Partial Liquid Ventilation Reduces Fluid Filtration of Isolated Rabbit Lungs with Acute Hydrochloric Acid-induced Edema

Background: Hydrochloric acid aspiration increases pulmonary microvascular permeability. The authors tested the hypothesis that partial liquid ventilation has a beneficial effect on filtration coefficients in acute acid-induced lung injury.

Methods: Isolated blood-perfused rabbit lungs were assigned randomly to one of four groups. Group 1 (n = 6) served as a control group without edema. In group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6), pulmonary edema was induced by intratracheal instillation of hydrochloric acid (0.1 N, 2 ml/kg body weight). Filtration coefficients were determined 30 min after this injury (by measuring loss of perfusate after increase of left atrial pressure). Group 2 lungs were gas ventilated, and group 3 lungs received partial liquid ventilation (15 ml perfluorocarbon/kg body weight). In group 4 lungs, the authors studied the immediate effects of bronchial perfluorocarbon instillation on ongoing filtration.

Results: Intratracheal instillation of hydrochloric acid markedly increased filtration coefficients when compared with noninjured control lungs (2.3 +/- 0.7 vs. 0.31 +/- 0.08 ml [middle dot] min-1 [middle dot] mmHg-1 [middle dot] 100 g-1 wet lung weight, P < 0.01). Partial liquid ventilation reduced filtration coefficients of the injured lungs (to 0.9 +/- 0.3 ml [middle dot] min-1 [middle dot] mmHg-1 [middle dot] 100 g-1 wet lung weight, P = 0.022). Neither pulmonary artery nor capillary pressures (determined by simultaneous occlusion of inflow and outflow of the pulmonary circulation) were changed by hydrochloric acid instillation or by partial liquid ventilation. During ongoing filtration, bronchial perfluorocarbon instillation (5 ml/kg body weight) immediately reduced the amount of filtered fluid by approximately 50% (P = 0.027).     

Changes in Pulmonary Blood Flow during Gaseous and Partial Liquid Ventilation in Experimental Acute Lung Injury

Background: It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury.

Methods: After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group.

Results: During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon.     

Changes in pulmonary blood flow during gaseous and partial liquid ventilation in experimental acute lung injury

BACKGROUND: It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury. METHODS: After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group. RESULTS: During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon. CONCLUSIONS: In the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.     

Partial liquid ventilation in acute salt water-induced lung injury

BACKGROUND AND OBJECTIVES: Salt-water aspiration results in pulmonary oedema and hypoxia. We tested the hypothesis that partial liquid ventilation has beneficial effects on gas exchange and rate of survival in acute and extended salt water-induced lung injury. METHODS: Anaesthetized, ventilated rats (tidal volume 6 mL kg(-1), PEEP 5 cmH2O) received a tracheal salt-water instillation (3%, 8 mL kg(-1) body weight) and were randomly assigned to three groups (n = 10 per group). While lungs of Group 1 were gas-ventilated, lungs of Group 2 received a single perfluorocarbon instillation (30 min after the injury, 5 mL kg(-1) perfluorocarbon) and lungs of Group 3 received an additional continuous perfluorocarbon application into the treachea (5 mL kg(-1) h(-1)) Arterial blood gases were measured with an intravascular blood gas sensor. RESULTS: Salt-water instillation resulted in a marked decrease in PaO2 values within 30 min (from 432 +/- 65 to 83 +/- 40 mmHg, FiO2 = 1.0, P < 0.01). Arterial oxygenation improved in all three groups irrespective of treatment. We observed no significant differences between groups in peak PaO2 and PaCO2 values. CONCLUSIONS: Our results suggest that partial liquid ventilation has no additional beneficial effects on gas exchange after life-threatening salt water-induced lung injury when compared to conventional gas ventilation with positive end-expiratory pressure.     

Partial liquid ventilation: effects of closed breathing systems, heat-and-moisture-exchangers and sodalime absorbers on perfluorocarbon evaporation

BACKGROUND AND OBJECTIVES: During partial liquid ventilation perfluorocarbons are instilled into the airways from where they subsequently evaporate via the bronchial system. This process is influenced by multiple factors, such as the vapour pressure of the perfluorocarbons, the instilled volume, intrapulmonary perfluorocarbon distribution, postural positioning and ventilatory settings. In our study we compared the effects of open and closed breathing systems, a heat-and-moisture-exchanger and a sodalime absorber on perfluorocarbon evaporation during partial liquid ventilation. METHODS: Isolated rat lungs were suspended from a force transducer. After intratracheal perfluorocarbon instillation (10 mL kg(-1)) the lungs were either ventilated with an open breathing system (n = 6), a closed breathing system (n = 6), an open breathing system with an integrated heat-and-moisture-exchanger (n = 6), an open breathing system with an integrated sodalime absorber (n = 6), or a closed breathing system with an integrated heat-and-moisture-exchanger and a sodalime absorber (n = 6). Evaporative perfluorocarbon elimination was determined gravimetrically. RESULTS: When compared to the elimination half-life in an open breathing system (1.2 +/- 0.07 h), elimination half-life was longer with a closed system (6.4 +/- 0.9 h, P 0.05) when compared to a closed system. CONCLUSIONS: Evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers.     

Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns

Pulmonary failure remains the major determinant of mortality and morbidity following burn injury. We hypothesized that intratracheal instillation of perfluorocarbon liquids could be a therapeutic measure in combination with conventional mechanical ventilation to improve pulmonary gas exchange in acute respiratory distress syndrome with thermal injury. Forty-five New Zealand rabbits were used for this prospective and randomized experimental study. The animals were burned by scald to reach full-thickness 40% burn surface area. After inducing respiratory distress by repeated lung lavage with saline, animals were divided randomly into three groups of 15 rabbits each. First group (control group) received conventional treatment (continuous positive-pressure ventilation) using a FiO(2) of 1.0, tidal volume of 12 ml/kg, respiratory frequency of 30 cycles/min and PEEP of 6 cm H(2)O. Second group was treated with 9 ml/kg of intratracheal perfluorocarbon. Third group was treated with 15 ml/kg of intratracheal perfluorocarbon. All groups were ventilated for 6 h. In the perfluorocarbon groups, PaO(2) increased significantly (P<0.05) from 46+/-4 to 439+/-10 mmHg compared to the control group in a dose-related manner. In pulmonary parameters we observed significant (P<0.05) decrease in mean airway pressures from the pre-treatment value of 11.44+/-0.15 cm H(2)O to the post treatment 10.22+/-0.12 cm H(2)O and increase (P<0.05) in respiratory system compliance from 1.8+/-0.02 to 2.46+/-0.07 ml/cm H(2)O with the perfluorocarbon. Perfluorocarbon instillation did not result in statistically significant changes in arterial pressure, heart rate and central venous pressure. In conclusion, partial liquid ventilation with perfluorocarbon is a new technique leading to a marked and sustained improvement in oxygenation and pulmonary function in an experimental model of ARDS in burns.     

Combining partial liquid ventilation and prone position in experimental acute lung injury.

BACKGROUND: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS: ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS: The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.     

Combining Partial Liquid Ventilation and Prone Position in Experimental Acute Lung Injury

Background: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI.

Methods: ALI was induced in 20 medium-sized pigs (29.2 +/- 2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position.

Results: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone.     

Treatment of Pulmonary Hypertension and Hypoxia Due to Oleic Acid Induced Lung Injury with Intratracheal Prostaglandin E1 during Partial Liquid Ventilation

Background: Partial liquid ventilation using perfluorocarbon liquids may be of therapeutic benefit in patients with acute respiratory failure. This study investigated the effects of prostaglandin E1 (PGE1) delivered intratracheally during partial liquid ventilation on lung function and pulmonary circulation in rabbits with acute respiratory distress syndrome.

Methods: Lung injury was induced by intravenous oleic acid in adult Japanese white rabbits, 1 h after which they were divided into four groups of 10 animals. Group 1 received mechanical ventilation alone, group 2 received aerosolized PGE1 (5 [micro sign]g followed by 0.1 [micro sign]g [middle dot] kg-1 [middle dot] min-1) under mechanical ventilation combined with 5 cm H2 O positive end-expiratory pressure, and groups 3 and 4 received partial liquid ventilation with 15 ml/kg perflubron. Group 4 received a 5-[micro sign]g bolus followed by 0.1 [micro sign]g [middle dot] kg-1 [middle dot] min-1 PGE1 instilled intratracheally (not by aerosol) in combination with partial liquid ventilation. Measurements were performed at 30-min intervals for 120 min after lung injury.

Results: After lung injury, hypoxemia, hypercapnia, acidosis, and pulmonary hypertension developed in all animals and were sustained in groups 1 and 2 throughout the experiment. The partial pressure of oxygen in arterial blood of animals in group 3 improved with initiation of treatment, with statistical significance achieved at the 30 and 60 min time points as compared with controls. Group 4 animals had immediate and sustained increases in the partial pressure of oxygen in arterial blood that were significant compared with all other groups during the experiment. Statistically significant reductions in mean pulmonary artery pressure were seen only in group 4 animals compared with all other groups.     

Prevention of ventilator-induced lung injury with partial liquid ventilation

BACKGROUND/PURPOSE: Pulmonary injury from mechanical ventilation has been attributed to application of excess alveolar pressure (barotrauma) or volume (volutrauma). The authors questioned whether partial liquid ventilation (gas ventilation of the perfluorocarbon filled lung, PLV) would reduce ventilator-induced lung injury. METHODS: A tracheostomy tube and carotid artery catheter were placed in anesthetized Sprague-Dawley rats (500 +/- 50 g). Bovine serum albumin (BSA) labeled with Iodine (I) 125 was administered intraarterially. Ventilation with tidal volume (TV) of 5 mL/kg was initiated. The rats were then selected randomly to a 30-minute experimental period of one of the following ventilation protocols: continued atraumatic gas ventilation (GV, TV, 5 mL/kg; n = 10); atraumatic gas ventilation combined with intratracheal administration of 10 mL/kg perfluorocarbon (GV-PLV, TV, 5 mL/kg, n = 10); barotrauma (BT, peak inspiratory pressure [PIP], 45 cm H(2)O; n = 10); barotrauma with PLV (BT-PLV, PIP, 45 cm H(2)O; n = 8); volutrauma (VT, TV, 30 mL/kg; n = 8); or volutrauma with PLV (VT-PLV, TV, 30 mL/kg; n = 10). Animals were killed and the amount of radiolabeled BSA in both lungs was measured and normalized to the counts in 1 mL of blood from that animal (injury index). Data were analyzed by analysis of variance (ANOVA) with post-hoc t test comparison between groups. RESULTS: There was a significant difference in the (125)I-BSA injury index when all groups were compared (P <.001 by ANOVA). Post-hoc analysis showed a significant decrease in the injury index when comparing BT versus BT-PLV (P =.024) and VT versus VT-PLV (P =.014). CONCLUSION: (125)I-BSA leak produced during high-pressure or high-volume mechanical ventilation is reduced by partial liquid ventilation.     

Neutrophil Elastase Inhibitor, ONO-5046, Modulates Acid-induced Lung and Systemic Injury in Rabbits

Background: Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO-5046, before acid instillation.

Methods: Three groups of anesthetized rabbits (n = 12 in each group) underwent tracheostomies, and instillations were made into their right lower lobe airspaces with either phosphate buffered saline (pH, 7.4; volume, 1.2 ml/kg; n = 12) or HCl (pH, 1.25; volume, 1.2 ml/kg; n = 24). In half of the acid-instilled rabbits, ONO-5046,10 mg/kg, was given intravenously 15 min before the HCl instillation, and then 10 mg [center dot] kg sup -1 [center dot] h sup -1 of the drug was continuously infused throughout the experiment. The other groups of animals received the vehicle intravenously. Anesthesia and mechanical ventilation was continued for 8 h, whereas arterial blood gases were sampled intermittently. Eight hours after saline or acid instillation, the animals were killed, and their lungs, heart, kidneys, liver, and small intestines were harvested. Wet-to-dry weight ratios (W/D) and myeloperoxidase (MPO) assays of these organs were done, and elastase assays on the bronchoalveolar lavage fluids (BALF) obtained from each lung also were performed.

Results: Pretreatment with ONO-5046 attenuated the physiologic changes seen in the vehicle-treated animals. Significant decreases in W/D of the noninstilled lungs and of the small intestine and normalization of the oxygenation of the experimental animals occurred. The ONO-5046 pretreatment did not affect the neutrophil sequestration in the lungs or in the other organs as determined by neutrophil counts in BALF and by the MPO assays.     

Soluble Complement Receptor Type 1 Inhibited the Systemic Organ Injury Caused by Acid Instillation into a Lung

Background: Acid aspiration into one lung causes contralateral lung injury and systemic organ injury; this injury is thought to be mediated by the sequestration of activated neutrophils. Recombinant human soluble complement receptor 1 (sCR1) inhibits both the classical and alternative complement pathways; this study investigated the role of the complement system in unilateral acid lung injury by measuring the effects of administering sCR1 before or immediately after acid instillation.

Methods: Anesthetized rats (n = 18 in each group) underwent tracheostomy and insertion of a cannula into the anterior segment of the left lung. Then either 0.1 ml 0.1 N hydrochloric acid (HCl group) or 0.1 ml pH 7.4 phosphate buffered-saline (PBS group) was instilled. Fifteen minutes before (pre-sCR1 group) or 15 min after (post-sCR1 group) the acid was instilled, 10 mg/kg sCR1 was administered intravenously. Four hours after the acid instillation, rats were killed. In an additional 4 rats in each group, blood and bronchoalveolar lavage fluids obtained 1 h after the instillation of either acid or PBS were analyzed for tumor necrosis factor-alpha activity.

Results: The instillation of acid led to an increased wet-to-dry ratio of 5.2 +/- 0.1 in the acid-instilled lungs compared with their contralateral lungs (4.7 +/- 0.06). These values were greater than the values of 4.6 +/- 0.2 and 4.5 +/- 0.03 in the PBS-instilled lungs and their contralateral lungs, respectively (P < 0.05). The administration of sCR1 before or immediately after the instillation of acid did not attenuate the increase in the wet-to-dry ratio of the acid-instilled lungs. However, the small but consistent increase in the wet-to-dry ratio of the contralateral lungs was attenuated by the sCR1 infusions (P < 0.05). The instillation of acid increased the protein concentration in the bronchoalveolar lavage fluids from the injured lungs (1,000 +/- 206 micro gram/ml) compared with the protein concentration measured in the bronchoalveolar lavage fluids from their contralateral lungs (254 +/- 55 micro gram/ml). The administration of sCR1 before or immediately after the instillation of acid did not decrease the protein concentration in the bronchoalveolar lavage fluids from the acid-instilled lungs. The myeloperoxidase activity was increased in the acid-instilled lung, in their contralateral lung, and in the small intestines of the animals. The infusions of sCR1 before or immediately after the administration of acid led to significant decreases in the myeloperoxidase activities measured in the lungs and the intestines of the treated animals.

Plasma tumor necrosis factor-alpha activity was only increased (2.7 +/- 1.1 U/ml) in the animals that had received acid instillations. The infusions of sCR1, administered either before or immediately after the acid instillations, significantly decreased the measured tumor necrosis factor-alpha activity in the plasma (0.5 +/- 0.6. and 1.0 +/- 0.7 U/ml, respectively).     

Effect of terbutaline on alveolar liquid clearance after oleic acid-induced lung injury in rats

To investigate whether terbutaline affects alveolar liquid deorance after oleic acid-induced lung injury in rats. Methods ： Forty healthy Wistor rats （ weighing 250- 280 g） were randomly divided into five groups （ n = 8 in each group ） ： the normal control group （ control group ）, oleic acid injury group （injury group）, group （terbutaline group ）, terbutaline plus amiloridetreated group （ terbutaline ＋ amiloride group ） and terbutaline plus ouabaln-treated group （terbutaline ＋ ouabaln group）. Acute lung injury model was induced by intravenous oleic acid （0. 25 ml/kg body weight）. 24 hours later, 1.5 μCi^125 I-labeled 5% albumin solution （5 ml/kg body weight） was dripped into the lungs through trachea. The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter. Results： At24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia,with the alveolar liquid clearance rate decreased by 49. 2 % and the extravascnlar lung water content elevated by 47.9%. Compared with the rats in the injury group, terbutaline （ 10^-4 mol/L ） significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terlmtaUne was partly blocked by amiloride and ouabain, which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7 %, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7 % and 56. 8 %, respectively. Conclusions： Terbutaline can accelerate alveolar liquid clearance through increasing sodim transport to attenuate pulmonary edema, thus improving gas exchange, which may have therapeutical effect on pulmonary edema after acute lung injury.     

Small-dose perfluorocarbon reduces the recruitment pressure needed to open surfactant-deficient atelectatic lungs

BACKGROUND: This study was undertaken to investigate the effect of a small dose of perfluorocarbon on the recruitment pressure needed to open atelectatic lung areas. METHODS: In 12 Yorkshire pigs (body weight, 9 kg), lung injury was induced by whole lung lavage. After 1 h of conventional ventilation, an open lung maneuver was performed to obtain PaO2 values equal to the pre-lavage PaO2 values (+/-10%). After 1 h of ventilation at the lowest possible airway pressure that stabilized the recruited lung volume, the animals were disconnected from the ventilator to allow the lung to collapse. Six animals received a 5 ml/kg intratracheal dose of perfluorocarbon and a second open lung maneuver was performed. Six animals served as controls and received no perfluorocarbon but also underwent a second open lung maneuver. RESULTS: In both groups, an open lung maneuver resulted in a significant increase in oxygenation. The peak pressures needed to open the lung after 1 h of mechanical ventilation in the perfluorocarbon and control groups were 43.8 +/- 8.4 cmH2O and 46.6 +/- 4 cmH2O, respectively. The addition of perfluorocarbon significantly reduced the opening pressure to 34.5 +/- 6.3 cmH2O (P < 0.01), whereas the opening pressure in the control group, 45.0 +/- 0.2 cmH2O, did not change. CONCLUSION: The instillation of a small amount of perfluorocarbon significantly reduces the opening pressures needed to recruit atelectatic lung areas.     

Effect of PEEP and inhaled nitric oxide on pulmonary gas exchange during gaseous and partial liquid ventilation with small volumes of perfluorocarbon

BACKGROUND: Partial liquid ventilation, positive end-expiratory pressure (PEEP) and inhaled nitric oxide (NO) can improve ventilation/perfusion mismatch in acute lung injury (ALI). The aim of the present study was to compare gas exchange and hemodynamics in experimental ALI during gaseous and partial liquid ventilation at two different levels of PEEP, with and without the inhalation of nitric oxide. METHODS: Seven pigs (24+/-2 kg BW) were surfactant-depleted by repeated lung lavage with saline. Gas exchange and hemodynamic parameters were assessed in all animals during gaseous and subsequent partial liquid ventilation at two levels of PEEP (5 and 15 cmH2O) and intermittent inhalation of 10 ppm NO. RESULTS: Arterial oxygenation increased significantly with a simultaneous decrease in cardiac output when PEEP 15 cmH2O was applied during gaseous and partial liquid ventilation. All other hemodynamic parameters revealed no relevant changes. Inhalation of NO and instillation of perfluorocarbon had no additive effects on pulmonary gas exchange when compared to PEEP 15 cmH2O alone. CONCLUSION: In experimental lung injury, improvements in gas exchange are most distinct during mechanical ventilation with PEEP 15 cmH2O without significantly impairing hemodynamics. Partial liquid ventilation and inhaled NO did not cause an additive increase of PaO2.     

Partial liquid ventilation with perfluorodecalin following unilateral canine lung allotransplantation in non-heart-beating donors.

BACKGROUND: The purpose of this study was to evaluate canine lungs obtained from non-heart-beating donors after unilateral lung transplantation subjected to partial liquid ventilation with perfluorodecalin. METHODS: Twelve donor dogs were killed and kept under mechanical ventilation for 3 hours. Heart-lung blocks were harvested after retrograde pulmonary hypothermic flush with Perfadex. Left lung grafts were randomly transplanted into 12 weight-matched recipient animals. Animals were divided into 2 groups: control (standard mechanical ventilation, n = 6) and PLV (partial liquid ventilation, n = 6). Forty-five minutes after transplantation, the animals in the PLV group received perfluorodecalin (15 ml/kg) via orotracheal tube. All animals received volume-controlled ventilation (FIO2) 1.0, PEEP 5 cm H(2)O) over 6 consecutive hours. Thereafter, blood-gas analysis, ventilatory mechanics and hemodynamics were registered at 30-minute intervals. After 6 hours of reperfusion the animals were killed and the transplanted lungs were extracted to obtain the wet/dry weight ratio. RESULTS: There were significant differences in pulmonary arterial pressure, which were higher in control group animals (p < 0.009). The control animals also showed higher arterial PaO(2) than those in the PLV group (p < 0.00001), but lower PaCO(2) (p < 0.008). The peak and plateau pressures were higher in the PLV group (p < 0.00001). Neither static compliance nor wet/dry weight ratios were different in between groups. CONCLUSIONS: PLV with perfluorodecalin yields functional results compatible with life in this model. Nonetheless, pulmonary gas exchange and mechanics were superior after reperfusion in animals given conventional mechanical ventilation up to 6 hours after left lung allotransplantation.     

Systemic perfluorocarbons suppress the acute lung inflammation after gastric acid aspiration in rats

Perflurocarbons (PFCs) are used during liquid ventilation and as hemoglobin substitutes. PFCs reduce free radical generation and damage to the lung during liquid ventilation. Thus, we examined the effects of parenteral administration of PFCs on lung injury after acid aspiration. Rats were treated with intraperitoneal injection of either FC-77 or IV injection of Fluosol. Controls received intraperitoneal or IV normal saline (NS) before or at the time of injury and then were injured by instillation of NS + HCl (pH = 1.25) into their lungs via a tracheotomy. The animals were exposed to air or 98% oxygen, breathing spontaneously. The rats were injected with 0.05 microCi of (125)I-albumin (bovine serum albumin) before injury. The extent of lung injury was assessed 5 h postinjury by compliance and lung albumin permeability index measurement. Myeloperoxidase (MPO) activity and histologic examination were used to assess neutrophilic infiltration. Both FC-77 and Fluosol decreased the permeability index compared with controls (1.05 +/- 0.08; 1.08 +/- 0. 12, respectively, versus 1.34 +/- 0.21) and improved lung compliance after intratracheal instillation of 1.2 mL/kg of HCl/NS, pH = 1.25 + hyperoxia injury (P < 0.05). Lung MPO activity decreased in the FC-77 group and was associated with a concomitant decrease in neutrophil infiltration. MPO activity of the spleen increased after FC-77 treatment. The administration of FC-77 decreased the severity of lung permeability changes associated with acid in the presence or absence of hyperoxia exposure. These data suggest that attenuation of neutrophilic infiltration by PFCs decreases lung injury. IMPLICATIONS: Intraperitoneally administered perfluorocarbons in rats attenuate the neutrophilic infiltration in the lung after acid aspiration, thereby decreasing the alveolar protein leakage and improving pulmonary compliance.     

不同程度呼吸机相关性肺损伤大鼠血清CC10蛋白水平的比较

目的 比较不同程度呼吸机相关性肺损伤(VILI)大鼠血清CCIO蛋白的水平.方法 清洁级Wistar大鼠40只,雌雄不拘,体重200～250 g,随机分为5组(n=8),对照组(Ⅰ组)仅切开气管,不行机械通气;轻度肺损伤组(Ⅱ组)潮气量(VT)7 ml/kg,机械通气2 h;中度肺损伤组(Ⅲ组)VT 7 ml/kg,机械通气4 h;重度肺损伤组(Ⅳ组)VT 40 ml/kg,机械通气2 h;极重度肺损伤组(Ⅴ组)VT 40 ml/kg,机械通气4 h.Ⅰ组在气管切开后即刻,其余各组在机械通气结束时采集腹主动脉血3 ml,并收集支气管肺泡灌洗液(BALF),测定血清和BALF中CC10蛋白水平;观察肺Clara细胞;计算肺湿/干重比(W/D).结果 Ⅳ组和Ⅴ组终末细支气管、呼吸细支气管管腔有大量脱落Clara细胞,血管壁有大量漏出的CC10蛋白,其余组上述表现不明显;Ⅱ组～Ⅴ组血清CC10蛋白水平逐渐升高,肺组织损伤程度逐渐加重(P＜0.05);与Ⅰ组、Ⅱ组和Ⅲ组比较,Ⅳ组和Ⅴ组BALF中CC10蛋白水平降低(P＜0.05);血清CC10蛋白水平与肺组织损伤程度和肺W/D呈正相关,相关系数分别为0.915和0.846(P＜0.01);BALF中CC10蛋白水平与肺组织损伤程度和肺W/D呈负相关,相关系数分别为-0.799和-0.816(P＜0.01).结论 血清CC10蛋白水平与大鼠呼吸机相关性肺损伤程度有关.     

前列腺素E1在酸吸入性急性呼吸窘迫综合征中的肺保护作用

目的 研究静脉注射前列腺素E1（PGE1）能否阻止酸吸入性急性呼吸窘迫综合征（ARDS）的发生。方法 20只新西兰兔在稀HCI经右支气管滴入后随机分成两组：（1）损伤组（n＝10）在酸滴入后维持机械通气，未行其它治疗；（2）治疗组（n＝10）在酸滴入后即刻缓慢静注PGE1并维持。在基础状态及酸滴入后记录血气、气道压力并抽动脉血测定6－K－PGF1α、TXB2、NO^-2／NO^-3和ET－1，动物处死后测定右肺的湿干比（W／D）值及测定右肺支气管肺泡灌洗液（BALF）中总蛋白（TP）的水平，并作肺组织形态学观察。结果 治疗组在酸滴入后血氧分压（PaO2）显著高于损伤组。治疗组血浆6－K－PGF1α和NO^-2/NO^-3水平显著高于损伤组，而血浆TXB2和ET－1水平显著低于损伤组，治疗组右肺W／D和TP显著低于损伤组。损伤组右肺呈弥漫性损伤，而治疗则见损伤呈局灶治疗组右肺W／D和TP显著低于损伤组。损伤右肺呈弥漫性炎性损伤，而治疗组则见损伤呈局灶性，且其病理损伤程度较损伤组明显减轻。结论 （1）酸吸入后即刻应用PGE1可减轻ARDS的范围和严重程度；（2）PGE1保护了肺血管内皮细胞，使内源性PGI2／TXA2和NO／ET－1的产生保持平衡，有利地减轻ARDS。     

高频部分液体通气对吸入伤犬呼吸循环功能的影响

目的　观察高频部分液体通气 (highfrequencypartialliquidventilation ,HFPLV)对吸入性损伤犬肺力学、氧合和血流动力学参数的影响。　方法　 16条犬经吸入蒸气 ,造成重度吸入性损伤模型 ,并随机分为对照组和治疗组。两组动物致伤后均行高频喷射通气 (highfrequencyjetventila tiot,HFJV) ,治疗组同时经气管导管缓慢注入氟碳液体 (3ml/kg体重 ) ,行HFPLV治疗 ,于通气后3 0、60和 90min时测定两组动物血气、肺顺应性、气道阻力及血流动力学参数。　结果　治疗组PaO2 呈进行性上升 ,在各时相点与致伤后比较差异有显著性意义 (P <0 .0 5 ) ,而对照组各时相点与致伤后比较差异无显著性意义 (P >0 .0 5 ) ;治疗组PaCO2 也逐渐增高 ,于 60、90min显著高于致伤后水平 (P <0 .0 5 )。与对照组比较 ,治疗组各时相点的PaO2 稍有升高 (P >0 .0 5 ) ,PaCO2 于 90min显著增高 (P <0 .0 5 ) ,而两组动 /静态气道阻力、肺顺应性和血流动力学参数比较 ,差异均无显著性意义 (P >0 .0 5 )。　结论　HFPLV与单纯HFJV相比 ,更有利于吸入性损伤的动脉氧合 ,对血流动力学参数无明显不利影响