Effect of ventilation with soluble and diffusible gases on the size of air emboli

Pulmonary hypertension resulting from venous air embolism is known to increase after ventilation with highly soluble and diffusible gases. Exacerbation of the hypertension could be due to further blockage of the circulation if the bubbles enlarge as a result of ingress of gas by diffusion. This mechanism has been frequently cited but lacks direct proof. To determine directly whether intravascular air bubbles actually enlarge when highly soluble and diffusible gases are inspired, we used microscopy to measure the size of gas emboli in vivo. When air bubbles were injected into the right atrium, the bubbles that appeared in pulmonary arterioles were larger during ventilation with helium or nitrous oxide than with air. Air bubbles injected into the pulmonary artery enlarged when the inspired gas was changed to helium or nitrous oxide. The direction, magnitude, and timing of changes in bubble size were consistent with a net diffusion of gas into the bubbles. These data support the idea that venous air emboli enlarge during ventilation with soluble and diffusible gases and thereby cause further vascular obstruction.     

Evidence for active control of perfusion within lung microvessels

Vasoconstrictors cause contraction of pulmonary microvascular endothelial cells in culture. We wondered if this meant that contraction of these cells in situ caused active control of microvascular perfusion. If true, it would mean that pulmonary microvessels were not simply passive tubes and that control of pulmonary microvascular perfusion was not mainly due to the contraction and dilation of arterioles. To test this idea, we vasoconstricted isolated perfused rat lungs with angiotensin II, bradykinin, serotonin, or U46619 (a thromboxane analog) at concentrations that produced equal flows. We also perfused matched-flow controls. We then infused a bolus of 3 μm diameter particles into each lung and measured the rate of appearance of the particles in the venous effluent. We also measured microscopic trapping patterns of particles retained within each lung. Thirty seconds after particle infusion, venous particle concentrations were significantly lower (P ≤ 0.05) for lungs perfused with angiotensin II or bradykinin than for those perfused with U46619, but not significantly different from serotonin perfused lungs or matched flow controls. Microscopic clustering of particles retained within the lungs was significantly greater (P ≤ 0.05) for lungs perfused with angiotensin II, bradykinin, or serotonin, than for lungs perfused with U46619 or for matched flow controls. Our results suggest that these agents did not produce vasoconstriction by a common mechanism and support the idea that pulmonary microvessels possess a level of active control and are not simply passive exchange vessels.     

Exercise-induced intrapulmonary shunting of venous gas emboli does not occur after open-sea diving.

Paradoxical arterializations of venous gas emboli can lead to neurological damage after diving with compressed air. Recently, significant exercise-induced intrapulmonary anatomical shunts have been reported in healthy humans that result in widening of alveolar-to-arterial oxygen gradient. The aim of this study was to examine whether intrapulmonary shunts can be found following strenuous exercise after diving and, if so, whether exercise should be avoided during that period. Eleven healthy, military male divers performed an open-sea dive to 30 m breathing air, remaining at pressure for 30 min. During the bottom phase of the dive, subjects performed mild exercise at approximately 30% of their maximal oxygen uptake. The ascent rate was 9 m/min. Each diver performed graded upright cycle ergometry up to 80% of the maximal oxygen uptake 40 min after the dive. Monitoring of venous gas emboli was performed in both the right and left heart with an ultrasonic scanner every 20 min for 60 min after reaching the surface pressure during supine rest and following two coughs. The diving profile used in this study produced significant amounts of venous bubbles. No evidence of intrapulmonary shunting was found in any subject during either supine resting posture or any exercise grade. Also, short strenuous exercise after the dive did not result in delayed-onset decompression sickness in any subject, but studies with a greater number of participants are needed to confirm whether divers should be allowed to exercise after diving.     

Influence of pulmonary embolism on absorption of inhaled iodide-125

To evaluate the influence of embolus size on the absorption of 125I- deposited on the bronchoalveolar surface, we exposed isolated perfused rabbit lungs to an aerosol containing 125I- for 5 min. We monitored the blood radioactivity for the subsequent 2 h. Several groups of lungs were studied, including those in which blood flow was varied and those in which enough glass beads ranging in size from 58 to 548 micron were injected into the pulmonary artery to approximately double the vascular resistance. The results indicated that under control conditions approximately 94% of the 125I- deposited on the intrapulmonary bronchoalveolar surface was able to reach the pulmonary circulation during the 2-h perfusion period, and the bronchoalveolar surface was sufficiently perfused so that absorption was limited by the rate of diffusion into the blood rather than the rate of blood flow. In the absence of embolization, the initial absorption rate was approximately 10.4%/min regardless of the total flow rate. The 58-micron beads reduced the rate to approximately 7.5%/min, whereas the beads greater than or equal to 194 micron in diameter reduced the rate to approximately 4.5%/min. Thus the effect of the embolization on the absorption rate was directly related to the bead diameter, even though the number of beads injected was adjusted to produce about the same increase in vascular resistance.     

Mechanism of stimulation of pulmonary prostacyclin synthesis at birth

In order to investigate the mechanism behind ventilation-induced pulmonary prostacyclin production at birth, chloralose anesthetized, exteriorized, fetal lambs were ventilated with a gas mixture that did not change blood gases (fetal gas) and unventilated fetal lungs were perfused with blood containing increased O2 and decreased CO2. Ventilation with fetal gas (3%O2, 5%CO2) increased net pulmonary prostacyclin (as 6-keto-PGF1 alpha) production from -5.1 +/- 4.4 to +12.6 +/- 7.6 ng/kg X min. When ventilation was stopped, net pulmonary prostacyclin production returned to nondetectable levels. Ventilation with gas mixtures which increased pulmonary venous PO2 and decreased PCO2 also stimulated pulmonary prostacyclin production, but did not have greater effects than did ventilation with fetal gas. In order to determine if increasing PO2 or decreasing PCO2 could stimulate pulmonary prostacyclin production independently from ventilation, unventilated fetal lamb lungs were perfused with blood that had PO2 and PCO2 similar to fetal blood, blood with elevated O2, and blood that had PO2 and PCO2 values similar to arterial blood of newborn animals. Neither increased O2 nor decreased CO2 in the blood perfusing the lungs stimulated pulmonary prostacyclin synthesis. We conclude that the mechanism responsible for the stimulation of pulmonary prostacyclin production with the onset of ventilation at birth is tissue stress during establishment of gaseous ventilation and rhythmic ventilation.     

Alpha-adrenergic agents have little effect during air embolism lung injury in awake sheep

Since it is not clear whether alpha-adrenergic receptors can modulate lung microvascular liquid and protein leakiness, we studied the effects of alpha-adrenergic receptor stimulation or blockade on lung filtration under base-line conditions and during the acute lung injury caused by a 4-h infusion of venous air emboli in six unanesthetized, chronically instrumented sheep with lung lymph fistulas. During the experiments we continuously infused the alpha-adrenergic receptor agonist phenylephrine hydrochloride (1.0 microgram X kg-1 X min-1 iv) or the alpha-adrenergic receptor antagonist phentolamine mesylate (1.0 mg X kg-1 X min-1 iv), and we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and the lymph-to-plasma protein concentration ratio. During air embolism, alpha-receptor stimulation increased pulmonary vascular resistance and decreased lung lymph flow by 25%; alpha-receptor blockade had the opposite effects. During recovery, neither agent significantly affected pulmonary hemodynamics or lymph flow. Our results indicate that alpha-adrenergic receptors are active during air embolism and modulate pulmonary filtration by causing arteriolar constriction, which reduces the surface area or the perfusion pressure in the pulmonary microvascular bed. They may also affect venous smooth muscle tone. We found no evidence that alpha-adrenergic receptors modulate lung microvascular liquid or protein leakiness directly.     

Venous occlusion pressure and vascular permeability in the dog lung after air embolization

Pulmonary edema has frequently been associated with air embolization of the lung. In the present study the hemodynamic effects of air emboli (AE) were studied in the isolated mechanically ventilated canine right lower lung lobe (RLL), pump perfused at a constant blood flow. Air was infused via the pulmonary artery (n = 7) at 0.6 ml/min until pulmonary arterial pressure (Pa) rose 250%. While Pa rose from 12.4 +/- 0.6 to 44.6 +/- 2.0 (SE) cmH2O (P less than 0.05), venous occlusion pressure remained constant (7.0 +/- 0.5 to 6.8 +/- 0.6 cmH2O; P greater than 0.05). Lobar vascular resistance (RT) increased from 2.8 +/- 0.3 to 12.1 +/- 0.2 Torr.ml-1.min.10(-2) (P less than 0.05), whereas the venous occlusion technique used to determine the segmental distribution of vascular resistance indicated the increase in RT was confined to vessels upstream to the veins. Control lobes (n = 7) administered saline at a similar rate showed no significant hemodynamic changes. As an index of microvascular injury the pulmonary filtration coefficient (Kf) was obtained by sequential elevations of lobar vascular pressures. The Kf was 0.11 +/- 0.01 and 0.07 +/- 0.01 ml.min-1.Torr-1.100 g RLL-1 in AE and control lobes, respectively (P less than 0.05). Despite a higher Kf in AE lobes, total lobe weight gains did not differ and airway fluid was not seen in the AE group. Although air embolization caused an increase in upstream resistance and vascular permeability, venous occlusion pressure did not increase, and marked edema did not occur.     

Bubble splitting in bifurcating tubes: a model study of cardiovascular gas emboli transport.

The transport of long gas bubbles, suspended in liquid, through symmetric bifurcations, is investigated experimentally and theoretically as a model of cardiovascular gas bubble transport in air embolism and gas embolotherapy. The relevant dimensionless parameters in the models match the corresponding values for arteries and arterioles. The effects of roll angle (the angle the plane of the bifurcation makes with the horizontal), capillary number (a dimensionless indicator of flow), and bubble volume (or length) on the splitting of bubbles as they pass through the bifurcation are examined. Splitting is observed to be more homogenous at higher capillary numbers and lower roll angles. It is shown that, at nonzero roll angles, there is a critical value of the capillary number below which the bubbles do not split and are transported entirely into the upper branch. The value of the critical capillary number increases with roll angle and parent tube diameter. A unique bubble motion is observed at the critical capillary number and for slightly slower flows: the bubble begins to split, the meniscus in the lower branch then moves backward, and finally the entire bubble enters the upper branch. These findings suggest that, in large vessels, emboli tend to be transported upward unless flow is unusually strong but that a more homogeneous distribution of emboli occurs in smaller vessels. This corresponds to previous observations that air emboli tend to lodge in the upper regions of the lungs and suggests that relatively uniform infarction of tumors by gas embolotherapy may be possible.     

Application of respiratory heat exchange for the measurement of lung water.

A noninvasive method for measuring pulmonary blood flow and lung mass (called airway thermal volume), based on the measurements of lung heat exchange with environment, is described. The lungs function as a steady-state heat exchange system, having an inner heat source (pulmonary blood flow) and an external heat sink (ventilation). Sudden changes in the steady-state condition, such as caused by hyperventilation of dry air, lead to a new steady state after a few minutes. The expired air temperature difference between the initial and final steady states is proportional to pulmonary blood flow, whereas the rate at which the new steady state is achieved is proportional to airway thermal volume. The method was tested in 20 isolated dogs lungs, 9 perfused goat lungs, and 27 anesthetized sheep. The expired air temperature fall during hyperventilation was inversely proportional to the perfusion rate of the isolated lungs, and half-time of the temperature fall was proportional to the lung tissue mass. Experiments in anesthetized sheep showed that the measured airway thermal volume is close to the total mass of the excised lungs, including its residual blood (r = 0.98). Pulmonary edema and fluid instillation into the bronchial tree increased in the measured lung mass.     

Effect of high-frequency ventilation on gas exchange and pulmonary vascular resistance in lambs

We studied the effects of conventional mechanical ventilation (CMV) (15 ml/kg tidal volume delivered at 18-25 breaths/min) and high-frequency oscillatory ventilation (HFOV) (less than or equal to 2 ml/kg delivered at 10 Hz) on pulmonary hemodynamics and gas exchange during ambient air breathing and hypoxic gas breathing in 10 4-day-old lambs. After instrumentation and randomization to either HFOV or CMV the animals breathed first ambient air and then hypoxic gas (inspired O2 fraction = 0.13) for 20 min. The mode of ventilation was then changed, and the normoxic and hypoxic gas challenges were repeated. The multiple inert gas elimination technique was utilized to assess gas exchange. There was a significant increase with HFOV in mean pulmonary arterial pressure (Ppa) (20.1 +/- 4.2 vs. 22 +/- 3.8 Torr, CMV vs. HFOV, P less than 0.05) during ambient air breathing. During hypoxic gas breathing Ppa was also greater with HFOV than with CMV (29.5 +/- 5.7 vs. 34 +/- 3.1 Torr, CMV vs. HFOV, P less than 0.05). HFOV reduced pulmonary blood flow (Qp) during ambient air breathing (0.33 +/- 0.11 vs. 0.28 +/- 0.09 l . kg-1 . min-1, CMV vs. HFOV, P less than 0.05) and during hypoxic gas breathing (0.38 +/- 0.11 vs. 0.29 +/- 0.09 l . kg-1 . min-1, P less than 0.05). There was no significant difference in calculated venous admixture for sulfur hexafluoride or in the index of low ventilation-perfusion lung regions with HFOV compared with CMV.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Bimodal breathing in the estuarine crab Chasmagnathus granulatus Dana 1851--physiological and morphological studies

Chasmagnathus granulatus is an estuarine crab which actively moves from subtidal to supratidal areas. To elucidate the possible existence of extrabranchial sites for aerial gas exchange, we measured respiratory and acid-base variables in animals with and without branchial water (controls and experimental crabs, respectively) during air exposure. An histological study of the branchiostegite was also performed. Throughout 4 h of emergence C. granulatus did not suffer venous hypoxia, even without branchial water. The rate of oxygen uptake (M(O(2))) was similar in both groups. The rate of carbon dioxide excretion (M(CO(2))) and the gas exchange ratio (R) significantly decreased during emergence in both groups, with R significantly lower for experimental crabs. Consequently, CO(2) was accumulated in the hemolymph. This variable stabilized after 90 min in control animals, but experimental crabs continued accumulating CO(2). Histological study of the branchiostegites demonstrated the presence of an attenuated and greatly perfused epithelium facing the branchial chamber lumen, with a shortest diffusion distance of 0.5 microm. Simple folds and lobulated projections increase the respiratory surface area. These results suggest that C. granulatus is a bimodal breathing crab, active both in water and air. When emerged, this species extract oxygen directly from air through branchiostegal lungs, but relies on branchial exchange to eliminate carbon dioxide.     

Stratified Pulmonary Blood Flow: Some Consequences in Emphysema and Pulmonary Embolism

Both ventilation and blood flow in the secondary lobule of the lung are stratified; each unit of lung tissue in the proximal portion of the lobule receives up to four times the blood flow of units in the peripheral portion. Questions of the limiting role of gas diffusion within the small airways become virtually irrelevant in the face of this stratification of function.The central portion of the lobule, with its high ventilation, blood flow, and gas exchange, is very vulnerable; small lesions at this site will produce disproportionately large disturbances of gas exchange and of pulmonary vascular resistance. This may well account for some of the phenomena of conditions such as centrilobular emphysema and pulmonary microembolism.     

Effect of hypoxia on pulmonary blood flow-segmental vascular resistance relationship in perfused cat lungs

To investigate the effect of alveolar hypoxia onthe pulmonary blood flow-segmental vascular resistance relationship, wedetermined the longitudinal distribution of vascular resistance whileincreasing blood flow during hyperoxia or hypoxia in perfused catlungs. We measured microvascular pressures by the micropipetteservo-null method, partitioned the pulmonary vessels into threesegments [i.e., arterial (from main pulmonary artery to 30- to50-µm arterioles), venous (from 30- to 50-µm venules to leftatrium), and microvascular (between arterioles and venules)segments] and calculated segmental vascular resistance. Duringhyperoxia, total resistance decreased with increased blood flow becauseof a reduction of microvascular resistance. In contrast, duringhypoxia, not only microvascular resistance but also arterial resistancedecreased with increase of blood flow while venous resistance remainedunchanged. The reduction of arterial resistance was presumably causedby arterial distension induced by an elevated arterial pressure duringhypoxia. We conclude that, during hypoxia, both microvessels andarteries >50 µm in diameter play a role in preventing furtherincreases in total pulmonary vascular resistance with increased bloodflow.

     

Differential effects of prostaglandins A1 and A2 on pulmonary vascular resistance in the dog.

The effects of PGA1 and PGA2 were studied in the canine pulmonary vascular bed. Infusion of PGA1 into the lobar artery decreased lobar arterial and venous pressure but did not change left atrial pressure. In contrast, PGA2 infusion increased lobar arterial and venous pressure and the effects of this substance were similar in experiments in which the lung was perfused with dextran or with blood. These data indicate that under conditions of controlled blood flow PGA1 decreases pulmonary vascular resistance by dilating intrapulmonary veins and to a lesser extent vessels upstream to the small veins, presumably small arteries. The present data show that PGA2 increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream vessels. The predominant effect of PGA2 was on upstream vessels and the pressor effect was not due to interaction with formed elements in the blood or platelet aggregation.     

P-31 Nuclear Magnetic Resonance Analysis of Brain: II. Effects of Oxygen Deprivation on Isolated Perfused and Nonperfused Rat Brain

Phosphatic metabolite (perchloric acid extractable) concentrations of cerebral tissues were analyzed by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy following external perfusion of the isolated rat brain (30 min or 60 min) under the following conditions: (a) constant perfusion pressure with either fluorocarbon- or erythrocyte-based medium, and (b) constant perfusate flow rate (3 ml/min) with the erythrocyte-based medium. Metabolite concentrations of control perfused brains were compared with those in nonperfused controls to provide a basis for detecting any qualitative or quantitative changes in cerebral metabolite composition. Metabolic responses of perfused brains to ischemia (incomplete ischemia, 83% reduction in flow for 10 min; transient complete ischemia for 1.5 or 2 min) were evaluated immediately after the ischemic episode and at selected time points during reperfusion (3 and 15 min). Alterations in cerebral metabolite levels induced by hypoxia were analyzed using a nonperfused rat brain model. Irrespective of the perfusion method employed, the phosphatic metabolites of control perfused rat brains were identical quantitatively to those of the nonperfused controls. Cerebral ischemia resulted in significantly increased levels of ADP, AMP + IMP, Pi, fructose 1,6-diphosphate, and glycerol 3-phosphate (global ischemia only), whereas ATP and phosphocreatine (PCr) levels declined significantly. The magnitude of these changes varied with the severity of the ischemia; however, following 15 min of control reperfusion metabolite levels had reverted to preischemic values. Significant perturbations in tissue phosphoethanolamine (3.84 delta resonance) content were evident at various time points during ischemia and postischemic recovery, which varied according to the perfusion conditions. In contrast to the changes observed in response to ischemia, hypoxia affected only cerebral high-energy phosphate levels. ATP and PCr levels were reduced, while a concomitant, essentially equimolar, increase in Pi and ADP was observed. The present studies indicate that in terms of phosphatic metabolites, the control equilibrated isolated perfused rat brain is quantitatively and qualitatively indistinguishable from the nonperfused rat brain in vivo regardless of the perfusion conditions (constant flow versus constant pressure). The metabolic responses to ischemia and hypoxia, as measured by P-31 NMR, were consistent with the pattern of changes reported elsewhere. Overall, P-31 NMR spectroscopic evaluation of the intact rat brain provides a potential experimental context for dynamic measures of cerebral metabolism under exogenously controlled conditions. Th     

Direct demonstration of 25- and 50-microm arteriovenous pathways in healthy human and baboon lungs

Postmortem microsphere studies in adult human lungs have demonstrated the existence of intrapulmonary arteriovenous pathways using nonphysiological conditions. The aim of the current study was to determine whether large diameter (>25 and 50 microm) intrapulmonary arteriovenous pathways are functional in human and baboon lungs under physiological perfusion and ventilation pressures. We used fresh healthy human donor lungs obtained for transplantation and fresh lungs from baboons (Papio c. anubis). Lungs were ventilated with room air by using a peak inflation pressure of 15 cm H(2)O and a positive end-expiratory pressure of 5 cm H(2)O. Lungs were perfused between 10 and 20 cm H(2)O by using a phosphate-buffered saline solution with 5% albumin. We infused a mixture of 25- and 50-microm microspheres (0.5 and 1 million total for baboons and human studies, respectively) into the pulmonary artery and collected the entire pulmonary venous outflow. Under these conditions, evidence of intrapulmonary arteriovenous anastomoses was found in baboon (n = 3/4) and human (n = 4/6) lungs. In those lungs showing evidence of arteriovenous pathways, 50-microm microspheres were always able to traverse the pulmonary circulation, and the fraction of transpulmonary passage ranged from 0.0003 to 0.42%. These data show that intrapulmonary arteriovenous pathways >50 microm in diameter are functional under physiological ventilation and perfusion pressures in the isolated lung. These pathways provide an alternative conduit for pulmonary blood flow that likely bypasses the areas of gas exchange at the capillary-alveolar interface that could compromise both gas exchange and the ability of the lung to filter out microemboli.     

Blood flow in exercising muscles by xenon clearance and by microsphere trapping

The accuracy of muscle blood flow measurement by the 133Xe clearance method (QXe) was assessed against direct venous outflow (Qv) and microsphere trapping flow (Q mu) determinations in isolated perfused dog gastrocnemius both at rest and during graded stimulation [O2 consumption (VO2) up to 12 ml X 100 g-1 X min-1] and in the gastrocnemius, vastus lateralis, and triceps of intact dogs at rest and while running on a treadmill at varied speeds up to maximum VO2. In 29 measurements performed in 11 isolated muscles, Q mu was in good agreement with Qv at rest and at all stimulation levels (Q mu/Qv = 1.0; r = 0.98). 133Xe clearance yielded much lower blood flows than the venous outflow and the microsphere trapping methods. In 43 measurements in 11 muscles, the mean QXe/Qv ratio was 0.57 +/- 0.03 (SE), independent of blood flow. Similarly, in 65 measurements in 2 intact dogs, the mean QXe/Q mu ratio in all tested muscles was 0.49 +/- 0.02 (SE), independent of blood flow. These results show that the 133Xe clearance method considerably underestimates blood flow in dog muscles.     

Influence of lung volume and left atrial pressure on reverse pulmonary venous blood flow

Infarction of the lung is uncommon even when both the pulmonary and the bronchial blood supplies are interrupted. We studied the possibility that a tidal reverse pulmonary venous flow is driven by the alternating distension and compression of alveolar and extra-alveolar vessels with the lung volume changes of breathing and also that a pulsatile reverse flow is caused by left atrial pressure transients. We infused SF6, a relatively insoluble inert gas, into the left atrium of anesthetized goats in which we had interrupted the left pulmonary artery and the bronchial circulation. SF6 was measured in the left lung exhalate as a reflection of the reverse pulmonary venous flow. No SF6 was exhaled when the pulmonary veins were occluded. SF6 was exhaled in increasing amounts as left atrial pressure, tidal volume, and ventilatory rates rose during mechanical ventilation. SF6 was not excreted when we increased left atrial pressure transients by causing mitral insufficiency in the absence of lung volume changes (continuous flow ventilation). Markers injected into the left atrial blood reached the alveolar capillaries. We conclude that reverse pulmonary venous flow is driven by tidal ventilation but not by left atrial pressure transients. It reaches the alveoli and could nourish the alveolar tissues when there is no inflow of arterial blood.