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.     

Pulmonary hemodynamics and lung water content during splanchnic ischemic shock

Pulmonary hemodynamics and lung water content were evaluated in open-chest dogs during splanchnic arterial occlusion (SAO) shock. Mean pulmonary arterial pressure [Ppa = 13.0 +/- 0.6 (SE) mmHg] and pulmonary venous pressure (4.1 +/- 0.2 mmHg) were measured by direct cannulation and the capillary pressure (Ppc = 9.0 +/- 0.6 mmHg) estimated by the double-occlusion technique. SAO shock did not produce a significant change in Ppa or Ppc despite a 90% decrease in cardiac output. An 18-fold increase in pulmonary vascular resistance occurred, and most of this increase (70%) was on the venous side of the circulation. No differences in lung water content between shocked and sham-operated dogs were observed. The effect of SAO shock was further evaluated in the isolated canine left lower lobe (LLL) perfused at constant flow and outflow pressure. The addition of venous blood from shock dogs to the LLL perfusion circuit caused a transient (10-15 min) increase in LLL arterial pressure (51%) that could be reversed rapidly with papaverine. In this preparation, shock blood produced either a predominantly arterioconstriction or a predominantly venoconstriction. These results indicate that both arterial and venous vasoactive agents are released during SAO shock. The consistently observed venoconstriction in the intact shocked lung suggests that other factors, in addition to circulating vasoactive agents, contribute to the pulmonary hemodynamic response of the open-chest shocked dog.     

Characteristics of the pulmonary transport functions for heat and dye in pulmonary edema and orthostasis

The aim of this study was to investigate whether changes in the distribution of pulmonary blood flow and disturbances of the pulmonary microcirculation can be detected by use of inflow-outflow indicator-dilution measurements. In 18 anesthetized (N2O-piritramide) mongrel dogs 221 thermal-indocyanine green dye indicator dilution kinetics were recorded in the pulmonary artery and aorta after central venous indicator injection. The lagged normal density function was used as a model for the pulmonary transport functions for heat and dye. The parameters of the lagged normal density function were computed by a non-linear least squares procedure by iterative convolution. After baseline measurements, in nine dogs, pulmonary edema was induced by central venous application of oleic acid. In nine other dogs, measurements were performed before and after postural changes. Our data show that both the microvascular injury caused by oleic acid edema and the perfusion heterogeneity caused by orthostasis can be detected by the indicator dilution technique since the both relative dispersion and skewness of the transport functions for heat and dye were significantly increased after these interventions.     

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.     

Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect.

In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 +/- 0.6 ml x min(-1) x cm(-3) and was related to vertical height above the dependent lung (slope = -3%/cm, P < 0.0001). Lung density averaged 0.34 +/- 0.08 g/cm3 and was also related to vertical height (slope = -4.9%/cm, P < 0.0001). By contrast, when perfusion was normalized for regional lung density, the slope of the height-perfusion relationship was not significantly different from zero (P = 0.2). This suggests that in vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.     

Effects of embolus size on hemodynamics and gas exchange in canine embolic pulmonary hypertension

We examined the effects of different-sized glass-bead embolization on pulmonary hemodynamics and gas exchange in 12 intact anesthetized dogs. Pulmonary hemodynamics were evaluated by multipoint pulmonary arterial pressure (Ppa)/cardiac output (Q) plots before and 60 min after sufficient amounts of 100-microns (n = 6 dogs) or 1,000-microns (n = 6 dogs) glass beads to triple baseline Ppa were given and again 20 min after 5 mg/kg hydralazine in all the animals. Gas exchange was assessed using the multiple inert gas elimination technique in each of these experimental conditions. Embolization increased both the extrapolated pressure intercepts (by 6 mmHg) and the slopes (by 5 mmHg.l-1.min.m2) of the linear Ppa/Q plots, together with an 80% angiographic pulmonary vascular obstruction. These changes were not significantly different in the two subgroups of dogs. However, arterial PO2 was most decreased after the 100-microns beads, and arterial PCO2 was most increased after the 1,000-microns beads. Both bead sizes deteriorated the distribution of ventilation (VA)/perfusion (Q) ratios, with development of lung units with higher as well as with lower than normal VA/Q. Only 100-microns beads generated a shunt. Only 1,000-microns beads generated a high VA/Q mode and increased inert gas dead space. Hydralazine increased the shunt and decreased the slope of the Ppa/Q plots after 100-microns beads and had no effect after 1,000-microns beads. We conclude that in embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size up to 1,000 microns.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses.

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.     

Lung perfusion impairments in pulmonary embolic and airway obstruction with noncontrast MR imaging.

A noncontrast electrocardiography (ECG)-gated, fast-spin-echo magnetic resonance imaging was applied to noninvasively define perfusion impairments in pulmonary embolic and airway obstruction dog models. Two-phase ECG-gated lung images of the minimal lung signal intensity during systole and maximal signal intensity during diastole were acquired by using optimized R-wave triggering delay times in seven dogs anesthetized with pentobarbital sodium before, soon after, and 2 mo after embolization with enbucrilate and in another eight dogs before and after bronchial occlusion with balloon catheters, in combination with a gadolinium diethylenetriaminepentaacetic acid-enhanced dynamic study. An ECG-gated subtraction image between the two-phase lung images provided a uniform but gravity-dependent perfusion map in normal lungs. Furthermore, it defined all 13 variable-size perfusion deficits associated with pulmonary embolism and the dynamically decreased perfusion with time after bronchial occlusion in all the airway obstruction models. These results were consistent with contrast-enhanced pulmonary arterial perfusion phase images. This noncontrast imaging could be equivalent to a contrast-enhanced dynamic study in the definition of regionally impaired pulmonary arterial perfusion in pulmonary embolism and airway obstruction.     

Continuous cardiac output monitoring in humans by invasive and noninvasive peripheral blood pressure waveform analysis.

We present an evaluation of a novel technique for continuous (i.e., automatic) monitoring of relative cardiac output (CO) changes by long time interval analysis of a peripheral arterial blood pressure (ABP) waveform in humans. We specifically tested the mathematical analysis technique based on existing invasive and noninvasive hemodynamic data sets. With the former data set, we compared the application of the technique to peripheral ABP waveforms obtained via radial artery catheterization with simultaneous thermodilution CO measurements in 15 intensive care unit patients in which CO was changing because of disease progression and therapy. With the latter data set, we compared the application of the technique to noninvasive peripheral ABP waveforms obtained via a finger-cuff photoplethysmography system with simultaneous Doppler ultrasound CO measurements made by an expert in 10 healthy subjects during pharmacological and postural interventions. We report an overall CO root-mean-squared normalized error of 15.3% with respect to the invasive hemodynamic data set and 15.1% with respect to the noninvasive hemodynamic data set. Moreover, the CO errors from the invasive and noninvasive hemodynamic data sets were only mildly correlated with mean ABP (rho = 0.41, 0.37) and even less correlated with CO (rho = -0.14, -0.17), heart rate (rho = 0.04, 0.19), total peripheral resistance (rho = 0.38, 0.10), CO changes (rho = -0.26, -0.20), and absolute CO changes (rho = 0.03, 0.38). With further development and successful prospective testing, the technique may potentially be employed for continuous hemodynamic monitoring in the acute setting such as critical care and emergency care.     

Reduction of hypoxic pulmonary vasoconstriction during trichloroethylene anesthesia.

A double-lumen tube was inserted into the trachea of dogs anesthetized with intravenous pentobarbital (30-40 mg/kg). Blood flow/unit lung volume in each lung was measured with 133Xe. Both lungs were initially ventilated with oxygen and measurements of pulmonary blood flow, CO2 output, cardiac output, and blood gases were made. When nitrogen was administered to one lung blood flow was diverted to the opposite lung. The diversion of flow was reduced by the inhalation of 1% trichloroethylene but returned after withdrawal of the anesthetic. There were no significant changes in cardiac output. Changes in CO2 output and arterial Po2 were compatible with the xenon results. It is concluded that trichloroethylene may increase arterial hypoxemia by reducing vasoconstriction in hypoxic areas of lung.     

Response of the bronchial circulation to acute hypoxemia and hypercarbia in the dog

We have examined the effect of acute hypoxemia and hypercarbia on bronchial blood flow (Qbr) in 10 anesthetized, ventilated, open-chest dogs using a modification of the radioactive microsphere technique. After surgery, dogs were divided into two groups of five. Group 1 was ventilated for 30 min with each of the following gas mixtures: 1) room air; 2) 15% O2-85% N2; 3) 10% O2-90% N2, and group 2 with 1) room air; 2) 5% CO2-30% O2-65% N2; 3) 10% CO2-30% O2-60% N2. Measurements of pulmonary arterial, left atrial and aortic pressures, cardiac output, and blood gases were made before injection of 46Sc-, 153Gd-, and 103Ru-labeled microspheres into the left atrium as a marker of Qbr. After the final measurements, dogs were killed and the lungs removed and the parenchyma stripped off the large and small airways of the left lung. Knowing the radioactivity in the trachea, bronchi, parenchyma, and in the blood from the reference-flow sample and also the aortic and left atrial pressures, total and regional Qbr, and bronchovascular resistance (BVR) were calculated. Results showed that acute hypoxemia (10% O2) caused a significant (P less than 0.05) decrease in Qbr and increase in BVR and acute hypercarbia (10% CO2) caused a significant (P less than 0.05) increase in Qbr and decrease in BVR.     

Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep

The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338-342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37-42 Torr, arterial CO2 tension (PaCO2) = 25-30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19-22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7-10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep.     

Measurement of bronchial blood flow with radioactive microspheres in awake sheep

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs.

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.     

Effect of pulmonary blood flow on leukocyte uptake and release by dog lung

The effect of pulmonary blood flow on leukocyte uptake and release by the lung was examined in 10 anesthetized spontaneously breathing dogs. Pulmonary arterial and pulmonary venous blood was sampled with catheters placed into the right ventricle and aorta, respectively. Pulmonary blood flow was lowered by inflating a balloon catheter located in the inferior vena cava. In five experiments simultaneous blood samples were drawn from the right ventricle and aorta at 10-s intervals during a control period, a 2- to 3-min period of low flow, and a recovery period. In five additional experiments, less frequent samples were taken over periods of 15-60 min. Total leukocyte concentrations and differential counts were determined for each blood sample. The study shows that large numbers of leukocytes become sequestered within the lung when pulmonary blood flow is low and that an equivalent number of cells are released from the lung after deflation of the balloon catheter. Both the polymorphonuclear leukocytes and the lymphocytes were taken up by the lung when pulmonary blood flow was reduced. We conclude that pulmonary blood flow has a marked effect on the uptake and release of leukocytes by the dog lung.     

Role of tracheal and bronchial circulation in respiratory heat exchange

Due to their anatomic configuration, the vessels supplying the central airways may be ideally suited for regulation of respiratory heat loss. We have measured blood flow to the trachea, bronchi, and lung parenchyma in 10 anesthetized supine open-chest dogs. They were hyperventilated (frequency, 40; tidal volume 30-35 ml/kg) for 30 min or 1) warm humidified air, 2) cold (-20 degrees C dry air, and 3) warm humidified air. End-tidal CO2 was kept constant by adding CO2 to the inspired ventilator line. Five minutes before the end of each period of hyperventilation, measurements of vascular pressures (pulmonary arterial, left atrial, and systemic), cardiac output (CO), arterial blood gases, and inspired, expired, and tracheal gas temperatures were made. Then, using a modification of the reference flow technique, 113Sn-, 153Gd-, and 103Ru-labeled microspheres were injected into the left atrium to make separate measurements of airway blood flow at each intervention. After the last measurements had been made, the dogs were killed and the lungs, including the trachea, were excised. Blood flow to the trachea, bronchi, and lung parenchyma was calculated. Results showed that there was no change in parenchymal blood flow, but there was an increase in tracheal and bronchial blood flow in all dogs (P less than 0.01) from 4.48 +/- 0.69 ml/min (0.22 +/- 0.01% CO) during warm air hyperventilation to 7.06 +/- 0.97 ml/min (0.37 +/- 0.05% CO) during cold air hyperventilation.     

Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs

Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.     

Lung mechanics in hypervolemic pulmonary edema.

Extravascular thermal volume of the lung (ETVL) is a double indicator dilution technique of use in measuring pulmonary edema. ETVL and lung mechanics measurements were followed to find a less invasive monitor of pulmonary edema than the double indicator dilution technique. Pulmonary edema was induced by overloading the dogs' circulation with dextran. Phases of overload were defined on the basis of a previous electron microscopic study (Noble et al., Can. Anesthetists Soc. J. 21:275, 1974) of lung biopsies relating anatomic changes to physiologic measurements of ETVL and central blood volume (CBV). Congestion occurred when CBV was elevated and ETVL was not, interstitial edema when ETVL was elevated but smaller than 60% above control and alveolar edema when ETVL greater than 85% above control. Once the dogs were in alveolar edema, they were mechanically ventilated with 4, 8, 12, and 16 cmH2O end-tidal pressure (CPPV). Mean functional residual capacity (FRC) for all 15 dogs did not change up to the time CPPV was applied. Pulmonary resistance did not rise until alveolar edema was present. Once in pulmonary edema, lung compliance always fell as lung water increased. In individual dogs, the compliance fall was directly proportional to the rising lung water. However, the variations in slope and beginning point among dogs made it difficult to predict the amount of lung water from dynamic compliance values. PaO2 fell markedly in alveolar edema as a result of a widened A-a gradient. CPPV did not decrease lung water but did increase FRC and PaO2.     

Meclofenamate enhances blood oxygenation in acute oleic acid lung injury

To assess the role of vasoactive prostanoids in acute lung injury, we studied 16 dogs after intravenous injection of oleic acid (OA; 0.08 ml/kg). Animals were ventilated with 100% O2 and zero end-expiratory pressure. Base-line hemodynamic and blood gas observations were obtained 90-120 min following OA. Observations were repeated 30 min after infusion of meclofenamate (2 mg/kg; n = 10), or after saline (n = 6). Resistance to pulmonary blood flow was assessed using the difference between pulmonary arterial diastolic and left atrial pressures (PDG). Ventilation-perfusion (VA/Q) distributions were derived with the multiple inert gas technique. Prior to infusion, there were no significant differences between the two groups. PDG was elevated mildly above normal levels, and shunt flow was the principal gas exchange disturbance. Saline induced no significant changes in hemodynamics or gas exchange. Meclofenamate enhanced PDG to a small, significant degree and effected a 32% reduction in shunt flow (P less than 0.01). Perfusion was redistributed to normal VA/Q units with little change in low VA/Q perfusion or in overall flow. Arterial PO2 rose from 75 +/- 36 to 184 +/- 143 Torr (P less than 0.05). At autopsy, there were no significant differences in wet to dry lung weights. Prostaglandin inhibition redistributes perfusion from shunt to normal VA/Q units, thereby improving arterial PO2, without altering lung water acutely.     

Pulmonary pressure-flow relationships in the fetal lamb during in utero ventilation

Pressure-flow relationships in the ventilated lung have not been previously determined in undelivered fetal sheep. Therefore we studied 11 late-gestation chronically prepared fetal sheep during positive-pressure ventilation with different gas mixtures to determine the roles of mechanical distension and blood gas tensions on pressure-flow relationships in the lung. Ventilation with 3% O2-7% CO2 produced a substantial fall in pulmonary vascular resistance even though arterial blood gases were not changed. Increases in pulmonary arterial PO2 during ventilation were associated with falls in pulmonary vascular resistance beyond that measured during mechanical distension. Decreases in pulmonary arterial PCO2 and associated increases in pH were also associated with falls in pulmonary vascular resistance. Pulmonary blood flow ceased at a pulmonary arterial pressure that exceeded left atrial pressure, indicating that left atrial pressure does not represent the true downstream component of driving pressure through the pulmonary vascular bed. The slope of the driving pressure-flow relationship in the normal mature fetal lamb was therefore different from the ratio of pulmonary arterial pressure to pulmonary arterial flow. We conclude that mechanical ventilation, increased PO2 and decreased PCO2, and/or increased pH has an important influence on the fall in pulmonary vascular resistance elicited by positive pressure in utero ventilation of the fetal lamb and that the downstream driving pressure for pulmonary blood flow exceeds left atrial pressure.