios less than 0.9 (r = 0.862, P less than 0.001) as obtained from MIGET. The difference Qva/QT-Q0/QT yielded a close estimation of the MIGET right-to-left shunt (Qs/QT) (r = 0.962, P less than 0.001). We conclude that the assessment of the arterial-alveolar N2 difference and Q0/QT does not yield a quantitative estimation of the contribution of pathologically low VA/Q areas to QVa/QT because these parameters reflect an unknown combination of pathological and normal (0.1 less than VA/Q less than 0.9) gas exchange units.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary gas exchange in humans during normobaric hypoxic exercise

Previous studies (J. Appl. Physiol. 58: 978-988 and 989-995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of regional V/Q ratios in humans by use of PET. I. Theory

With positron emission tomography, quantitative measurements of regional alveolar and mixed venous concentrations of positron-emitting radioisotopes can be made within a transaxial section through the thorax. This allows the calculation of regional ventilation-to-perfusion (V/Q) ratios by use of established tracer dilution theory and the constant intravenous infusion of 13N. This paper considers the effect of the inspiration of dead-space gas on regional V/Q and investigates the relationship between the measured V/Q, physiological V/Q, and V/Q defined conventionally in terms of bulk gas flow (VA/Q). Ventilation has been described in terms of net gas transport, and the term effective ventilation has been introduced. A simple two-compartment model has been constructed to allow for the reinspiration of regional (or personal) and common dead-space gas. By use of this model, with parameters representative of normal lung the effective V/Q ratio for 13N [(VA/Q)eff(13N)] is shown to overestimate VA/Q by 18% when VA/Q = 0.1 but underestimate VA/Q by 68% when VA/Q = 10. For physiological gases, the model predicts that the behavior of O2 should be similar to that of 13N, so that, in terms of gas transport, V/Q ratios obtained using the infusion of 13N closely follow those for O2. Values of the effective V/Q ratio for CO2 [(VA/Q)eff(CO2)] lie approximately halfway between (VA/Q)eff(13N) and VA/Q. These results indicate that dead-space ventilation is far less a confounding issue when V/Q is considered in terms of net gas transport (VAeff), rather than bulk flow (VA).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of high-frequency ventilation in presence of extensive ventilation-perfusion mismatch

Ten anesthetized normal dogs were each given two methacholine inhalational challenges to produce large amounts of low ventilation-perfusion (VA/Q) regions but little shunt. After one challenge, high-frequency ventilation (HFV) was applied, whereas after the other conventional mechanical ventilation (MV) was used, the order being randomized. Levels of both ventilatory modes were selected prior to challenge so as to result in similar and normal mean airway pressures and arterial PCO2 levels during control conditions. Gas exchange was assessed by both respiratory and multiple inert-gas transfer. Comparing the effect of HFV and MV, no statistically significant differences were found for lung resistance, pulmonary hemodynamic indices, arterial and mixed venous PO2, expired-arterial PO2 differences, or inert-gas data expressed as retention-excretion differences. The only variables that were different were mean airway pressure (2 cm higher during HFV, P less than 0.04) and arterial PCO2 (10 Torr higher during HFV, P less than 0.002). These results suggest that in this canine model of lung disease characterized by large amounts of low VA/Q regions, HFV is no more effective in delivering fresh gas to such regions than is MV.     

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.     

Reproducibility of the multiple inert gas elimination technique

Although measurement errors in the multiple inert gas elimination technique have a coefficient of variation of approximately 3%, small biological fluctuations in ventilation, blood flow, or other variables must contribute additional variance to this method of assessing ventilation-perfusion (VA/Q) mismatch. To determine overall variance of computed indices of VA/Q mismatch, an analysis of variance was carried out using a total of 400 duplicate pairs of inert gas samples obtained from canine (N = 118) and human (N = 282) studies in the past 2 years. In both sets VA/Q mismatch ranged from minimal (2nd moment of ventilation and blood flow distributions, log SDV and log SDQ, respectively approximately equal to 0.3 each) to severe (log SDV and log SDQ approximately equal to 2.0). Differences between duplicate log SD values were computed and found to be a constant fraction of the mean log SD of each duplicate pair, averaging 13% for both canine and human ventilation and blood flow data. The resultant coefficient of variation for a single measurement of log SD about its mean averaged 8.6% for all data combined. This analysis demonstrates excellent reproducibility of these dispersion indices over a wide range of conditions, and if the mean of duplicate values is used, thus reducing variability by square root 2 to 6.1%, log SD can be estimated with an approximately 95% confidence limit of +/- 12%.