Role of ventilation strategy on perfluorochemical evaporation from the lungs.

To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2), VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant VE and adjusted tidal volume. PFC content in the expired gas was measured, and E(L) was calculated. There was a significant VE- and time-dependent effect on E(L.) Initially, percent PFC saturation and loss rate decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For the groups at constant VE, there was a significant time effect on E(L) but no RR effect. In conclusion, E(L) profile is dependent on VE with little effect of the RR-tidal volume combination. Thus measurement of E(L) and VE should be considered for the replacement dosing schemes during partial liquid ventilation.     

In vitro cellular effects of perfluorochemicals correlate with their lipid solubility

Preclinical studies comparing perflubron partial liquid ventilation with conventional mechanical ventilation have indicated that perflubron partial liquid ventilation may exert some anti-inflammatory effects. To assess whether these effects were related to the lipid solubility properties of perflubron rather than to nonspecific biophysical properties of the perfluorocarbon (PFC) liquid phase, we studied the effects of PFCs with varying lipid solubilities on the platelet aggregation response to various procoagulants and the erythrocyte hemolytic response to osmotic stress. In both cases, the degree of the response was directly related to the lipid solubility of the PFC. All the perflubron content of erythrocytes was found to be associated with the membrane compartment. The time to reach a maximum effect on hemolysis with perflubron was relatively slow (2-4 h), which paralleled the time for perflubron to accumulate in erythrocyte membranes. The rate and extent of perflubron partitioning into lecithin liposomes were similar to those of erythrocyte membranes, supporting the hypothesis that perflubron was partitioning into the lipid component of the membranes. Thus some of the potential modulatory effects of perflubron on excessive inflammatory responses that occur during acute lung injury and acute respiratory distress syndrome may be influenced in part by the extent of PFC partitioning into the lipid bilayers of cellular membranes.     

Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency

Wolfson, Marla R., Nancy E. Kechner, Robert F. Roache,Jean-Pierre DeChadarevian, Helena E. Friss, S. David Rubenstein, andThomas H. Shaffer. Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency. J. Appl. Physiol. 84(2): 624-640, 1998.To test the hypotheses that perfluorochemical (PFC) liquidrescue after natural surfactant (SF) treatment would improve pulmonaryfunction and histology and that this profile would be influenced by PFCdose or ventilator strategy, anesthetized preterm lambs(n = 31) with respiratory distresswere studied using nonpreoxygenated perflubron. All animals received SFat 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventionalmechanical gas ventilation (n = 8),2) 30 ml/kg perflubron with gasventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8),3) 10 ml/kg perflubron with PLV at60 breaths/min (n = 7), and4) 10 ml/kg perflubron with PLV at30 breaths/min (n = 8). All animalstolerated instillation without additional cardiopulmonary instability.All perflubron-rescued groups demonstrated sustained improvement in gasexchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement wasdirectly related to perflubron dose and breathing frequency; peakinspiratory pressure required to achieve physiological gas exchange waslower in the higher-dose and -frequency groups, and mean airwaypressure was lower in the lower-frequency group. Lung expansion wasgreater and evidence of barotrauma was less in the higher-dose and-frequency group; regional differences in expansion were not differentas a function of dose but were greater in the lower-frequency group.Regional differences in lung perflubron content were reduced in thehigher-dose and -frequency groups and greatest in the lower-dose and-frequency group. The results suggest that, whereas PLV of theSF-treated lung improves gas exchange and lung mechanics, theprotective benefits of perflubron in the lung may depend on dose andventilator strategy to optimize PFC distribution and minimize exposureof the alveolar-capillary membrane to a gas-liquid interface.

     

A supervisor for volume-controlled tidal liquid ventilator using independent piston pumps

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions and lavage of inflammatory debris. This paper presents the control of a total liquid ventilator (TLV) dedicated to ventilate patients with completely filled lungs with a tidal volume of perfluorochemical liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy FRC modifications during ventilation. The prototype was tested on eight healthy term newborn lambs (<5 days old).     

Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function.

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial PO(2) (Pa(O(2))) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased Pa(O(2)), which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher Pa(O(2)), and lower arterial PCO(2) than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.     

Analysis of perfluorochemical elimination from the respiratory system

Shaffer, Thomas H., Raymond Foust IIII, Marla R. Wolfson,and Thomas F. Miller, Jr. Analysis of perfluorochemicalelimination from the respiratory system. J. Appl.Physiol. 83(3): 1033-1040, 1997.We describe asimple apparatus for analysis of perfluorochemicals (PFC) in expiredgas and thus a means for determining PFC vapor and liquid eliminationfrom the respiratory system. The apparatus and data analysis are basedon thermal conduction and mass transfer principles of gases. In vitrostudies were conducted with the PFC vapor analyzer to determinecalibration curves for output voltage as a function of individualrespiratory gases, respiratory gases saturated with PFC vapor, andvolume percent standards for percent PFC saturation (%PFC-Sat) in air.Voltage-concentration data for %PFC-Sat of the vapor from the in vitrotests were accurate to within 2.0% from 0 to 100% PFC-Sat, linear(r = 0.99, P < 0.001), and highly reproducible.Calculated volume loss of PFC liquid over time correlated well withactual loss by weight (r = 0.99, P < 0.001). In vivo studies withneonatal lambs demonstrated that PFC volume loss and evaporation ratesdecreased nonlinearly as a function of time. These relationships weremodulated by changes in PFC physical properties, minute ventilation,and postural repositioning. The results of this study demonstrate thesensitivity and accuracy of an on-line method for PFC analysis ofexpired gas and describe how it may be useful in liquid-assistedventilation procedures for determining PFC volume loss, evaporationrate, and optimum dosing and ventilation strategy.

     

Extended high-frequency partial liquid ventilation in lung injury: gas exchange, injury quantification, and vapor loss.

High-frequency oscillatory ventilation with perflubron (PFB) reportedly improves pulmonary mechanics and gas exchange and attenuates lung injury. We explored PFB evaporative loss kinetics, intrapulmonary PFB distribution, and dosing strategies during 15 h of high-frequency oscillation (HFO)-partial liquid ventilation (PLV). After saline lavage lung injury, 15 swine were rescued with high-frequency oscillatory ventilation (n = 5), or in addition received 10 ml/kg PFB delivered to dependent lung [n = 5, PLV-compartmented (PLV(C))] or 10 ml/kg distributed uniformly within the lung [n = 5, PLV(U)]. In the PLV(C) group, PFB vapor loss was replaced. ANOVA revealed an unsustained improvement in oxygenation index in the PLV(U) group (P = 0.04); the reduction in oxygenation index correlated with PFB losses. Although tissue myeloperoxidase activity was reduced globally by HFO-PLV (P < 0.01) and regional lung injury scores (lung injury scores) in dependent lung were improved (P = 0.05), global lung injury scores were improved by HFO-PLV (P < 0.05) only in atelectasis, edema, and alveolar distension but not in cumulative score. In our model, markers of inflammation and lung injury were attenuated by HFO-PLV, and it appears that uniform intrapulmonary PFB distribution optimized gas exchange during HFO-PLV; additionally, monitoring PFB evaporative loss appears necessary to stabilize intrapulmonary PFB volume.     

Perflubron attenuates neutrophil adhesion to activated endothelial cells in vitro

Infiltration of activated neutrophils into the lung appears to be a key element in the severe lung injury that develops in animal models of acute lung injury. Partial liquid ventilation with perflubron has been shown to ameliorate tissue damage compared with conventional mechanical ventilation in acute lung injury models. Pilot experiments indicated that indirect exposure to perflubron could modulate the degree to which subsequent neutrophil binding to endothelial cell monolayers was upregulated after lipopolysaccharide activation. Endothelial cell monolayers preexposed to perflubron showed >40% reductions in the surface steady-state levels of E-selectin and intercellular adhesion molecule-1 achieved after proinflammatory activation (P < 0.05), which correlated with a reduction in the real-time association constants measured by biosensor techniques. These results indicate that direct contact with the perflubron liquid phase is not necessary to attenuate inflammatory responses. Rather, diffusion of perflubron from the alveolar space into the adjacent pulmonary vascular endothelial layer may modulate neutrophil adhesion and thereby reduce the rate of infiltration of activated neutrophils into the injured lung.     

High tidal volume ventilation induces NOS2 and impairs cAMP- dependent air space fluid clearance

Tidal volume reduction during mechanical ventilation reduces mortality in patients with acute lung injury and the acute respiratory distress syndrome. To determine the mechanisms underlying the protective effect of low tidal volume ventilation, we studied the time course and reversibility of ventilator-induced changes in permeability and distal air space edema fluid clearance in a rat model of ventilator-induced lung injury. Anesthetized rats were ventilated with a high tidal volume (30 ml/kg) or with a high tidal volume followed by ventilation with a low tidal volume of 6 ml/kg. Endothelial and epithelial protein permeability were significantly increased after high tidal volume ventilation but returned to baseline levels when tidal volume was reduced. The basal distal air space fluid clearance (AFC) rate decreased by 43% (P < 0.05) after 1 h of high tidal volume but returned to the preventilation rate 2 h after tidal volume was reduced. Not all of the effects of high tidal volume ventilation were reversible. The cAMP-dependent AFC rate after 1 h of 30 ml/kg ventilation was significantly reduced and was not restored when tidal volume was reduced. High tidal volume ventilation also increased lung inducible nitric oxide synthase (NOS2) expression and air space total nitrite at 3 h. Inhibition of NOS2 activity preserved cAMP-dependent AFC. Because air space edema fluid inactivates surfactant and reduces ventilated lung volume, the reduction of cAMP-dependent AFC by reactive nitrogen species may be an important mechanism of clinical ventilator-associated lung injury.     

Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ

Treatmentsavailable to improve compliance in surfactant-deficient states includeexogenous surfactant (ES) and either partial (PLV) or total liquidventilation (TLV) with perfluorochemical (PFC). Because of theadditional air-lung and air-PFC interfaces introduced during PLVcompared with TLV, we hypothesized that compliance would be worseduring PLV than during TLV. Because surfactant is able to reduceinterfacial tension between air and lung as well as between PFC andlung, we further hypothesized that compliance would improve withsurfactant treatment before PLV. In excised preterm lamb lungs, we usedSurvanta for surfactant replacement and perflubron as the PFC.Compliance during PLV was intermediate between TLV and gas inflation,both with and without surfactant. Surfactant improved compliance duringPLV, compared with PLV alone. Because of the force-balance equationgoverning the behavior of immiscible droplets on liquid surfaces, wepredict that PFC droplets spread during PLV to cover the alveolarsurface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets insurfactant-sufficient lungs, except at end inspiration.

     

Effects of increased ventilation on lung lymph flow in unanesthetized sheep

To determine the effect of an increase in spontaneous minute ventilation on lung fluid balance, we added external dead space to the breathing circuit of six tracheostomized, unanesthetized, spontaneously breathing sheep in which lung lymph fistulas had been created surgically. The addition of 120-180 ml of dead space caused minute ventilation to increase by 50-100% (secondary to increases in both tidal volume and frequency), without changing pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, or arterial blood gas tensions. The increase in spontaneous ventilation was associated with an average increase of 27% in lung lymph flow (P less than 0.05) and an average reduction of 11% in the lymph-to-plasma concentration ratio (L/P) for total protein (P less than 0.05). Lymph flow and L/P for total protein approached stable values after 2-3 h of hyperpnea, and the increase in lymph flow persisted for at least 18 h of dead-space breathing. Removal of dead space was associated with a rapid return (within 45 min) of lymph flow to base-line levels. These results suggest that hyperpnea increases the pulmonary transvascular filtration rate. Since no changes in vascular pressures or cardiac output were observed, this increase in transvascular filtration is most likely due to a fall in interstitial fluid pressure.     

Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates.

To differentiate the effects of gas and liquid ventilation on cardiopulmonary function during early development, we compared the clinical, physiological, and histological profiles of gas- and liquid-ventilated preterm lambs (n = 16; 108-116 days gestation). Immediately after cesarean section delivery, ventilation commenced using gas delivered by a volume ventilator (n = 9) or liquid perfluorochemical (n = 7) delivered by a mechanically assisted liquid ventilation system. Pulmonary gas exchange, acid-base status, vital signs, and respiratory compliance were assessed during the 3-h protocol; sections of the lungs were obtained for histological analyses when the animals were killed. Six of nine gas-ventilated lambs expired from respiratory failure before 3 h, with the remaining animals experiencing severe respiratory insufficiency, pneumothoraces, and cardiovascular deterioration. Six of seven liquid-ventilated lambs survived with good gas exchange and cardiovascular stability and without fluorothorax; one experienced ventricular fibrillation before 1 h and expired despite pulmonary stability. Respiratory compliance was significantly greater in the liquid- than in the gas-ventilated lambs. Histological analyses of gas-ventilated lungs demonstrated nonhomogeneous lung expansion, with thick-walled gas exchange spaces containing proteinaceous exudate, hemorrhage, and hyaline membranes. In contrast, liquid-ventilated lungs appeared clear, with thin-walled and uniformly expanded gas exchange spaces that were free of hyaline membranes and luminal debris. Morphometric analyses demonstrated that surface area and gas exchange index were greater in the liquid- than in the gas-ventilated lambs. These results indicate that elimination of surface active forces by liquid ventilation during early development provides more effective gas exchange with less barotrauma compared with gas ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

An assessment of dead space in pulmonary ventilation of the toad Bufo schneideri

The respiratory cycles of Rana and Bufo has been disputed in relation to flow patterns and to the respiratory dead-space of the buccal volume. A small tidal volume combined with a much larger buccal space motivated the "jet steam" model that predicts a coherent expired flow within the dorsal part of the buccal space. Some other studies indicate an extensive mixing of lung gas within the buccal volume. In Bufo schneideri, we measured arterial, end-tidal and intrapulmonary PCO(2) to evaluate dead-space by the Bohr equation. Dead-space was also estimated as: V(D)=(total ventilation-effective ventilation)/f(R), where total ventilation and f(R) were measured by pneumotachography, while effective ventilation was derived from the alveolar ventilation equation. These approaches were consistent with a dead space of 30-40% of tidal volume, which indicates a specific pathway for the expired lung gas.     

Alveolar liquid pressure in excised edematous dog lung with increased static recoil

Alveolar liquid pressure (Pliq) was measured by micropipettes in conjunction with a servo-nulling pressure measuring system in isolated air-inflated edematous dog lungs. Pliq was measured in lungs either washed with a detergent (0.01% Triton X-100) or subjected to refrigeration for 2-3 days followed by ventilation for 3 h. At 55% of total lung capacity (TLC, the volume at a transpulmonary pressure (Ptp) of 25 cmH2O before treatment), in both the Triton-washed and the ventilated lung, Ptp increased from 5 to 11 cmH2O, whereas Pliq, decreased from -3 to -11 cmH2O relative to alveolar air pressure. Similar increases in Ptp and decreases in Pliq were obtained at higher lung volumes. Alveolar surface tension (T) was estimated from the Laplace equation for a spherical air-liquid interface, assuming that the radius of curvature varies as (volume)n, for -1/3 less than n less than 1/3. For uniform expansion of alveoli (n = 1/3), estimated T was 6 and 18 dyn/cm at 55 and 85% TLC, respectively, before treatment and increased to 23 and 40 dyn/cm following either Triton washing or ventilation. If pericapillary interstitial fluid pressure (Pi) equaled Pliq in edematous lungs, increases in T might reduce Pi and increase extravascular fluid accumulation in lungs made stiff by either Triton washing or cooling and ventilation using large tidal volumes.     

Monitoring changes in lung air and liquid volumes with electrical impedance tomography

Adler, A., R. Amyot, R. Guardo, J. H. T. Bates, and Y. Berthiaume. Monitoring changes in lung air and liquid volumes withelectrical impedance tomography. J. Appl.Physiol. 83(5): 1762-1767, 1997.Electricalimpedance tomography (EIT) uses electrical measurements at electrodesplaced around the thorax to image changes in the conductivitydistribution within the thorax. This technique is well suited tostudying pulmonary function because the movement of air, blood, andextravascular fluid induces significant conductivity changes within thethorax. We conducted three experimental protocols in a total of 19 dogsto assess the accuracy with which EIT can quantify changes in thevolumes of both gas and fluid in the lungs. In the first protocol, lungvolume increments from 50 to 1,000 ml were applied with a largesyringe. EIT measured these volume changes with an average error of 27 ± 6 ml. In the second protocol, EIT measurements were made at endexpiration and end inspiration during regular ventilation with tidalvolume ranging from 100 to 1,000 ml. The average error in the EITestimates of tidal volume was 90 ± 43 ml. In the third protocol,lung liquid volume was measured by instilling 5% albumin solution intoa lung lobe in increments ranging from 10 to 100 ml. EIT measured thesevolume changes with an average error of 10 ± 10 ml and was alsoable to detect into which lobe the fluid had been instilled. These results indicate that EIT can noninvasively measure changes in thevolumes of both gas and fluid in the lungs with clinically usefulaccuracy.

     

Chest wall motion during spontaneous breathing and mechanical ventilation in dogs

We measured the volume change of the thoracic cavity (delta Vth) and the volumes displaced by the diaphragm (delta Vdi) and rib cage (delta Vrc) in six pentobarbital-anesthetized dogs lying supine. A high-speed X-ray scanner (dynamic spatial reconstructor) provided three-dimensional images of the thorax during spontaneous breathing and during mechanical ventilation with paralysis. Tidal volume (VT) was measured by integrating gas flow. Changes in thoracic liquid volume (delta Vliq, presumably caused by changes in thoracic blood volume) were calculated as delta Vth - VT. Absolute volume displaced by the rib cage was not significantly different during the two modes of ventilation. During spontaneous breathing, thoracic blood volume increased during inspiration; delta Vliq was 12.3 +/- 4.1% of delta Vth. During mechanical ventilation, delta Vliq was nearly zero. Configuration of the relaxed chest wall was similar during muscular relaxation induced by either pharmacological paralysis or hyperventilation. Expiratory muscle activity produced 50 +/- 11% of the delta Vth during spontaneous breathing. We conclude that at constant VT the volume displaced by the rib cage is remarkably similar during the transition from spontaneous breathing to mechanical ventilation, while both diaphragmatic volume displacement and changes in intrathoracic blood volume decrease by a similar amount.     

Ventilation and perfusion distribution during altered PEEP in the left lung in the left lateral decubitus posture with unchanged tidal volume in dogs

Previous studies in anesthetized humans positioned in the left lateral decubitus (LLD) posture have shown that unilateral positive end-expiratory pressure (PEEP) to the dependent lung produce a more even ventilation distribution and improves gas exchange. Unilateral PEEP to the dependent lung may offer special advantages during LLD surgery by reducing the alveolar-to-arterial oxygen pressure difference {(A-a)PO2 or venous admixture} in patients with thoracic trauma or unilateral lung injury. We measured the effects of unilateral PEEP on regional distribution of blood flow (Q) and ventilation (V(A)) using fluorescent microspheres in pentobarbital anesthetized and air ventilation dogs in left lateral decubitus posture with synchronous lung inflation. Tidal volume to left and right lung is maintained constant to permit the effect on gas exchange to be examined. The addition of unilateral PEEP to the left lung increased its FRC with no change in left-right blood flow distribution or venous admixture. The overall lung V(A)/Q distribution remained relatively constant with increasing unilateral PEEP. Bilateral PEEP disproportionately increased FRC in the right lung but again produced no significant changes in venous admixture or V(A)/Q distribution. We conclude that the reduced dependent lung blood flow observed without PEEP occurs secondary to a reduction in lung volume. When tidal volume is maintained, unilateral PEEP increases dependent lung volume with little effect of perfusion distribution maintaining gas exchange.     

A computerized respiratory system including test functions of lung and circulation

The design of a microcomputer-controlled ventilator for automatic performance of lung function and circulatory tests has been described. It incorporates the characteristics of normal mechanical ventilation and also allows one to perform a multitude of test procedures for lung function and circulatory studies in paralyzed animals. The major components of the setup are a pump assembly with solenoid valves to direct gas flow, an electromechanical servo system, and a MS-DOS microcomputer system. The pump assembly has been constructed as a relatively simple device. Great versatility is created by the use of a microcomputer for the control of the ventilator. The software can be easily adapted to several other types of experimental studies. Besides the keyboard input the ventilator can be controlled by a remote computer system. This allows one to run an experimental protocol automatically and to use it in closed-loop servo ventilation. The flexibility in the choice of the respiratory parameters makes the ventilator suitable for lung function and circulatory studies during artificial ventilation. The ventilator has been successfully used in different animal studies during the last 6 yr.     

Bench and mathematical modeling of the effects of breathing a helium/oxygen mixture on expiratory time constants in the presence of heterogeneous airway obstructions

ABSTRACT: BACKGROUND: Expiratory time constants are used to quantify emptying of the lung as a whole, and emptying of individual lung compartments. Breathing low-density helium/oxygen mixtures may modify regional time constants so as to redistribute ventilation, potentially reducing gas trapping and hyperinflation for patients with obstructive lung disease. In the present work, bench and mathematical models of the lung were used to study the influence of heterogeneous patterns of obstruction on compartmental and whole-lung time constants. METHODS: A two-compartment mechanical test lung was used with the resistance in one compartment held constant, and a series of increasing resistances placed in the opposite compartment. Measurements were made over a range of lung compliances during ventilation with air or with a 8/22% mixture of helium/oxygen. The resistance imposed by the breathing circuit was assessed for both gases. Experimental results were compared with predictions of a mathematical model applied to the test lung and breathing circuit. In addition, compartmental and whole-lung time constants were compared with those reported by the ventilator. RESULTS: Time constants were greater for larger minute ventilation, and were reduced by substituting helium/oxygen in place of air. Notably, where time constants were long due to high lung compliance (i.e. low elasticity), helium/oxygen improved expiratory flow even for a low level of resistance representative of healthy, adult airways. In such circumstances, the resistance imposed by the external breathing circuit was significant. Mathematical predictions were in agreement with experimental results. Time constants reported by the ventilator were wellcorrelated with those determined for the whole-lung and for the low-resistance compartment, but poorly correlated with time constants determined for the high-resistance compartment. CONCLUSIONS: It was concluded that breathing a low-density gas mixture, such as helium/oxygen, can improve expiratory flow from an obstructed lung compartment, but that such improvements will not necessarily affect time constants measured by the ventilator. Further research is required to determine if alternative measurements made at the ventilator level are predictive of regional changes in ventilation. It is anticipated that such efforts will be aided by continued development of mathematical models to include pertinent physiological and pathophysiological phenomena that are difficult to reproduce in mechanical test systems.     

Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide.

Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control, PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction.