Hypoxemia increases renin secretion rate in anesthetized newborn lambs

The response of renin secretion rate (RSR) to acute systemic hypoxemia (mean arterial p0₂ 34±8 torr) was studied in mechanically ventilated, anesthetized newborn lambs 5–10 days of age (n=6). Ventilation of these lambs with room air (normoxemia) was followed by administration of low oxygen inhaled gas mixture (f_i0₂ 0.11) which was associated with no change in arterial pC0₂, pH, mean arterial pressure (MAP), renal blood flow (RBF, measured by electromagnetic flow probe), and calculated renal vascular resistance (RVR). Arterial plasma renin activity (PRA_A 4.28±1.73 to 6.46±3.00 ng AI/ml · hr), renal vein plasma renin activity (PRA_RV, 6.26±3.79 to 11.44±7.11 ng AI/ml · hr) and renin secretion rate (RSR, 19.86±21.70 to 51.32±48.54 units/min · KgBW) increased significantly (p<0.05) in response to hypoxemia. Restoration of normoxemia (arterial p0₂ 100±18 torr) was associated with significant decline in MAP (to 65±14 mmHg) and RBF (to 9.0±2.1 ml/min · KgBW) and further increases in PRA_A (to 8.98±3.40 ng AI/ml · hr), PRA_RV (to 19.04±10.62 ng AI/ml · hr) and RSR (to 88.6±77.6 units/min · KgBW). PRA_A correlated strongly with PRA_RV (r=0.84) and RSR (r=0.60) in these lambs. These results suggest that PRA_A, PRA_RV and RSR increase in response to hypoxemia in anesthetized lambs by a mechanism other than renal arterial baroreceptor stimulation, although this mechanism may be active during recovery from hypoxemia. Furthermore, PRA_A closely approximates RSR in newborn lambs under these conditions.     

Laryngeal response to nasal ventilation in nonsedated newborn lambs.

Although endoscopic studies in adult humans have suggested that laryngeal closure can limit alveolar ventilation during nasal intermittent positive pressure ventilation (nIPPV), there are no available data regarding glottal muscle activity during nIPPV. In addition, laryngeal behavior during nIPPV has not been investigated in neonates. The aim of the present study was to assess laryngeal muscle response to nIPPV in nonsedated newborn lambs. Nine newborn lambs were instrumented for recording states of alertness, electrical activity [electromyograph (EMG)] of glottal constrictor (thyroarytenoid, TA) and dilator (cricothyroid, CT) muscles, EMG of the diaphragm (Dia), and mask and tracheal pressures. nIPPV in pressure support (PS) and volume control (VC) modes was delivered to the lambs via a nasal mask. Results show that increasing nIPPV during wakefulness and quiet sleep led to a progressive disappearance of Dia and CT EMG and to the appearance and subsequent increase in TA EMG during inspiration, together with an increase in trans-upper airway pressure (TUAP). On rare occasions, transmission of nIPPV through the glottis was prevented by complete, active glottal closure, a phenomenon more frequent during active sleep epochs, when irregular bursts of TA EMG were observed. In conclusion, results of the present study suggest that active glottal closure develops with nIPPV in nonsedated lambs, especially in the VC mode. Our observations further suggest that such closure can limit lung ventilation when raising nIPPV in neonates.     

Lung overexpansion increases pulmonary microvascular protein permeability in young lambs

To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Level of ventilation influences the cardiovascular response to hypoxemia in lambs

Newborn animals of a number of species display a brisk increase in ventilation followed by a gradual drop toward or below baseline within minutes of exposure to acute hypoxemia. Heart rate and cardiac output (a determinant of systemic oxygen transport along with the arterial oxygen content) appear to follow a similar pattern, but whether or not the cardiovascular response is influenced by the respiratory response is unknown. We therefore carried out experiments in which the level of ventilation was controlled during normoxemia and hypoxemia to test the hypothesis that the level of ventilation influences the cardiovascular response to acute hypoxemia. Six lambs ranging in age from 17 to 22 days were anesthetized, tracheostomized, and instrumented for measurement of cardiovascular variables. A recovery period of at least 3 days was allowed before the study when each lamb was artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen in nitrogen. A control respiratory frequency (f) of 30 breaths per min was set and a control tidal volume (VT) was chosen to achieve normocapnia. Cardiovascular measurements were made during normoxemia and hypoxemia (FIO2 0.10) 5 min after f or VT was changed to simulate a decrease, no change, or an increase in ventilation. During normoxemia, the level of ventilation had little effect on the measured cardiovascular variables. At control levels of ventilation, hypoxemia caused an increase in cardiac output that was due solely to an increase in stroke volume as heart rate decreased; blood pressure was unchanged. Increasing ventilation during hypoxemia did not augment cardiac output or alter blood pressure as compared with that observed at control levels of ventilation. Decreasing ventilation during hypoxemia, however, decreased cardiac output due to a profound bradycardia; blood pressure increased significantly. Our data provide evidence that the level of ventilation significantly influences the cardiovascular response to hypoxemia in young lambs.     

Meclofenamate does not affect lung development in fetal sheep

Prostaglandins may be involved in some aspects of fetal lung development, including surfactant metabolism, tracheal fluid production, and possibly lung growth. In the fetus, during the days before delivery, plasma PGE2 concentration increases and concurrently, tracheal fluid production decreases and surfactant production increases. To determine whether the increase in PGE2, specifically plasma PGE2 concentration, is responsible for these changes, we continuously infused the prostaglandin synthetase inhibitor, meclofenamate (0.7 mg/h per kg), into 8 fetal sheep for 5-13 days before delivery; 5 control fetuses received a continuous infusion of solvent for 5-11 days before delivery. Meclofenamate infusion significantly decreased plasma PGE2 concentrations until the day of delivery. However, meclofenamate did not affect tracheal fluid production or its decrease before delivery, fetal plasma cortisol concentration, surfactant content of tracheal fluid and lung tissue, organ weights, lung weights, or lung DNA and protein content. We conclude that the changes in lung development during the days before delivery are not dependent on the usual high fetal plasma concentration of PGE2 or its increase before delivery.     

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.     

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)     

High-frequency oscillatory ventilation increases canine pulmonary epithelial permeability

To investigate the effect of high-frequency oscillatory ventilation (HFOV) on the pulmonary epithelial permeability, we measured the clearance rate of nebulized sodium pertechnetate (99mTcO4-) and diethylenetriaminepentaacetate (99mTc-DTPA) before and after a 4-h period of mechanical ventilation in anesthetized mongrel dogs. The animals also underwent experiments with 4 h of spontaneous breathing (SB) and intermittent positive-pressure ventilation (IPPV) with and without addition of positive end-expiratory pressure (PEEP) for comparison. After IPPV and SB there was no change in the clearance rate of either 99mTcO4- or 99mTc-DTPA. After IPPV + PEEP and HPOV (8 and 16 Hz), there was an increase in the clearance rate of 99mTc-DTPA, but an increase in clearance rate of 99mTcO4- was seen after IPPV + PEEP only. In a separate group of dogs an increase in end-tidal lung volume was demonstrated after 4 h of ventilation with IPPV + PEEP (but not after HFOV), and this may account for the measured increase in 99mTcO4- clearance. We conclude that an increase in 99mTc-DTPA clearance rate after HFOV signifies an increase in pulmonary epithelial permeability, possibly through the mechanism of damage to the intercellular junctions during HFOV.     

Dopamine increases lung liquid clearance during mechanical ventilation

Short-term mechanical ventilation with high tidal volume (HVT) causes mild to moderate lung injury and impairs active Na+ transport and lung liquid clearance in rats. Dopamine (DA) enhances active Na+ transport in normal rat lungs by increasing Na+-K+-ATPase activity in the alveolar epithelium. We examined whether DA would increase alveolar fluid reabsorption in rats ventilated with HVT for 40 min compared with those ventilated with low tidal volume (LVT) and with nonventilated rats. Similar to previous reports, HVT ventilation decreased alveolar fluid reabsorption by ~50% (P < 0.001). DA increased alveolar fluid reabsorption in nonventilated control rats (by ~60%), LVT ventilated rats (by approximately 55%), and HVT ventilated rats (by ~200%). In parallel studies, DA increased Na+-K+-ATPase activity in cultured rat alveolar epithelial type II cells (ATII). Depolymerization of cellular microtubules by colchicine inhibited the effect of DA on HVT ventilated rats as well as on Na+-K+-ATPase activity in ATII cells. Neither DA nor colchicine affected the short-term Na+-K+-ATPase alpha1- and beta1-subunit mRNA steady-state levels or total alpha1- and beta1-subunit protein abundance in ATII cells. Thus we reason that DA improved alveolar fluid reabsorption in rats ventilated with HVT by upregulating the Na+-K+-ATPase function in alveolar epithelial cells.     

Effects of sleep-induced increases in upper airway resistance on ventilation

To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aerosol anesthesia increases hypercapnic ventilation and breathlessness in laryngectomized humans

The effect of local anesthetic aerosol inhalation on the ventilatory response and the sensation of breathlessness to CO2 rebreathing was studied in seven healthy male subjects with permanent tracheal stomas after laryngectomy for carcinoma. Inhalation of bupivacaine aerosol sufficient to abolish the cough reflex to mechanical probing below the carina increased the ventilatory response to CO2 in six of seven subjects compared with saline control. This was achieved by an increase in both respiratory frequency (f) and tidal volume (VT) in four subjects, f in one subject, and VT in one subject. All subjects reported that they were more breathless on rebreathing after bupivacaine aerosol. The six subjects who recorded breathlessness with a visual analog scale (VAS) indicated its onset at a lower minute ventilation (VE) and gave higher VAS scores for equivalent levels of VE after threshold. We conclude that the enhanced CO2 sensitivity and breathlessness on rebreathing after airway anesthesia results from altered lower airway receptor discharge.     

Effects of duration of positive-pressure ventilation on blood-brain barrier function in premature lambs.

We have been studying the ontogeny of the blood-brain barrier function in ovine fetuses and lambs. During these studies, we have found that the duration of ventilation also influences blood-brain barrier permeability in premature lambs. Chronically instrumented hysterotomy-delivered surfactant-treated premature lambs were studied at 90% or 137 days of gestation (n = 9). Blood-brain barrier function was quantified with the blood-to-brain transfer constant K(i) to alpha-aminoisobutyric acid. Linear regression analysis was used to compare the K(i) values in the brain regions, as the dependent variable, to the duration of ventilation, as the independent variable. There were direct correlations (P < 0.05) between the K(i) values and the duration of ventilation [306 min (mean), 162-474 min (range)] in the cerebral cortex, cerebellum, medulla, caudate nucleus, hippocampus, superior colliculus, inferior colliculus, thalamus, pons, cervical spinal cord, and choroid plexus, but not in the pituitary gland. Ventilatory pressures and rates were established before the onset of the permeability studies. Calculated mean airway pressures [14 cmH(2)O (mean), 7-20 cmH(2)O (range)] from similarly studied premature lambs did not correlate with the duration of positive-pressure ventilation. We conclude that increases in the duration of positive-pressure ventilation predispose premature lambs to increases in regional blood-brain barrier permeability. These alterations in barrier function occur over relatively short time intervals (minutes to hours). In our study, these changes in permeability are most likely not attributable to changes in mean airway pressure.     

Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide generation in lambs with surgically induced acute increases in pulmonary blood flow

We have previously shown that acute increases in pulmonary blood flow (PBF) are limited by a compensatory increase in pulmonary vascular resistance (PVR) via an endothelin‐1 (ET‐1) dependent decrease in nitric oxide synthase (NOS) activity. The mechanisms underlying the reduction in NO signaling are unresolved. Thus, the purpose of this study was to elucidate mechanisms of this ET‐1–NO interaction. Pulmonary arterial endothelial cells were acutely exposed to shear stress in the presence or absence of tezosentan, a combined ET_A/ET_B receptor antagonist. Shear increased NO_x, eNOS phospho‐Ser1177, and H₂O₂ and decreased catalase activity; tezosentan enhanced, while ET‐1 attenuated all of these changes. In addition, ET‐1 increased eNOS phospho‐Thr495 levels. In lambs, 4 h of increased PBF decreased H₂O₂, eNOS phospho‐Ser1177, and NO_X levels, and increased eNOS phospho‐Thr495, phospho‐catalase, and catalase activity. These changes were reversed by tezosentan. PEG‐catalase reversed the positive effects of tezosentan on NO signaling. In all groups, opening the shunt resulted in a rapid increase in PBF by 30 min. In vehicle‐ and tezosentan/PEG‐catalase lambs, PBF did not change further over the 4 h study period. PVR fell by 30 min in vehicle‐ and tezosentan‐treated lambs, and by 60 min in tezosentan/PEG‐catalase‐treated lambs. In vehicle‐ and tezosentan/PEG‐catalase lambs, PVR did not change further over the 4 h study period. In tezosentan‐treated lambs, PBF continued to increase and LPVR to decrease over the 4 h study period. We conclude that acute increases in PBF are limited by an ET‐1 dependent decrease in NO production via alterations in catalase activity, H₂O₂ levels, and eNOS phosphorylation. J. Cell. Biochem. 114: 435–447, 2013. © 2012 Wiley Periodicals, Inc.     

Tidal volume effects on surfactant treatment responses with the initiation of ventilation in preterm lambs

Wada, Kazuko, Alan H. Jobe, and Machiko Ikegami. Tidalvolume effects on surfactant treatment responses with the initiation ofventilation in preterm lambs. J. Appl.Physiol. 83(4): 1054-1061, 1997.We hypothesizedthat initiation of ventilation in preterm lambs with high volumes wouldcause lung injury and decrease the subsequent response to surfactanttreatment. Preterm lambs were randomized to ventilation for 30 minafter birth with 5 ml/kg (VT5),10 ml/kg (VT10), or 20 ml/kg(VT20) tidal volumes and then ventilated with ~10 ml/kg tidal volumes to achieve arterialPCO₂ values of ~50 Torr to 6 h ofage. VT20 lambs had lowercompliances, lower ventilatory efficiencies, higher recoveries ofprotein, and lower recoveries of surfactant in alveolar lavages and in surfactant that had decreased compliances when tested in preterm rabbits than VT5 orVT10 lambs. Other lambsrandomized to treatment with surfactant at birth and ventilation with6, 12, or 20 ml/kg tidal volumes for 30 min had no indicators of lunginjury. An initial tidal volume of 20 ml/kg decreased the subsequentresponse to surfactant treatment, an effect that was prevented withsurfactant treatment at birth.

     

Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs

Several congenital heart defects require surgery that acutely increases pulmonary blood flow (PBF). This can lead to dynamic alterations in postoperative pulmonary vascular resistance (PVR) and can contribute to morbidity and mortality. Thus the objective of this study was to determine the role of nitric oxide (NO), endothelin (ET)-1, and their interactions in the alterations of PVR after surgically induced increases in PBF. Twenty lambs underwent placement of an aortopulmonary vascular graft. Lambs were instrumented to measure vascular pressures and PBF and studied for 4 h. Before and after shunt opening, lambs received an infusion of saline (n = 9), tezosentan, an ETA- and ETB -receptor antagonist (n = 6), or Nomega-nitro-L-arginine (L-NNA), a NO synthase (NOS) inhibitor (n = 5). In control lambs, shunt opening increased PBF by 117.8% and decreased PVR by 40.7% (P < 0.05) by 15 min, without further changes thereafter. Plasma ET-1 levels increased 17.6% (P < 0.05), and total NOS activity decreased 61.1% (P < 0.05) at 4 h. ET-receptor blockade (tezosentan) prevented the plateau of PBF and PVR, such that PBF was increased and PVR was decreased compared with controls at 3 and 4 h (P < 0.05). These changes were associated with an increase in total NOS activity (+61.4%; P < 0.05) at 4 h. NOS inhibition (L-NNA) after shunt placement prevented the sustained decrease in PVR seen in control lambs. In these lambs, PVR decreased by 15 min (P < 0.05) but returned to baseline by 2 h. Together, these data suggest that surgically induced increases in PBF are limited by vasoconstriction, at least in part by an ET-receptor-mediated decrease in lung NOS activity. Thus NO appears to be important in maintaining a reduction in PVR after acutely increased PBF.     

EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs.

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs and oxygenation. Inhibition of prostaglandin synthesis prevents pulmonary vasodilation during rhythmic distension of the lungs but not during oxygenation. Because endothelium-derived relaxing factor (EDRF) modulates pulmonary vascular tone at birth, at rest, and during hypoxia in older animals, we hypothesized that EDRF may modulate pulmonary vascular tone during oxygenation in fetal lambs. We studied the responses to N omega-nitro-L-arginine, a competitive inhibitor of EDRF synthesis, in nine near-term fetal lambs and to drug vehicle in six of these lambs and the subsequent responses to in utero ventilation with 95% O2 in these fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by meclofenamate. N omega-nitro-L-arginine increased pulmonary and systemic arterial pressures by 28% (P < 0.05) and 31% (P < 0.05), respectively, and decreased pulmonary blood flow by 83% (P < 0.05). In the controls, ventilation with 95% O2 increased pulmonary blood flow by 1,050% (P = 0.05) without changing pressures, thereby decreasing pulmonary vascular resistance by 88% (P = 0.05). During N omega-nitro-L-arginine infusion, ventilation with 95% O2 increased pulmonary blood flow by 162% (P = 0.05) and decreased pulmonary vascular resistance by 74% (P = 0.05). This suggests that EDRF may play an important role in modulating resting pulmonary vascular tone in fetal lambs and in the vasodilatory response to ventilation with O2 in utero.     

Partial liquid ventilation improves gas exchange and increases EELV in acute lung injury

Gas exchange is improved during partial liquidventilation with perfluorocarbon in animal models of acute lung injury.The specific mechanisms are unproved. We measured end-expiratory lung volume (EELV) by null-point body plethysmography in anesthetized sheep.Measurements of gas exchange and EELV were made before and after acutelung injury was induced with intravenous oleic acid to decrease EELVand worsen gas exchange. Measurements of gas exchange and EELV wereagain performed after partial liquid ventilation with 30 ml/kg ofperfluorocarbon and compared with gas-ventilated controls. Oxygenationwas significantly improved during partial liquid ventilation, and EELV(composite of gas and liquid) was significantly increased, comparedwith preliquid ventilation values and gas-ventilated controls. Weconclude that partial liquid ventilation may directly recruitconsolidated alveoli in the lung-injured sheep and that this may be onemechanism whereby gas exchange is improved.