Ventilation-perfusion inhomogeneity increases gas uptake in anesthesia: computer modeling of gas exchange.

Ventilation-perfusion (VA/Q) inhomogeneity was modeled to measure its effect on overall gas exchange during maintenance-phase N(2)O anesthesia with an inspired O(2) concentration of 30%. A multialveolar compartment computer model was used based on physiological log normal distributions of VA/Q inhomogeneity. Increasing the log standard deviation of the distribution of perfusion from 0 to 1.75 paradoxically increased O(2) uptake (VO(2)) where a low mixed venous partial pressure of N(2)O [high N(2)O uptake (VN(2)O)] was specified. With rising mixed venous partial pressure of N(2)O, a threshold was observed where VO(2) began to fall, whereas VN(2)O began to rise with increasing VA/Q inhomogeneity. This phenomenon is a magnification of the concentrating effects that VO(2) and VN(2)O have on each other in low VA/Q compartments. During "steady-state" N(2)O anesthesia, VN(2)O is predicted to paradoxically increase in the presence of worsening VA/Q inhomogeneity.     

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.     

Effect of local pulmonary blood flow control on gas exchange: theory

The effect of local pulmonary blood flow control by local alveolar O2 tension on steady-state pulmonary gas exchange is analyzed with techniques derived from control theory. In a single homogeneous lung unit with normal inspired and mixed venous blood gas composition, the homeostatic effect on local ventilation-perfusion ratios (VA/Q) regulation occurs over a restricted range of VA/Q. The homeostatic effect is maximal at a moderately low VA/Q (about 0.4) due to the slope of the O2 dissociation curve. In a multicompartment lung with a lognormal distribution of VA/Q, regulation of arterial O2 tension varies with the extent of inhomogeneity. At mild degrees of inhomogeneity where local pulmonary blood flow (Q) control acts predominantly on the lower VA/Q of the Q distribution, the regulatory effect is best. At severe degrees of inhomogeneity where local Q control acts mainly on the higher VA/Q of the Q distribution, the regulatory effect is worse, and positive-feedback behavior may occur. Local Q control has the potential of reducing the deleterious effects of lung disease on pulmonary gas exchange particularly when it operates in association with other regulatory mechanisms.     

Ventilation-perfusion lines and gas exchange in liquid breathing: theory

Alveolar exchange of a gas is governed by the ventilation-perfusion ratio (VA/Q) and the Ostwald partition coefficient for that species. We altered the Ostwald coefficients for O2 and CO2 by considering an animal breathing water or a fluorocarbon (FC-80) and studied the effects on gas exchange. Among our conclusions are the following. 1) When the ratio of the CO2 to O2 solubility in the inspirate exceeds the ratio of the O2 to the CO2 slope of the blood dissociation curve, as in water breathing, the VA/Q line becomes concave upward, and elements having a low VA/Q differ from each other more in terms of CO2 than of O2. 2) As the ratio of the CO2 to O2 solubility in the inspired medium increases, CO2 elimination becomes more dependent on perfusion. 3) At times, the same R will prevail in areas having different VA/Q values. 4) The alveolar-to-arterial O2 and CO2 differences resulting from a given VA/Q distribution do not depend on the O2 and CO2 solubility coefficients of the inspired medium, but on the inspired and mixed venous concentrations necessary to maintain adequate arterial gas levels in the presence of different inspired media.     

Influence of Bohr-Haldane effect on steady-state gas exchange

The influence of the Bohr-Haldane effect (BH) on steady-state gas exchange has previously been described by its effect of gas transfer from the blood when arterial and venous blood gas tensions were held constant. This report quantifies by computer analysis the effects of BH when either or both arterial and venous blood gas tensions are subject to change. When mixed venous blood gas composition is held constant, elimination of BH from a single lung unit typically reduces CO2 output by 6.5% and O2 uptake by 0.5%. Similar effects occur in a two-compartment lung model whether alveolar ventilation-perfusion (VA/Q) mismatch occurs in a parallel or series ventilatory arrangement. When arterial blood gas composition is held constant, elimination of BH increases systemic venous CO2 partial pressure, but O2 partial pressure is hardly affected in the absence of metabolic acidosis. When both mixed venous and arterial blood gas tensions vary and gas exchange is stressed by VA/Q inequality, altitude, anemia, or exercise, elimination of BH predominantly affects mixed venous rather than arterial blood gas tensions. it is concluded that BH may act primarily to reduce tissue acidosis.     

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)     

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)     

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.     

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)     

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 is not impaired 24 h after extravehicular activity.

Extravehicular activity (EVA) during spaceflight involves a significant decompression stress. Previous studies have shown an increase in the inhomogeneity of ventilation-perfusion ratio (VA/Q) after some underwater dives, presumably through the embolic effects of venous gas microemboli in the lung. Ground-based chamber studies simulating EVA have shown that venous gas microemboli occur in a large percentage of the subjects undergoing decompression, despite the use of prebreathe protocols to reduce dissolved N(2) in the tissues. We studied eight crewmembers (7 male, 1 female) of the International Space Station who performed 15 EVAs (initial cabin pressure 748 mmHg, final suit pressure either approximately 295 or approximately 220 mmHg depending on the suit used) and who followed the denitrogenation procedures approved for EVA from the International Space Station. The intrabreath VA/Q slope was calculated from the alveolar Po(2) and Pco(2) in a prolonged exhalation maneuver on the day after EVA and compared with measurements made in microgravity on days well separated from the EVA. There were no significant changes in intrabreath VA/Q slope as a result of EVA, although there was a slight increase in metabolic rate and ventilation (approximately 9%) on the day after EVA. Vital capacity and other measures of pulmonary function were largely unaltered by EVA. Because measurements could only be performed on the day after EVA because of logistical constraints, we were unable to determine an acute effect of EVA on VA/Q inequality. The results suggest that current denitrogenation protocols do not result in any major lasting alteration to gas exchange in the lung.     

Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.     

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)     

Effects of hyperoxia on vasoconstriction and VA/Q matching in the neonatal lung

Exposure of adult animals to 48-72 h of 100% O2 breathing is associated with a blunting of hypoxic pulmonary vasoconstriction (HPV) (Newman et al. J. Appl. Physiol. 54: 1379-1386, 1983). It is unknown whether HPV is also diminished in neonates after hyperoxic exposure and if so to what extent such suppression might interfere with pulmonary gas exchange during hypoxic gas breathing. We tested the possibility that hyperoxia would suppress HPV and interfere with ventilation-perfusion (VA/Q) matching and therefore gas exchange in neonatal piglets. Twelve 2- to 4-wk-old piglets were exposed for an average of 68 h to greater than 90% inspired O2. A control group of eight piglets was exposed to room air for a similar period of time. Immediately after exposure the animals were anesthetized and instrumented. Pulmonary hemodynamics and respiratory and inert gas exchange were assessed while the animals inspired an O2 fraction of 1.0, 0.21, and 0.12. After 20 min of hypoxic gas breathing, pulmonary arterial pressure rose to a lesser degree in the hyperoxia (H)-exposed animals than in the control (C) animals (P less than 0.02). The increase in pulmonary vascular resistance was similarly blunted. Venous admixture of the insoluble inert gas, sulfur hexafluoride, an index of extremely low VA/Q areas, was increased during hypoxic gas breathing compared with room air breathing in the H-preexposed animals (P less than 0.02). Standard deviation of pulmonary blood flow was increased (P less than 0.02), indicating an increase in mismatching of VA/Q during hypoxic breathing in the H-preexposed animals compared with the C animals.(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)     

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.     

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.     

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.     

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.     

Validation of measurements of ventilation-to-perfusion ratio inequality in the lung from expired gas.

The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (Va/Q) inequality in the lung. To further validate this estimate, we examined three measures of Va/Q inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of Va/Q inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreath Va/Q (iV/Q), the best index was the slope of iV/Q vs. volume over phase III (iV/Q slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for iV/Q slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement of Va/Q inhomogeneity can be derived from the intrabreath respiratory exchange ratio.