BACKGROUND: We examined the effects of varying inspiratory to expiratory (I : E) ratio on gas exchange and hemodynamics during high frequency partial liquid ventilation (HFPLV), a combination of high frequency ventilation (HFV) and partial liquid ventilation (PLV), in a rabbit model of acute lung injury. METHODS: Twelve rabbits treated with repeated saline lavage were divided into two groups. In the HFPL group (n = 6), 6 ml/kg of perfluorodecaline was administered through the endotracheal tube. Rabbits in this group and in the HFJ group (n = 6) were treated with high frequency jet ventilation (HFJV) at I : E ratios of 1 : 1, 1 : 2, and 1 : 3 for 15 minutes, and arterial blood gas, mixed venous blood gas and hemodynamic parameters were measured. RESULTS: We observed no significant respiratory and hemodynamic differences between the two groups. At an I : E ratio of 1 : 1, the PaO2 was significantly higher, and the shunt rate and PaCO2 were significantly lower in both groups, compared with I : E ratios of 1 : 2 and 1 : 3. Cardiac output at the 1 : 3 I : E ratio was significantly higher than at 1 : 1. CONCLUSIONS: These findings indicate that, in this model, a 1 : 1 I : E ratio was superior for oxygenation and ventilation than I : E ratios of 1 : 2 or 1 : 3, while having no detrimental effects on hemodynamics.
Acute Lung Injury ; Cardiac Output ; Hemodynamics ; High-Frequency Jet Ventilation ; High-Frequency Ventilation ; Liquid Ventilation ; Oxygen ; Rabbits ; Therapeutic Irrigation ; Ventilation

BACKGROUND: The opitmal ventilator setting during partial liquid ventilation(PLV) is controversial. This study investigated the effects of various gas exchange parameters during PLV in normal rabbit lungs in order to aid in the development of an optimal ventilator setting during PLV. METHODS: Seven New-Zealand white rabbits were ventilated in pressure-controlled mode with the following settings; tidal volume(VT) 8ml/kg, positive end-expiratory pressure(PEEP) 4cmH2O, inspiratory-to-expiratory ratio(I:E ratio) 1:2, fraction of inspired oxygen(F1O2) 1.0. The respiration rate(RR) was adjusted to keep PaCO2 between 35~45mmHg. The ventilator settings were changed every 30 min in the following sequence : (1) Baseline, as the basal ventilator setting, (2) Inverse ratio, I:E ratio 2:1, (3) high PEEP, adjust PEEP to achieve the same mean inspiratory pressure (MIP) as in the inverse ratio, (4) High VT, VT 15ml/kg, (5) high RR, the same minute ventilation(MV) as in the High VT. Subsequently, the same protocol was repeated after instilling 18ml/kg of perfluorodecalin for PLV. The parameters of gas exchange, lung mechanics, and hemodynamics were examined. RESULTS: (1) The gas ventilation(GV) group showed no significant changes in the PaO2 at all phases. The PaCO2 was lower and the pH was higher at the high VT and high RR phases(p<0.05). No significant changes in the lung mechnics and hemodynamics parameters were observed. (2) The baseline PaO2 for the PLV was 312+/-113mmHg. This was significantly lower when decreased compared to the baseline PaO2 for GV which was 504+/-81mmHg(p=0.001). During PLV, the PaO2 was significantly higher at the high PEEP(452+/-38mmHg) and high VT(461+/-53mmHg) phases compared with the baseline phase. However, it did not change significantly during the inverse I:E ratio or the high RR phases. (3) The PaCO2 was significantly lower at high VT and RR phases for both the GV and PLV. During the PLV, PaCO2 were significantly higher compared to the GV (p<0.05). (4) There were no important or significant changes in of baseline and high RR phases lung mechanics and hemodynamics parameters during the PLV. CONCLUSION: During PLV in the normal lung, adequate VT and PEEP are important for optimal oxygenation.
Hemodynamics ; Hydrogen-Ion Concentration ; Liquid Ventilation* ; Lung* ; Mechanics ; Oxygen ; Physiology ; Rabbits ; Respiration ; Ventilators, Mechanical

OBJECTIVETo observe the pathological change of partial liquid ventilation (PLV) through establishing the rabbit model of acute lung injury (ALI) induced by meconium aspiration.

METHODSAdult, healthy male or female New Zealand white rabbits were randomly allocated into six groups as follows: (1) control group, (2) conventional mechanical ventilation (CMV) group, (3) high-frequency oscillatory ventilation (HFOV) group, (4) CMV combined with PLV group, (5) HFOV combined with PLV group and (6) normal group. The animals were anesthetized with 1% pentobarbital and tracheotomy was performed and endotracheal tube was placed, 20% meconium fluid (3 ml/kg) was quickly injected into the lung through the endotracheal tube and arterial blood gas was analyzed 30 minutes later. ALI was indicated when P/F ratio (PaO2)/FiO(2)) was < or = 300 mm Hg (1 mm Hg = 0.133 kPa) and Cdyn Dynamic Compliance declined by more than 30% of the baseline. The animals were then randomly allocated into one of the 6 groups. In PLV groups (including CMV + PLV and HFOV + PLV) warmed (37 degrees C) and oxygenated perfluorocarbon was slowly instilled into the lungs of the rabbits through the endotracheal tube at a low-dose 3 ml/kg, then set 15-min positive pressure by sacculus proprius to guarantee perfluorocarbon to steadily diffuse in to the lungs. Six hours after ventilation the animals were sacrificed by using overdose of room air instillation via vein. The lungs were taken and fixed in 4% paraformaldehyde (PFA) and were stained with hematoxylin-eosin (HE). Pathological evaluations included inflammatory manifestation, edema and hemorrhage in both alveolar and interstitial area, damages of small airway (alveolar tube and alveolar bursa) and hyaline membrane formation. One way analysis of variance, Student Newman-Keuls (SNK) method and Kruskal-Wallis (K-W) test were used for comparisons.

RESULTSWith the exception of normal group 30 minutes after meconium injections blood gas analysis in different groups showed significant changes and PaO(2)/FiO(2) (< 300 mm Hg), Cdyn declined by more than 60% compared with baseline (P < 0.05). The pathological analysis showed that alveolar and interstitial inflammation, edema, alveolar and interstitial hemorrhage, and small airway damage existed in each group. The hyaline membrane formation was found in one of CMV + PLV group rabbits. The perfluorocarbon-treated animals (CMV + PLV and HFOV + PLV) showed significantly less injury in dependent lung and less damage of small airway (CMV + PLV or HFOV + PLV vs. CMV = 1.1 +/- 0.4 or 0.9 +/- 0.3 vs 2.6 +/- 0.5) compared with the animals of CMV group (P < 0.01). HFOV group (2.1 +/- 0.3) also had less alveolar and interstitial inflammation compared with CMV group (3.0 +/- 0) (P < 0.05), and there was less evidence of alveolar and interstitial edema in the animals treated with HFOV + PLV (1.0 +/- 0.7) compared with CMV (2.0 +/- 0.8) (P < 0.01). Treatment with perfluorocarbon did not result in significant difference in alveolar and interstitial hemorrhage. Compared with CMV and HFOV groups, the groups treated with PLV showed lower mortality of animals (21.4% and 14.3%).

CONCLUSIONSPLV can alleviate the histological damage of acute lung injury induced by meconium aspiration and increased survival chance and therefore PLV would be a useful treatment for MAS. The effectiveness and safety of application of PLV should be evaluated in clinical studies.

Acute Lung Injury ; etiology ; pathology ; Animals ; Animals, Newborn ; Disease Models, Animal ; Female ; Liquid Ventilation ; Male ; Rabbits

BACKGROUNDPediatric patients are susceptible to lung injury that does not respond to traditional therapies. Partial liquid ventilation (PLV) has been developed as an alternative ventilatory strategy for treating severe lung injury. The aim of this study is to investigate the effect of PLV on lung function in immature piglets.

METHODSAcute lung injury was induced in 12 Chinese immature piglets by oleic acid (OA). The animals were randomly assigned to two groups (n = 6 each group): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. Mean arterial blood pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), left atrial pressure (LAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), cardiac output (CO), mean pressure of airway (Paw), dynamic lung compliance (Cydn), and arterial blood gases were measured during the observation period.

RESULTSNo piglet died in either group with severe lung injury. After four hours of ventilation, pH in the MV group gradually decreased to lower than 7.20, while in the PLV group, pH also gradually decreased but remained higher than 7.20 (P < 0.05). Partial pressure of oxygen in artery (PaO2) decreased in both groups, but with a significant difference between the PLV group and MV group (P < 0.05). Partial pressure of carbon dioxide in artery (PaCO2) increased in both groups, but with a significant difference between the PLV group and MV group (P < 0.05). Paw increased in both groups, but was not significantly different (P > 0.05). Cydn decreased in both groups, but without a significant difference (P > 0.05). At four hours, heart rate (HR) and MAP in both groups decreased. MPAP in both groups increased, and there was a significant difference between the two groups (P < 0.05). CVP was stable in both groups. At four hours, PVR and LAP were increased in both groups. CO was decreased in both groups (P < 0.05). SVR was stable during the observation time.

CONCLUSIONPLV did not improve outcome in changes of lung function.

Animals ; Liquid Ventilation ; Lung Injury ; chemically induced ; therapy ; Oleic Acid ; Swine

PURPOSE: To evaluate gas exchange, hemodynarnics and pulmonary function during partial liquid ventilation(PLV) using PFC(perfluorodecalin), compared with conventional gas ventilation in newborn piglets with saline lavage-induced respiratory distress. METHODS: In a total of 16 instrumented and ventilated piglets, acute respiratory distress(below 70 mmHg of PaOz at FiOz 1.0) was induced by repeated saline pulmonary lavage. The piglets were randomized to receive either gas ventilation only(control group, n=8) or PLV(PLV group, n=8) by 3 consecutive intratracheal instillations of 10mL/kg of perfluorodecalin at lavage baseline and at 30, 60min after lavage. All animals were mechanically ventilated for 150min after lavage with time-cycled pressure-limited gas ventilation, a peak inspiratory pressure of 30cm HO, frequency of 30breaths/min, FiO;, 1.0 and a positive end-expiratory pressure of 4cm HzO. All measurements were made at 30inin interval afterwards to 150rnin after lavage. RESULTS: All animals developed severe hypoxemia, hypercarbia, and acidosis due to increased transpulmonary shunt fraction after saline lavage, which persisted during the experiments in control group. PaOz significantly increased with increases in dosage of PFC from 56+/-6 to 235+/-90 mmHg and PaCOz also significantly decreased in the PLV group. Venous admixture and pH showed significant differences between the two groups. Pulmonary dynamic cornpliance, tidal volume and mean airway resistance were also significantly improved in the PLV group. However, hemodynamic parameters were similar in both groups. CONCLUSION: PLV with perfluorodecalin irnproves gas exchange and pulmonary function in newborn piglets with saline lavage-induced respiratory distress.
Acidosis ; Airway Resistance ; Animals ; Anoxia ; Hemodynamics* ; Humans ; Hydrogen-Ion Concentration ; Infant, Newborn* ; Liquid Ventilation* ; Positive-Pressure Respiration ; Therapeutic Irrigation ; Tidal Volume ; Ventilation

Combined Modality Therapy ; High-Frequency Ventilation ; Humans ; Liquid Ventilation ; Nitric Oxide ; therapeutic use ; Pulmonary Surfactants ; therapeutic use ; Respiration, Artificial ; Respiratory Insufficiency ; therapy

PURPOSE: Repair of congenital diaphragmatic hernias (CDH) has changed from an urgent procedure to a delayed procedure during the last decade. Recently, several new therapeutic methods have been suggested, such as extracorporeal membrane oxygenation, high frequency oscillatory ventilation, partial liquid ventilation, nitric oxide (NO) inhalation, surfactant therapy, and fetal tracheal ligation. Despite recent approaches, CDH remains an unsolved problem with a mortality rate of 35% to 50%. We evaluated the clinical manifestations and the outcomes of newborns that had a Bochdalek hernia. METHODS: The charts of all neonates with a Bochdalek hernia who had been treated at the Division of Pediatric Surgery, Asan Medical Center, from May 1989 to December 1999 were reviewed (n=32). The following para meters were analyzed for survival; gestational age, birth weight, the presence of associated anomalies, the side of defect, the presence of a sac, the position of the stomach, the age at surgery, the availability of high frequency ventilation therapy, and the availability of NO inhalation therapy (1998-1999). RESULTS: Overall, 20 of the 32 newborns survived (62.5%). The average age at gestation was 269 days (range: 202 to 288 days). The average weight at birth was 2,800 gram (range: 856-4,000 grams). There were seven major anomalies. Six patients died without repair. The average age at repair was 39.8 hours (range: 0.5 to 168 hours). The defect was left sided in 23 cases (88.5%). Four had hernia sacs. The stomach had herniated into the chest in 7 of 26 cases. Since 1998, the survival rate has been 7/10 (70.0%). The significant prognostic factors were birth weight and the presence of major anomalies (p<0.05). CONCLUSION: Birth weight and the presence of major anomalies had a significant effect on survival. In neonates with CDH, and careful long-term follow up is required to evaluate strategies using high frequency ventilation and inhaled NO.
Birth Weight ; Chungcheongnam-do ; Extracorporeal Membrane Oxygenation ; Gestational Age ; Hernia* ; Hernia, Diaphragmatic ; High-Frequency Ventilation ; Humans ; Infant, Newborn* ; Inhalation ; Ligation ; Liquid Ventilation ; Mortality ; Nitric Oxide ; Parturition ; Pregnancy ; Respiratory Therapy ; Stomach ; Survival Rate ; Thorax ; Ventilation

BACKGROUND: Liquid ventilation is associated with decreased inflammatory response in an injured lung. This study was performed to investigate if whether perfluorocarbon (PFC) can decrease chemokine expression in airway epithelial cells. METHODS : A549 cells were used for airway epithelial cells and perfluorodecalin for PFC. To expose cells to PFC, lower chamber of Transwell a plate was used. This study was performed in two parts. In the first part, we examined whether PFC could decrease chemokine expression in airway epithelial cells through inhibition of other inflammatory cells. Peripheral blood mononuclear cells (PBMC's) were isolated and stimulated with lipopolysaccharide (LPS, 10 mg/mL) for 24 hours with or without exposure to PFC. Then A549 cells were stimulated with conditioned media (CM) containing the culture supernatants of PBMC . After 24 hours, the expressions of interleukin-8 (IL-8) and RANTES were measured. In the second part of the study, we studied whether PFC could directly suppress chemokine expression in airway epithelial cells. A549 cells were stimulated for 24 hours with interleukin-1b and/or tumor necrosis factor-a with or without exposure to PFC (,)and then the chemokine expression was measured. Northern analysis was used to measure the mRNA expression (,) and ELISA was used for immunoreactive protein measurements in culture supernatant. RESULTS: 1. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by CM from LPS-stimulated PBMC in A459 cells compared with CM from unstimulated PBCM(p<0.05) (,)but exposure of PFC had no significant effect on either mRNA expression immunoreactive protein expression. 2. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by IL-1b and TNF-a in A549 cells(p<0.05)(,)but exposure of PFC had no significant effect on either mRNA expression or immunoreactive protein production. CONCLUSION: Decreased chemokine expression of airway epithelial cells may not be involved in decreased inflammatory response observed in liquid ventilation. Further studies on possible mechanisms of decreased inflammatory response are warranted.
Chemokine CCL5 ; Culture Media, Conditioned ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells* ; Inflammation ; Interleukin-8 ; Liquid Ventilation ; Lung ; Necrosis ; RNA, Messenger

OBJECTIVETo investigate the influence of high frequency partial liquid ventilation (HFJV) on the cardiopulmonary function in dogs with inhalation injury.

METHODSSixteen mongrel dogs inflicted by hot steam inhalation were subjected to severe inhalation injury and were randomly divided into control (C) and treatment (T) groups. The dogs in both groups were all given HFJV. In addition, the dogs in T group were simultaneously supplied with perfluorocarbon liquid (3 ml/kg) into the lungs slowly via tracheal intubation for liquid ventilation. The blood gas analysis, pulmonary compliance, airway resistance and hemodynamic parameters were determined at 30, 60 and 90 minutes after ventilation.

RESULTSThe PaO(2) in T group increased progressively, which was significantly higher than the post-injury value at all time points (P < 0.05). While the PaO(2) in C group exhibited no difference to the post-injury value at all time points. The PaCO(2) in T group increased obviously and was higher than the post-injury value at 60 and 90 post-ventilation minutes (P < 0.05). Furthermore, the PaO(2) in all the time points in T group was a little higher than that in C group (P > 0.05) and PaCO(2) in T group was much higher than that in C group at 90 min after ventilation (P < 0.05). But there was no difference between the two groups in terms of dynamic/static pulmonary compliance and airway resistance as well as the hemodynamics.

CONCLUSIONCompared with simple HFJV, high frequency partial liquid ventilation seemed to be beneficial to the oxygenation after inhalation injury and to be no influence on the hemodynamics.

Airway Resistance ; Animals ; Blood Gas Analysis ; Burns, Inhalation ; physiopathology ; therapy ; Dogs ; Female ; High-Frequency Jet Ventilation ; Liquid Ventilation ; Lung Compliance ; Male ; Pulmonary Circulation ; Pulmonary Gas Exchange ; Respiration, Artificial ; methods ; Respiratory Function Tests ; Time Factors

BACKGROUND: Partial liquid ventilation (PLV) and prone positioning can improve the arterial oxygenation (PaO2) in acute lung injury (ALI). We evaluated the effect of prolonged prone positioning during partial liquid ventilation (PLV) in a canine model of acute lung injury. METHODS: Six mongrel dogs (weighing 17.4 +/- 0.7 kg each) were anesthetized, intubated and mechanically ventilated. After 1 hour of baseline stabilization, the dogs' lungs were instilled with 40 mL/kg perfluorocarbon (PFC). PLV was first performed in the supine position for 1 hour (S1), then in the prone position for 3 hours with hourly measurements (P1, P2, P3), and finally, PLV was performed with the animal turned back to the supine position for 1 hour (S2). RESULTS: After instillation of the PFC, the PaO2 significantly increased from 99.2 +/- 32.6 mmHg at baseline to 198.1 +/- 59.2 mmHg at S1 (p=0.001). When the dogs were turned to the prone position, the PaO2 further increased to 288.3 +/- 80.9 mmHg at P1 (p=0.008 vs. S1) : this increase was maintained for 3 hours, but the PaO2 decreased to 129.4 +/- 62.5 mmHg at S2 (p< 0.001 vs. P3). Similar changes were seen in the shunt fraction. There were no significant differences for the systemic hemodynamic parameters between the prone and supine positions. CONCLUSION: Prolonged prone positioning during PLV in an animal model of ALI appears to improve oxygenation without any hemodynamic compromise.
Animals ; Dogs ; Liquid Ventilation/*methods ; Models, Animal ; Prone Position/*physiology ; Pulmonary Gas Exchange/*physiology ; Research Support, Non-U.S. Gov't ; Respiratory Distress Syndrome, Adult/physiopathology/*therapy