Effects of end-expiratory lung volume on lung mechanics in normal and edematous lungs

This study determined the effects of end-expiratory pressures (EEP) and alterations in end-expiratory lung volume (EELV) on lung compliance (CL) and pulmonary resistance to gas flow (RP) in 20 cats with normal and edematous lungs. EELV was varied using EEP ranging from -8 to +10 cm H2O. Negative EEP was used to decrease EELV of the healthy lung causing CL to decrease and RP to increase. Positive EEP in the healthy lung also caused CL to decrease but did not significantly affect RP. After inducing pulmonary edema using alloxan, functional residual capacity (FRC) decreased 38%, CL decreased 66% and RP increased 106% (p less than 0.001). An EEP of 4 cm H2O returned EELV to normal FRC levels and produced maximum values for CL. Increases in EEP to 4 cm H2O also caused decreases in RP in the edematous lungs but further increase did not cause significant changes in RP. These results show that (1) relatively low levels of EEP returned EELV to normal FRC levels in alloxan-induced pulmonary edema, and (2) optimal lung mechanics were obtained when EELV was equal to or slightly above normal FRC values in both healthy and edematous lungs.     

Mechanisms of pulmonary edema induced by tumor necrosis factor-alpha

We tested the hypothesis that human recombinant tumor necrosis factor-alpha (TNF) promotes pulmonary edema by neutrophil-dependent effects on the pulmonary vasculature. The isolated guinea pig lung was perfused with phosphate-buffered Ringer's solution with or without human neutrophils. The infusion of neutrophils (9 x 10(6) total) into lungs isolated after the in vivo administration of TNF (3.2 x 10(5) units/kg) resulted in weight gain (+1.951 +/- 0.311 g versus -0.053 +/- 0.053 g in control) and an increase in the lung (wet-dry)-to-dry weight ratio (8.3 +/- 0.5 versus 6.0 +/- 0.2 in control), indicating the formation of pulmonary edema. The neutrophil-dependent pulmonary edema induced by TNF was associated with a combination of increased capillary permeability (capillary filtration coefficient [Kf,c], 0.170 +/- 0.048 g/min/cm H2O/g at 30 minutes versus 0.118 +/- 0.008 g/min/cm H2O/g at baseline) and increased pulmonary capillary pressure (Ppc, 12.8 +/- 0.8 cm H2O at 60 minutes versus 6.0 +/- 0.3 cm H2O at baseline). The Ppc increase was mediated by thromboxane A2 (TXA2) because the TXA2 synthetase inhibitor Dazoxiben (0.5 mM) prevented the effect (Ppc, 6.7 +/- 0.6 cm H2O at 60 minutes with Dazoxiben), and thromboxane B2 (TXB2) levels were increased in the pulmonary venous effluent (5,244 +/- 599 pg/ml at 60 minutes versus 60 +/- 13 pg/ml at baseline). Studies using WEB-2086 (37 microM), a platelet activating factor (PAF) receptor antagonist, indicated that PAF mediated the increased vascular permeability (Kf,c, 0.107 +/- 0.014 g/min/cm H2O/g at 30 minutes using WEB-2086) and, in part, the increased Ppc (Ppc, 8.4 +/- 0.7 cm H2O at 60 minutes using WEB-2086). In addition, alterations of endothelial peripheral actin bands were noted after TNF administration. The data indicate that TNF induces neutrophil-dependent pulmonary edema associated with increased Ppc (mediated by TXA2 and PAF), increased Kf,c (mediated by PAF), and changes in endothelial peripheral actin bands.     

允许性高碳酸血症对急性肺损伤绵羊肺力学及血流动力？…

目的 探讨允许性高碳酸血症（ＰＨＣ）对急性肺损伤（ＡＬＩ）绵羊肺力学及血流动力学的影响。方法 观察不同潮气量（ＶＴ）时，１８只ＡＬＩ绵羊肺气体交换、肺力学和血流动力学的改变。结果 当ＶＴ从１６ｍｌ／ｋｇ降至４～７ｍｌ／ｋｇ时，绵羊均出现ＰＨＣ，动脉血氧分压、氧饱和度和混合静脉血氧饱和度显降低（Ｐ〈０．０５）。ＰＨＣ时气道压力显降低（Ｐ〈０．０５），气道阻力明显增高；体循环和肺循环阻力指数、左心     

Effect of edema on segmental vascular resistance in isolated lamb lungs determined by micropuncture

We have studied the mechanical effects of fluid accumulation on the pulmonary vasculature in 28 isolated blood perfused lungs of newborn lambs. Vascular resistance in the pulmonary arteries, microvessels, and veins was determined by micropuncture measurement of microvascular pressures, and regional distribution of blood flow in the lungs was determined using radiolabelled microspheres both before and after the development of varying degrees of hydrostatic edema. Edema was induced by raising venous pressure. During measurements, alveolar and venous pressures were kept constant at 7 and 8 cm H2O, respectively, as well as lung blood flow (540 +/- 107 ml/min). All vascular pressures were referenced to the superior surface of the lung, site of all micropunctures. Active vasomotor changes were eliminated by addition of papaverine to the perfusate. Under baseline nonedematous conditions in the absence of vasomotor tone, 17% of the total pressure drop was in arteries, 41% was in microvessels, and 42% was in veins. With the development of alveolar edema (80 +/- 13% weight gain), there was no change in total or segmental vascular resistance, but after 148 +/- 97% weight gain, total pulmonary vascular resistance increased by 74%. Segmental pressure drop increased in arteries by 172% and in microvessels by 132% but decreased by 22% in the venous segment. Regional distribution of blood flow remained unchanged. Possible mechanisms for increased resistance to blood flow may be compression of small arterioles and venules (less than 20 micron diameter) by liquid cuffs and/or occlusion of microvessels by the weight of alveolar liquid.     

Pulmonary vascular tone improves pulmonary gas exchange in the adult respiratory distress syndrome

Hemodynamics, blood gases, lung mechanics, and the distributions of ventilation-perfusion ratios (VA/Q) were studied before and after iv diltiazem, 0.5 mg/kg over 30 min, in 6 patients with pulmonary hypertension secondary to the adult respiratory distress syndrome (ARDS) ventilated with 7 to 20 cm H2O positive end-expiratory pressure (PEEP). Diltiazem decreased systemic and pulmonary arterial pressures without changes in cardiac output and in filling pressures of the heart, and with a slowing of heart rate. Pulmonary vascular resistances decreased from 401 +/- 59 to 329 +/- 58 dyne.s.cm-5.m2 (mean +/- SEM), p less than 0.01. Arterial Po2 decreased from 87 +/- 10 to 80 +/- 11 mm Hg (p less than 0.02) without changes in arterial PCO2, mixed venous PO2, and O2 consumption. Lung compliance and airway resistances did not change. Diltiazem increased true shunt from 23 +/- 5 to 30 +/- 7% of total blood flow (p less than 0.02) without other modification in the pattern of VA/Q distribution as measured by the multiple inert gas elimination technique. These results suggest that pulmonary vascular tone contributes to the maintenance of VA/Q matching in patients with ARDS.     

Perfluorochemical artificial blood as a volume expander in hypoxemic respiratory failure in dogs

The perfluorochemical O2-transport fluid, Fluosol-DA 20 percent (PFC), is being clinically evaluated as a volume expander in patients who are unable to receive blood products. Since patients treated with Fluosol-DA may be at risk of developing adult respiratory distress syndrome (ARDS) as a complication of the original disorder for which they were transfused, we examined central hemodynamics and gas exchange in anesthetized O2-ventilated dogs with oleic-acid induced pulmonary edema before and after transfusion with 400 ml of either PFC (n = 5) or whole blood (n = 5). Transfusion produced similar increases in cardiac output, pulmonary and systemic vascular pressures and intrapulmonary shunt in the two groups. Arterial O2 tension, however, fell from 209 +/- 117 to 172 +/- 81 mmHg in the blood transfused group but increased from 219 +/- 145 to 302 +/- 138 mmHg in the PFC group. Arterial O2 content, on the other hand, increased in the blood transfused group due to an increase in hematocrit, but fell with PFC because of hemodilution. This lower total arterial O2 content in the PFC group was, however, compensated for by more efficient O2 transport by the PFC in that the PFC arteriovenous O2 content difference accounted for 26 percent of the total arteriovenous O2 content difference, making it about four times as efficient as hemoglobin in tissue O2 delivery. Fluosol DA, 20 percent, is an effective volume expander in this model of hypoxemic respiratory failure, and it can transport significant amounts of O2 even in the presence of a substantial intrapulmonary shunt.     

Pulmonary and systemic effects of increased negative inspiratory intrathoracic pressure in dogs

Croup and epiglottitis, which cause greater than normal negative inspiratory intrathoracic pressure (NIIP), have been associated with pulmonary edema. To examine the effects of increased NIIP per se on blood gases, hemodynamics, and lung water content, we carried out 2 types of experiments in 18 anesthetized dogs. Short-term, low-pressure experiments (6 control dogs and 6 dogs that generated intratracheal pressures of -12 cm H2O during inspiration for 3 h) and long-term, high-pressure experiments (6 dogs that generated -20 cm H2O during inspiration for 6 h). In the short-term, low-pressure experiments, animals made to generate negative inspiratory pressure differed from control dogs by demonstrating decreased pleural pressure (p less than 0.01), increased arterial PCO2 (p less than 0.05), and decreased minute volume (p less than 0.05); no differences occurred in hemodynamic data (pulmonary arterial, left atrial, and aortic pressures and cardiac index) and in extravascular lung water (indicator dilution and gravimetric analyses). Similarly, in the long-term, high-pressure dogs, arterial PCO2 increased (p less than 0.05) and lung water was normal by gravimetric analysis. We conclude that both 3 and 6 h of increased NIIP cause CO2 retention but have minimal effects on hemodynamics and lung fluid exchange.     

Factors affecting bronchial blood flow through bronchopulmonary anastomoses in dogs

Most of the bronchial arterial blood flow (Qbr) drains through bronchopulmonary anastomoses into the pulmonary circulation, and the remainder goes into the systemic venous system via the bronchial veins. We studied the relationship between blood flow through bronchopulmonary anastomoses, and alveolar pressure and pulmonary vascular pressures as well as hydrostatic pressure in the bronchial veins in 10 adult dogs. The pulmonary artery and vein of the experimental left lower lobes (LLL) of open-chested, anesthetized dogs were isolated and connected to reservoirs. That part of the Qbr that flowed through bronchopulmonary anastomoses into the reservoirs was continuously measured at constant pulmonary vascular pressures of 0 cm H2O relative to the lung base. Any bronchial blood volume that retained within the LLL was estimated from changes in lobe weight. The lobe was distended with 5% CO2 and air, at alveolar pressures of 5, 10, or 20 cm H2O in a random sequence. Because bronchial veins drain into the azygos vein, the bronchial venous pressure was elevated by snaring the azygos vein. The mean anastomotic Qbr was 4.4 +/- 1.1 (mean +/- SEM) ml/min and it decreased by 23 and 39% when alveolar pressure was raised from 5 cm H2O to 10 and 20 cm H2O respectively (p less than 0.05). Approximately 75% of the total anastomotic Qbr was collected from the pulmonary venous reservoir at all alveolar pressures. When both pulmonary artery and venous pressures were increased higher than the alveolar pressure (zone III), azygos snaring increased the anastomotic Qbr by 13 and 31% at alveolar pressures of 10 and 20 cm H2O, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of external continuous negative pressure ventilation compared with those of continuous positive pressure ventilation in dogs with acute lung injury

Patients with noncardiogenic pulmonary edema requiring ventilatory assistance are usually supported with CPPV using positive end-expiratory pressure (PEEP), but CPPV requires endotracheal intubation and may decrease cardiac output (QT). The purpose of this study was to examine thoracoabdominal continuous negative pressure ventilation (CNPV) using external negative end-expiratory pressure (NEEP). The effects on gas exchange and hemodynamics were compared with those of CPPV with PEEP, with the premise that CNPV might sustain venous return and improve QT. In 6 supine, anesthetized and paralyzed dogs with oleic-acid-induced pulmonary edema, 30 min of CNPV was alternated twice with 30 min of CPPV. Positive and negative pressure ventilation were carefully matched for fractional inspired oxygen concentration (FIO2 = 0.56), breathing frequency, and tidal volume. In addition, we matched the increase in delta FRC obtained with the constant distending pressures produced by both modes of ventilation. An average of -9 cm H2O of NEEP produced the same delta FRC as 10.8 cm H2O of PEEP. Gas exchange did not differ significantly between the 2 modes. However, QT was 15.8% higher during CNPV than during CPPV (p less than 0.02). Mixed venous oxygen saturation also improved during CNPV compared with that during CPPV (58.3 versus 54.5%, p less than 0.01). Negative pressure ventilation using NEEP may be a viable alternative to positive pressure ventilation with PEEP in the management of critically ill patients with noncardiogenic pulmonary edema. It offers comparable improvement in gas exchange with the advantages of less cardiac depression and the possible avoidance of endotracheal intubation.     

The Effects of Endoscopic Sclerotherapy Combined with Transhepatic Variceal Obliteration on Portal Hemodynamics

We studied the effects of endoscopic sclerotherapy with transhepatic variceal obliteration on portal hemodynamics in 20 patients with cirrhosis (six with a spontaneous splenorenal shunt and 14 without it). Portal venous flow 1 month after combined therapy (measured by pulsed Doppler flowmeter) was significantly increased compared with that before therapy (n = 20, 843 +/- 339 vs. 669 +/- 253 ml/min, p less than 0.001). Portal vein catheterization and portal venous flow measurement were repeated 18 months after therapy in eight patients without a splenorenal shunt before therapy and in two patients with a splenorenal shunt before therapy. Two of the former developed a splenorenal shunt. In these 10 patients, portal venous flow before, one month, and 18 months after therapy was 617 +/- 219, 784 +/- 227, and 720 +/- 224 ml/min, respectively, and in 8 of 10 patients the portal venous flow at 18 months remained similar to the values at one month. Portal vein pressures were not significantly elevated 18 months after therapy (35.4 +/- 6.4 vs. 33.6 +/- 5.1 cm H2O) and the mean portal vein pressure change was 2.75 cm H2O (range -6 to +7.5 cm H2O). To summarize, portal venous flow was significantly increased one month after combined sclerotherapy in cirrhotics, the portal venous flow at 18 months remained similar to the values at 1 month in most patients, and the change in portal vein pressure after therapy was small.     

Relationship of ultrafiltration and anastomotic flow in isolated rat lungs.

OBJECTIVE: When arterial and venous pressures are increased to equal values in "stop-flow" studies, perfusate continues to enter the pulmonary vasculature from the arterial and venous reservoirs. Losses of fluid from the pulmonary vasculature are due to ultrafiltration and flow through disrupted anastomotic (bronchial) vessels. This study compared the relative sites of ultrafiltration and anastomotic flows at low and high intravascular pressures. METHODS: Isolated rat lungs were perfused for 10 minutes with FITC-dextran, which was used to detect ultrafiltration. Arterial and venous catheters were then connected to reservoirs containing radioactively labeled dextrans at 20 or 30 cm H2O for 10 minutes. The vasculature was subsequently flushed into serial vials, and ultrafiltration and vascular filling during the equal-pressure interval were calculated. RESULTS: Ultrafiltration equaled 0.43 +/- 0.11 mL at 20 cm H2O and was similar to the volume of fresh arterial and venous perfusate which entered and remained in the pulmonary vasculature during the equal-pressure interval (0.45 +/- 0.10 mL). At 30 cm H2O, 0.80 +/- 0.23 mL entered and remained in the vasculature during the equal-pressure interval, replacing the original perfusate, and calculated transudation (0.56 +/- 0.09 mL) was not significantly more than at 20 cm H2O. Fluid also entered the airspaces at 30 cm H2O but not at 20 cm H2O. CONCLUSIONS: At 20 cm H2O, flow through anastomotic vessels occurs at sites that are at the arterial and venous ends of the microcirculation. Flow in exchange vessels remains minimal, permitting measurements of ultrafiltration and exchange. Losses of perfusate from the pulmonary vessels complicate measurements of ultrafiltration at 30 cm H2O.     

Effect of edema on segmental vascular resistance in isolated perfused rat lungs

We have determined the effect of hydrostatic edema on total and segmental vascular resistances in the rat lung. Lungs of 12 adult rats, body weight 515 +/- 42 g, were isolated and perfused with blood. To investigate the role of vasoactivity on edema effects, we studied two groups of lungs; group I (n = 6) were untreated and group II (n = 6) were treated with papaverine hydrochloride to paralyze the vasculature. Initially blood flow was adjusted to keep pulmonary artery pressure approximately 15 cmH2O, left atrial and airway pressures being 8 and 7 cmH2O, respectively, and then kept unchanged thereafter (18 +/- 3 ml/kg/min). Hydrostatic edema was induced by raising venous pressure and pulmonary artery pressure measured continuously. In 4 lungs from each group, during baseline and after the development of severe edema, we partitioned the pulmonary circulation into arteries, microvessels, and veins by measuring pressures in 20-50 microns diameter subpleural arterioles and venules with the micropipette-Servonull method. Baseline total vascular resistance was similar in the two groups. Interstitial and early alveolar edema did not affect pulmonary vascular pressures. With severe edema (W/D ratio: 17 +/- 2), pressures in pulmonary artery and arterioles increased significantly in both groups; venular pressures did not change. Total resistance increased by 250% in group I and by 224% in group II lungs. Arterial resistance increased 3-5-fold in both groups, as did microvascular resistance. Venous resistances also increased in both groups, although to a lesser extent. The increase in total and segmental vascular resistances was not significantly different in the two groups of lungs. We conclude that in isolated rat lungs only severe edema results in an increase in total vascular resistance, mainly due to an increase in arterial and microvascular resistances, with a smaller increase in venous resistance. This appears to be a mechanical effect of edema on the vasculature and not a result of active vasomotion.     

Prostaglandin E1 in the adult respiratory distress syndrome. Benefit for pulmonary hypertension and cost for pulmonary gas exchange

Prostaglandin E1 (PGE1) has been reported to improve survival in patients with the adult respiratory distress syndrome (ARDS). However, the effects of this pulmonary vasodilating compound on gas exchange have been little documented. We therefore measured hemodynamics, blood gases, and the distributions of ventilation-perfusion ratios (VA/Q), using the multiple inert gas elimination technique, at baseline and during infusion of PGE1 0.02 to 0.04 microgram.kg-1.min-1 in six patients with pulmonary hypertension secondary to ARDS ventilated with 10 cm H2O positive end-expiratory pressure. PGE1 decreased systemic arterial mean pressure (-16%) and pulmonary arterial mean pressure (-15%) and increased cardiac index (+20%) and heart rate (+11%). Arterial PO2 decreased from 99 +/- 6 to 77 +/- 8 mm Hg (p less than 0.01, mean +/- SEM) with no change in mixed venous PO2 and in O2 consumption. PGE1 increased true shunt from 21 +/- 4 to 32 +/- 5% of total blood flow (p less than 0.01) with no significant modification in the pattern of VA/Q distribution. Thus, in ARDS, pulmonary hypertension is reduced by PGE1 at the price of a deterioration in pulmonary gas exchange. The clinical relevance of these findings remains to be evaluated.     

Comparison of conventional and high-frequency ventilation in piglets after lung lavage

A piglet model of respiratory failure was used to compare airway pressures required for adequate gas exchange by a conventional positive pressure ventilator (CMV) and a high-frequency pneumatic flow interrupter (HFFI). Twelve newborn piglets (age means = 3.8 days and weight means = 1.4 kg) were given saline lung lavages after receiving intravenous Ketamine and Pavulon. Femoral and jugular vessels were catheterized for measurements of aortic and pulmonary blood pressures and gases, cardiac output, hematocrit, glucose and for the infusion of fluids. Airway pressures were measured 5 mm above the distal tip of the endothracheal tube. Lung lavage resulted in decreased static compliance and a twofold increase in pulmonary shunting. Following lavage the animals were kept on 100% oxygen and randomly assigned to either CMV (30/min) or HFFI (600/min) ventilation and thereafter were switched every 30 minutes to the alternate mode. Inspiratory duration was 33% of the total respiratory cycle during CMV and 30-50% for HFFI. Sixteen pairs of data comparing both ventilator modes were used. Blood gases, cardiovascular variables, alveolar-arterial oxygen gradient, and pulmonary shunting were not different with either ventilator. Positive end-expiratory pressure (5.3 and 5.6 cm H2O) and mean airway pressure (12.5 and 11.9 cm H2O) were equal for CMV and HFFI, respectively. Peak inspiratory pressure was significantly lower for HFFI (23.1 +/- 3.7 SD cm H2O) than for CMV (30.4 +/- 5.5 SD cm H2O). The lower peak inflation pressure required during HFFI ventilation may reduce the potential for lung rupture.     

Effect of a sustained inflation on regional distribution of gas and perfluorocarbon during partial liquid ventilation

OBJECTIVE: To study the effect of a sustained inflation (SI) maneuver on the regional distribution of gas and perfluorocarbon (PFC) during partial liquid ventilation (PLV) in normal pigs using computerized densitometry. STUDY DESIGN: Observational study. SETTING: Animal research laboratory. PARTICIPANTS: Three healthy anaesthetized pigs. INTERVENTIONS: Partial liquid ventilation, lung recruitment, CT densitometry. METHODOLOGY: Lungs were filled with PFC to "liquid functional residual capacity (FRC)" (35-41 ml/kg) and CT images were recorded at a series of predetermined airway pressure levels (0, 20, 30, 40 cm H2O) both before and after SI to an airway pressure of 40 cm H2O for 30 sec. Anterior, middle, and posterior regions from upper (apical lung) to lower (basal lung) CT slices were analyzed at each pressure level for Hounsfield units to describe the relative distribution of gas and PFC before and after SI. Using an occlusion technique true gas volume above FRC was determined at each pressure level, before and after SI, and a pressure-volume (gas) envelope determined for each animal. RESULTS: At low airway pressures (<20 cm H2O) gas was distributed predominantly to the anterior (non-dependent) part of the lung and PFC predominantly to the posterior (dependent) lung. Gas and liquid were more uniformly distributed throughout the lung at airway pressures >20 cm H2O. Generation of a pressure-volume (gas) envelope for each animal demonstrated an increase in total gas volume above FRC at each pressure level following recruitment of the lung with SI. However, marked regional differences were evident with the greatest effects of SI seen at higher airway pressures in posterior and basal regions. CONCLUSION: The healthy PFC filled lung demonstrates an increase in total gas volume following SI. CT densitometry suggests marked heterogeneity of gas/PFC distribution between different regions of lung and heterogeneity of response to SI.     

持续气道正压通气对急性心源性肺水肿犬呼吸及循环功能的影响

目的研究持续气道正压(CPAP)通气对急性心源性肺水肿(ACPE)犬呼吸及循环功能的影响。方法分别监测10条犬健康状态及ACPE发生后自主呼吸、5cmH2O(1cmH2O=0.098kPa)、10cmH2O、15cmH2OCPAP时的胸腔负压(Pt)、中心静脉压(CVP)、心输出量(CO)、平均动脉压(BPm)、肺动脉楔压(PAWP)。结果与健康状态相比,ACPE犬呼吸增强、增快,Pt由-(4.90±0.09)cmH2O上升至-(10.90±0.75)cmH2O,CVP由(10.1±0.4)mmHg下降至(8.0±0.7)mmHg,CO由(1.52±0.13)L/min下降至(0.85±0.09)L/min,PAWP升高(P均<0.05)。CVP与Pt变化呈正相关(r=0.78,P<0.01)。5及10cmH2OCPAP时Pt值恢复至-(6.53±0.11)cmH2O和-(5.14±0.25)cmH2O,呼吸形式基本恢复正常,CVP升至(11.6±0.7)mmHg和(14.2±0.2)mmHg,CO增加至(1.45±0.11)L/min和(1.24±0.11)L/min,其中5cmH2OCPAP组PAWP下降(P均<0.05)。15cmH2OCPAP时,呼吸浅快,Pt为-(0.82±0.37)cmH2O,CO为(0.82±0.07)L/min,其他血流动力学指标皆恶化(P均<0.05)。结论犬ACPE发生时,呼吸运动显著增强,Pt升高,并导致CVP和CO的下降;适当CPAP通过改善呼吸功能,调节Pt改善ACPE犬的心功能。     

Application of tracheal gas insufflation to acute unilateral lung injury in an experimental model

In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the injured lung without causing overdistension of the normal lung. In eight anesthetized dogs, left lung saline lavage was performed until Pa(O(2))/FI(O(2)) fell below 100 mm Hg. Then, the dogs were reintubated with a Univent single lumen endotracheal tube that incorporates an internal catheter to provide TGI. After injury, increasing PEEP from 3 to 10 cm H(2)O did not change gas exchange, hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory lung volume (EELV) constant, improved Pa(O(2))/FI(O(2)) from 212 +/- 43 to 301 +/- 38 mm Hg (p < 0.01) while Pa(CO(2)) and airway pressures decreased (p < 0.01). During selective TGI, reducing tidal volume to 5.2 ml/kg while keeping EELV constant, normalized Pa(CO(2)), did not affect Pa(O(2))/FI(O(2)), and decreased end-inspiratory plateau pressure from 16.6 +/- 1.0 to 11.9 +/- 0.5 cm H(2)O (p < 0.01). In unilateral lung injury, we conclude that selective TGI (1) improves oxygenation at a lower pressure cost as compared with conventional mechanical ventilation, (2) allows reduction in tidal volume without a change in alveolar ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung injury.     

Normalization of arterial blood gases after treatment of surfactant-deficient lambs with Tween 20

Pulmonary surfactant (PS) is capable of lowering surface tension at an air-water interface to less than 10 dynes/cm. This property of PS is believed to be important for normal lung function. We tested the detergent Tween 20, which cannot lower surface tension at an air-water interface to less than 25 dynes/cm, for its ability to promote reasonable gas exchange in surfactant-deficient lambs delivered prematurely at 120 to 124 days gestation. Lambs were treated at birth with 75 mM NaCl (control), 5% Tween 20 in 75 mM NaCl, or PS in 75 mM NaCl and placed on infant ventilators. Control lambs had poor oxygenation and were in respiratory failure at 30 min of age (arterial PCO2 of 75.8 +/- 11 mmHg (mean +/- SE)) despite peak inspiratory pressures (PIP) of 32 +/- 0.7 cm H2O. Pulmonary surfactant treatment allowed adequate ventilation with a PIP of 23.8 +/- 1.2 cm H2O. Tween treatment also allowed adequate ventilation with a PIP of only 27 +/- 1.3 cm H2O. Minimal surface tensions in alveolar washes of control and Tween-treated lambs were 28.7 +/- 1.3 and 26.7 +/- 2.3 dynes/cm, respectively, compared with less than 10 dynes/cm for PS-treated lambs. Thus, Tween 20 did not alter the alveolar wash minimal surface tension when compared with that of the control animals but it did significantly improve gas exchange and lung compliance.     

Effects of lung volume and positive airway pressure on collateral resistance

Nine mongrel dogs were anesthetized, paralysed, ventilated, and placed in an iron lung. Each animal was transiently connected to a spirometer and the respiratory system compliance measured by applying negative or positive extrathoracic pressures (from -20 cm H2O to +20 cm H2O in 5 cm H2O steps). A sub-lobar bronchus was wedged with a 5.5 mm bronchoscope, and a 5f Swan-Ganz catheter was inserted into the lumen of the bronchoscope; one port served to introduce a 200 ml.min-1 flow of 5% CO2 in air, the other to measure the pressure in the wedged segment. Rcoll was measured with extrathoracic pressures in the iron lung ranging from 0 to -20 cm H2O (NEP) and 0 to +20 cm H2O (PEP) in 5 cm H2O steps, and under expiratory positive airway pressure (EPAP) of 5, 10, 15, and 20 cm H2O. The maximal changes in FRC were an increase of 1009 +/- 49 ml (mean +/- SEM) with NEP and a decrease of 397 +/- 33 ml with PEP. Increasing FRC decreased Rcoll while decreasing FRC markedly increased it. EPAP induced similar decreases in Rcoll as NEP of equal pressure. This effect of EPAP was inhibited by simultaneously applying PEP of equal pressure. We conclude that resistance to collateral flow is highly dependent on lung volume, and that positive airway pressure decreases Rcoll by its effects on lung volume.     

Effect of pentoxifylline on hemodynamics, alveolar fluid reabsorption, and pulmonary edema in a model of acute lung injury

We investigated the effect of pentoxifylline (PTX) on the development of pulmonary edema in a model of adult respiratory distress syndrome in rabbits. Lung injury was induced by repeated saline lavages in adult rabbits weighing 2.5 to 3.5 kg. Rabbits pretreated with PTX (20 mg/kg bolus followed by 20 mg/kg/h infusion) developed significantly lower amounts of lung edema 4 h after saline lavage (extravascular lung water to dry weight ratio [W/D], 6.9 +/- 0.6 SD versus 8.9 +/- 0.5 in control animals). PTX produced a 25% increase in cardiac output, but there were no differences between treated and untreated groups in calculated pulmonary vascular resistance or microvascular pressure. To determine whether PTX could have lowered pulmonary venous resistance and thus lowered effective microvascular pressure for fluid filtration, we directly measured pulmonary artery and left atrial pressures, and measured by micropuncture the pressure in 20 to 40 microns subpleural venules in four open-chested rabbits 3 to 4 h after lavage. Venous resistance was low (venous pressure drop 0.9 +/- 0.1 mm Hg) and was unchanged by PTX infusion. To determine if PTX decreased lung water by accelerating active alveolar fluid reabsorption, a single 60-ml aliquot of saline was instilled into the lungs of normal rabbits treated with saline or PTX. Both groups had a similar decrease in lung water content 1 and 4 h later. Our data indicate that PTX reduces edema formation in rabbits after saline lavage, not by lowering microvascular pressures for fluid filtration or by acceleration alveolar fluid reabsorption, but possibly by its anti-inflammatory effect on neutrophil function.