Partial Liquid Ventilation Group Research Articles

The Efficacy of Partial Liquid Ventilation on Lung Protection during Hypotension and Cardiac Arrest: Preliminary study for Lung Transplantation from Non-Heart Beating Donors

ackground: Because of the shortage of suitable brain-dead donors, the use of non–heart-beating donor lungs has been investigated experimentally. However, no effective lung protection method has been developed. In this study, we preliminarily investigated the protective effect of partial liquid ventilation (PLV) on a non–heart-beating rabbit lung. ethods: We used 20 male rabbits (mean weight, 3.7 kg) and divided them into 3 groups: the conventional ventilation (control) group, the PLV without cooling group, and the PLV with cooling group. After initially measuring donor cardiopulmonary function, we maintained hypotension at 50 mm Hg for 1 hour followed by 2-hour cardiac arrest. During this time, we used either conventional ventilation or PLV with or without cooling (4°C) for ventilation, and we evaluated the changes in arterial blood gas analysis, pulmonary resistance and elastance, tissue interleukin-8 (IL-8) concentration, and histologic damage. esults: We found no significant difference in arterial oxygen concentration or in carbon dioxide tension among the 3 groups in the hypotensive phase. Pulmonary elastance increased after perfusion of preservation solution in the control group. However, we found no change in elastance in the PLV groups, which was less than that in the control group. Histologic evaluation after perfusion of preservation solution revealed that alveolar structure was damaged significantly less and cell infiltration was milder in the PLV groups than in the control group. Although IL-8 concentrations in the controls increased after cardiac arrest, IL-8 in the PLV groups remained at baseline concentrations during the study period. onclusion: In this experimental model of hypotension and cardiac arrest, PLV suppresses lung injury when compared with gas-controlled ventilation. J Heart Lung Transplant 2005;24:723–9. Copyright © 2005 by the International Society for Heart and Lung Transplantation.

Partial liquid ventilation with perfluorodecalin following unilateral canine lung allotransplantation in non–heart-heating 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 blocs 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 (F io 2 1.0, PEEP 5 cm H 2O) 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 Pa o 2 than those in the PLV group ( p < 0.00001), but lower Pa co 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.

Continuous tracheal gas insufflation during partial liquid ventilation in juvenile rabbits with acute lung injury

To examine the hypothesis that combined treatment with tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) may improve pulmonary outcome relative to either treatment alone in acute lung injury (ALI), saline lavage lung injury was induced in 24 anesthetized, ventilated juvenile rabbits that were then randomly assigned to receive (n = 6/group) 1) conventional mechanical ventilation (CMV) alone, 2) continuous TGI at 0.5 l/min, 3) PLV with perfluorochemical liquid, and 4) combined TGI and PLV (TGI + PLV), and subsequently ventilated with minimized pressures and tidal volume (Vt) to keep arterial Po(2) (Pa(O(2))) >100 Torr and arterial Pco(2) (Pa(CO(2))) at 45-60 Torr for 4 h. Gas exchange, lung mechanics, myeloperoxidase, IL-8, and histomorphometry [including expansion index (EI)] were assessed. The CMV group showed no improvement in lung mechanics and gas exchange; all treated groups had significant increases in compliance, Pa(O(2)), ventilation efficacy index (VEI), and EI, and decreases in PaCO(2), oxygenation index, physiological dead space-to-Vt ratio (Vd/Vt), myeloperoxidase, and IL-8, relative to the CMV group. TGI resulted in lower peak inspiratory pressure, Vt, Vd/Vt, and greater VEI vs. PLV group; PLV resulted in greater compliance, Pa(O(2)), and EI vs. TGI. TGI + PLV resulted in decreased peak inspiratory pressure, Vt, Vd/Vt, and increased VEI compared with TGI, improved compliance and EI compared with PLV, and a further increase in Pa(O(2)) and oxygenation index and a decrease in PaCO(2) vs. either treatment alone. These results indicate that combined treatment of TGI and PLV results in improved pulmonary outcome than either treatment alone in this animal model of ALI.

Influence of partial liquid ventilation on bacterial growth and alveolar expansion in newborn rabbits with group B-streptococcal pneumonia.

Partial liquid ventilation (PLV) with perfluorocarbons has been considered as an alternative therapy for severe inflammatory lung disease. The present study was performed to test whether PLV influences bacterial growth and lung histology in a rabbit model of congenital pneumonia caused by group B streptococci. Near-term newborn rabbits were tracheotomized, inoculated via the airways with group B streptococci, and subsequently ventilated for 5 h with either PLV or conventional ventilation. At 30 min after group B streptococci administration, animals in the PLV group (n = 16) received 30 mL/kg body weight of perfluorocarbon (PF 5080) via the tracheal tube. Evaporative losses were substituted with 20 mL/kg perfluorocarbon at hourly intervals. Identical volumes of air were injected in control animals at the same times (n = 15). The number of colony-forming units in left lung homogenate, evaluated at the end of the experiments, tended to be lower in PLV-treated animals than in controls (6.8 x 109 versus 6.4 x 1010 colony-forming units/g body weight; p = 0.06). Comparison of these numbers with the colony-forming units injected at the beginning of the experiments revealed a reduction in bacterial number in the PLV group and proliferation in the controls (-2.2 x 108 versus +5.6 x 1010 colony-forming units/g body weight; p < 0.05). Histologic examination demonstrated less inflammation and more homogeneous lung expansion in PLV-treated animals. Two animals in the PLV group had focal interstitial emphysema. Our results suggest that PLV with PF 5080 reduces bacterial proliferation in experimental group B streptococcal pneumonia.

Partial liquid ventilation does not affect BALF TNF-, MIP-2, CINC-1 concentrations, or CD11b cell surface expression, but does increase macrophage proportion among BALF cells in the acute phase of rat LPS-induced lung injury.

To elucidate the mechanism of anti-inflammatory effect of partial liquid ventilation (PLV), cytokine concentration, surface CD11b, and macrophage expression were investigated in BALF. The 30-minutes group was treated with gas ventilation (GV) for 30 minutes after intratracheal LPS administration. The GV group was prepared in the same manner as the 30-minutes group, then the GV was continued for the following 2 hours. The PLV group was treated in the same manner as the 30-minutes group, and then received PLV with perflubron for the following 2 hours. Animals were euthanized to receive BAL. The PLV group showed a tendency to have a higher concentration than the GV group of TNF-alpha, MIP-2, and CINC-1 as measured by ELISA, although there were no significant differences. The ratio of expressions of CD11b and macrophages to total leukocytes were determined by flow-cytometry. There were no significant differences in the ratio of CD11b-positive expression to acquired cells (GV: 63.6 +/- 8.4%, PLV: 60.5+/-5.4%, P=0.73). However, the proportion of macrophages was significantly increased (GV: 5.6 +/-1.5, PLV: 14.0+/-1.3, P=0.006). These results suggest that the anti-inflammatory effect of PLV is not caused by the change in CD11b expression, and that PLV affects the proportion of macrophage among BALF cells.

Effect of partial liquid ventilation on bacterial clearance during Pseudomonas aeruginosa-induced lung injury in rats.

Partial liquid ventilation (PLV) has been shown to exhibit anti-inflammatory properties during non-infectious models of acute lung injury. The aim of this experimental study was to assess the effects of PLV on bacterial clearance during Pseudomonas aeruginosa-induced pneumonia in rats. The rats were assigned to four groups 4 h after bacterial challenge according to the kind of mechanical ventilation [gas ventilation (GV) or PLV, 6 ml/kg perflubron plus 2 ml/kg per h] and to the level of PEEP used (3 or 8 cm of water). Physiologic measures were recorded during anesthesia (arterial blood gases, airway and blood pressures) for 4 subsequent hours until sacrifice. No improvement of oxygenation was demonstrated in any group. The bacterial counts were higher in PLV-PEEP 8 rats compared to GV-PEEP 8 rats: median, 1.7.10(4) cfu (25th-75th percentiles, 1.2.10(4)-1.8.10(4)) versus 1.1.10(4) (8.7.10(3)-1.3.10(4))/ml of BAL fluid and 4.0.10(6) cfu (2.0.10(6)-5.5.10(6)) versus 1.7.10(6) cfu (9.7.10(5)-3.2.10(6))/ml of lung homogenate, respectively ( P<0.05, n=8/10 surviving rats per group). PEEP 8 was associated with a significant decrease in neutrophil recruitment in BAL fluid compared to PEEP 3 in both GV and PLV groups. Additional in vitro experiments demonstrated that perflubron induced a decrease in phagocytosis of P. aeruginosa by alveolar neutrophils. These results demonstrate that PLV is associated with an impaired bacterial clearance during early pneumonia in rats, which could have been favored by decreased bacterial phagocytosis by neutrophils.

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.

Effects of exogenous surfactant supplementation and partial liquid ventilation on acute lung injury induced by wood smoke inhalation in newborn piglets.

To investigate the beneficial effects of exogenous surfactant supplementation (ESS) and partial liquid ventilation (PLV) in treating acute lung injury induced by wood smoke inhalation. A prospective, randomized, controlled, multigroup study. An animal research laboratory at a medical center. Newborn piglets (n = 29; 1.80 +/- 0.06 kg) of either sex. Animals were ventilated with a tidal volume of 15 mL/kg, a rate of 30 breaths/min, a positive end-expiratory pressure of 5 cm H(2)O, and an Fio(2) of 1.0. After the induction of acute lung injury by wood smoke inhalation, animals were randomly assigned to receive either conventional mechanical ventilation (CMV) or PLV with or without ESS pretreatment. Animals were grouped as CMV, ESS-CMV, PLV, and ESS-PLV. Arterial blood gases, cardiovascular hemodynamics, dynamic lung compliance, and total lung injury scores were measured. After smoke inhalation, all four groups displayed similar high arterial carboxyhemoglobin levels, low Pao(2) (<150 mm Hg), and low dynamic lung compliance (<66% of its baseline). In the CMV group, these deleterious conditions remained during the 4-hr observation period, and severe lung injury was noted histologically. All treatment groups demonstrated a significant increase in Pao(2) compared with the CMV group. In addition, both the PLV and ESS-PLV groups displayed significant improvements in dynamic lung compliance and in their histologic outcomes. Nevertheless, none of the variables measured in the PLV group differed from those measured in the ESS-PLV group. In a newborn piglet model of smoke inhalation injury, PLV or ESS improved oxygenation. PLV compared favorably with ESS in its greater improvements in lung compliance and lung pathology. However, the combined therapy of ESS and PLV was not clearly superior to PLV alone during the observation period.

Liquid ventilation: Gas exchange, perfluorochemical uptake, and biodistribution in an acute lung injury.

OBJECTIVE: Compare the physiologic, histologic, and biochemical findings of tidal and partial liquid ventilation (PLV) with gas ventilated lambs with an acute lung injury. DESIGN: Experimental, prospective randomized controlled study. SETTING: School of medicine, department of physiology. SUBJECTS: Eighteen newborn lambs (</=1 wk old). INTERVENTIONS: Injury was established by using HCl saline lavages. Seven lambs underwent tidal liquid ventilation (TLV), five underwent PLV, and six underwent gas ventilation (GV) for 4 hrs. Measurements: Sequential arterial blood chemistries were performed. Ventilation efficiency index, arterial-alveolar Po(2), and physiologic shunt were calculated. Blood and tissue were analyzed for perfluorochemical fluid. Histologic examinations of lungs were performed. MAIN RESULTS: TLV oxygenation was significantly better (p <.001) than PLV and GV. Paco(2) was similar in all three groups. Ventilation efficiency index was significantly better (p <.01) in the TLV group as compared with the PLV and GV groups. Physiologic shunt was significantly less in the TLV injury group (p <.01) than the PLV and GV groups. Perfluorochemical fluid blood level of 2.3 +/- 0.32 &mgr;g/mL in the PLV group was significantly lower (p <.01) than TLV of 7.8 +/- 0.71 &mgr;g/mL; there was a difference (p <.01) as function of time in the TLV and no difference in the PLV injury group. There were no differences in tissue perfluorochemical fluid levels as a function of ventilation ([mean +/- sem] TLV, 219 +/- 26 &mgr;g/g; PLV injury, 184 +/- 26 &mgr;g/g). There was a significant difference in perfluorochemical fluid levels as a function of tissue (p <.001). CONCLUSION: In severe lung injury, this study demonstrates that physiologic gas exchange can be maintained with TLV or PLV. Physiologic shunt was less in the TLV group as compared with PLV or GV. Additionally, perfluorochemical fluid in the blood and tissue is low during PLV and TLV relative to that associated with intravenous administration of perfluorochemical fluid emulsion.

Partial liquid ventilation reduces release of leukotriene B4 and interleukin-6 in bronchoalveolar lavage in surfactant-depleted newborn pigs.

Perfluorocarbons have been shown to reduce the inflammatory process generated by alveolar macrophages in vitro. The aim of this study was to evaluate the impact of different ventilator modalities such as partial liquid ventilation (PLV), conventional ventilation (CV), and high-frequency oscillatory ventilation (HFOV) on the release of inflammatory mediators in vivo. Acute lung injury was induced in 30 male piglets by repeated saline lavage (arterial oxygen tension, <60 mm Hg; fraction of inspired oxygen, 1.0). Thereafter, animals were randomly assigned to one of five groups of six animals each: 1) 24 h of CV; 2) 24 h of CV plus surfactant therapy (S+CV); 3) 24 h of HFOV plus surfactant therapy (S+HFOV); 4) 1 h of PLV followed by 23 h of CV (PLV); and 5) 24 h of CV without previous lung injury (control group). Piglets randomized to S+CV or S+HFOV received natural surfactant (100 mg/kg). PLV with FC-77 was started in an initial dose of 30 mL/kg over 30 min followed by 0.5 mL x kg(-1) x min(-1) for another 30 min. After 1 h of PLV the animals were conventionally ventilated for 23 h. Before acute lung injury and after 24 h the number of inflammatory cells and the levels of IL-6, leukotriene B4, and tumor necrosis factor-alpha were measured in the bronchoalveolar lavage fluid. Additionally, the oxygenation index and the histopathologic damage were evaluated. Before acute lung injury, the number of inflammatory cells and the levels of mediators in bronchoalveolar lavage fluid were not different among the groups. After 24 h, the number of granulocytes in the PLV group was as low as in the control group. leukotriene B4 and IL-6 levels were found to be elevated in all groups except the control group (p < 0.01). The release of leukotriene B4 and IL-6 was lowest in the PLV group when compared with S+HFOV, S+CV, or CV (p < 0.05). No differences among the groups were detected for tumor necrosis factor-alpha. Although the concentrations of leukotriene B4 and IL-6 after PLV were lowest in the PLV group, histopathologic evidence of damage and the oxygenation index in the PLV group did not differ from that found in the S+CV or S+HFOV groups. In conclusion, PLV with perfluorocarbons may protect the lung from acute pulmonary inflammation more effectively than CV or HFOV does.

"Ideal PEEP" is superior to high dose partial liquid ventilation with low PEEP in experimental acute lung injury

To determine the effects of a high dose partial liquid ventilation (PLV) approximating the amount of the functional residual capacity (FRC) with low levels of positive end-expiratory pressure (PEEP) compared to a lung-protective strategy with volume-controlled mechanical ventilation (vcMV) with a PEEP level above the lower inflection point (LIP) on pulmonary gas exchange, haemodynamics, respiratory mechanics and lung injury in an experimental model of acute lung injury (ALI). Prospective, randomised, controlled study. Twenty-four anaesthetised, tracheotomised and mechanically ventilated (FIO(2) 1.0) pigs underwent induction of ALI by repeated saline wash-out of surfactant. Animals were randomly assigned to receive either PLV ( PLV, n=8) with 30 ml/kg of perfluorocarbons (PF 5080, 3 M, Germany) and a PEEP level of 5 cmH(2)O, to receive vcMV with a PEEP level of 1 cmH(2)O above the LIP ( (ideal) PEEP, n=8), or to receive vcMV with a PEEP level of 5 cmH(2)O ( Controls, n=8). Measurements of pulmonary gas exchange, respiratory mechanics and haemodynamics were performed hourly for a 6 h period. In the (ideal) PEEP group, intra-pulmonary shunt (Qs/Qt) decreased from 55+/-5% after induction of ALI to 10+/-3% ( p<0.05 versus Controls and versus PLV) and PaO(2) increased from 52+/-4 to 566+/-19 mmHg after 6 h of treatment ( p<0.05 versus Controls and versus PLV). In the PLV group, Qs/Qt decreased from 50+/-5% after induction of ALI to 24+/-3% ( p<0.05 versus Controls) and PaO(2) increased from 59+/-5 to 306+/-35 mmHg after 6 h of treatment ( p<0.05 versus Controls). In the PLV group and in Controls, mean pulmonary artery pressure (MPAP) was significantly increased from 27+/-2 to 38+/-2 mmHg and from 29+/-1 to 40+/-1 mmHg, respectively, 6 h after induction of ALI ( p<0.05 versus (ideal) PEEP), while in the (ideal) PEEP group, MPAP was maintained between 26+/-1 and 31+/-2 mmHg for 6 h after ALI. Cardiac output (CO) decreased significantly in the (ideal) PEEP group compared to Controls ( p<0.05), while CO did not change in the PLV group and in Controls. The compliance of the respiratory system (C(RS)) increased in the (ideal) PEEP group after induction of ALI from 11+/-2 to 22+/-5 ml/mbar ( p<0.05 versus Controls and versus PLV) and in the PLV group from 10+/-2 to 13+/-3 ml/mbar after 6 h of treatment ( p<0.05 versus Controls). On histological examination, the highest total injury scores were found in animals of the PLV group ( p<0.05 versus Controls and versus (ideal) PEEP), while the lowest total lung injury score was found in the dependent lung regions of the (ideal) PEEP group ( p<0.05 versus Controls). In this porcine model of ALI, vcMV with a PEEP level of 1 cmH(2)O above the LIP was superior to high dose PLV with a PEEP of 5 cmH(2)O in improving gas exchange and lung mechanics. In terms of lung damage, the treatment in the (ideal) PEEP group resulted in the lowest total lung injury scores.

Delayed partial liquid ventilation shows no efficacy in the treatment of smoke inhalation injury in swine.

In an earlier neonatal porcine model of smoke inhalation injury (SII), immediate postinjury application of partial liquid ventilation (PLV) had dramatic beneficial effects on lung compliance, oxygenation, and survival over a 24-h period. To explore the efficacy of PLV following SII, we treated animals at 2 and 6 h after SII and followed them for 72 h. Pigs weighing 8-12 kg were sedated and pharmacologically paralyzed, given a SII, and placed on volume-cycled, pressure-limited ventilation. Animals were randomized to three groups: group I (+SII, no PLV, n = 8), group II (+SII, PLV at 2 h, n = 6), and group III (+SII, PLV at 6 h, n = 7). Ventilatory parameters and arterial blood gasses were obtained at scheduled intervals. The PLV animals (groups II and III) followed a worse course than group I (no PLV); PLV groups had higher peak and mean airway pressures, oxygenation index, and rate-pressure product (a barotrauma index) and lower lung compliance and arterial partial pressure of oxygen-to-inspired oxygen fraction ratio (all P < 0.05). PLV conferred no survival advantage. The reported beneficial effects of PLV with other models of acute lung injury do not appear to extend to the treatment of SII when PLV is instituted in a delayed manner. This study was not able to validate the previously reported beneficial effects of PLV in SII and actually found deleterious effects, perhaps reflecting the predominance of airway over alveolar disease in SII.

Pulmonary administration of prostacyclin (PGI2) during partial liquid ventilation in an oleic acid-induced lung injury: inhalation of aerosol or intratracheal instillation?

The purpose of this study was to investigate the effects of aerosolized prostacyclin (A-PGI2) and intratracheally instilled prostacyclin (I-PGI2) during partial liquid ventilation (PLV) on gas exchange and pulmonary circulation in rabbits with acute respiratory distress. Prospective control study. A research laboratory at a university medical centre. Sixty-nine Japanese white rabbits. Lung injury was induced by oleic acid and the animals were divided into five groups of ten each: a mechanical gas ventilation (GV) group, an A-PGI2 group, a PLV group, an A-PGI2+PLV group and an I-PGI2+PLV group. PLV, A-PGI2+PLV and I-PGI2+PLV groups received 15 ml/ kg perflubron intratracheally while receiving mechanical GV. A-PGI2 and A-PGI2+PLV groups received aerosolized PGI2 (50 ng/kg/min) in combination with GV or PLV, respectively. The I-PGI2+PLV group was instilled 50 ng/kg/min PGI2 intratracheally in combination with PLV. After lung injury, all animals developed hypoxia, hypercarbia and pulmonary hypertension. The improvement of partial pressure of arterial oxygen (PaO2) in the A-PGI2 and PLV groups was transient, whereas the A-PGI2+PLV and I-PGI2+PLV groups showed consistent improvement throughout the experiment. The PaO2 values of the I-PGI2+PLV group were significantly higher than those of the other groups 120 min after treatment. The mean pulmonary artery pressure (PAP) significantly decreased after treatment in the A-PGI2, APGI2+PLV and I-PGI2+PLV groups. The results suggest that both aerosolized and intratracheally instilled PGI2 improve oxygenation and reduce PAP during PLV in oleic acid lung injury.

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

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. 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. 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. 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.

Intrapulmonary Instillation of Perfluorocarbon in Experimental Acute Lung Injury

Intrapulmonary Instillation of Perfluorocarbon in Experimental Acute Lung Injury Max et al.(page 1437) Max et al. used an experimental model to induce acute lung injury in 20 pigs to study the effects of partial liquid ventilation (PLV) with perfluorocarbon on the distribution of pulmonary blood flow. Gas exchange and hemodynamic and pulmonary blood flow were assessed in all animals before and after induction of acute lung injury with use of a saline lavage. Then, the animals were assigned randomly to one of two groups: a group of 10 who were submitted to PLV by administering 15 ml/kg of perfluorocarbon through the endotracheal tube at 1 and 2 h after injury, and a group of 10 in whom controlled mechanical ventilation was continued with no changes in respirator settings. Measurements were performed 1 and 2 h after injury in the latter group, as well. At specific points in the study protocol, researchers also injected radioactive-labeled macroaggregates of human serum albumin to enable measurement of pulmonary blood flow using single photon emission computed tomography. With use of specialized software, they generated 12 lung segments (four transaxial slices consisting of ventral, middle and dorsal segments) for each animal to be examined for distribution of blood flow. Arterial carbon dioxide tension increased from 32 ± 4 to 57 ± 13 mmHg after acute lung injury was induced, but, after the initial changes, arterial carbon dioxide tension and pH remained constant in groups 1 and 2. When all 20 pigs, either in gaseous ventilation or in PLV groups, were analyzed together, acute lung injury was shown to cause an increase of pulmonary blood flow to the ventral segment of slice 2 and to the middle segments of slices 1 and 2. Blood flow increased in the combined middle segments but decreased in the dorsal ones. Neither PLV nor gaseous ventilation resulted in a redistribution of blood flow to any of the 12 segments when values at 1 and 2 h after injury were compared with those measured immediately after acute lung injury. In a third group of five pigs, the attenuation control group, a similar number of lung lavages (11 ± 2) were needed to induce acute lung injury with an arterial oxygen tension of 52 ± 14 mmHg. Arterial oxygenation improved significantly after PLV with perfluororcarbon, which may be caused by an improvement in ventilation/perfusion ratios.

Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation

Purpose: The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. Materials and Methods: Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (Pao2 < 100 mm Hg). Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. Results: During the first IPSM, the PLV group showed a significant increase in Pao2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in Pao2 with PEEP. The control and EP groups showed improvement in Pao2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase Pao2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP, peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). Conclusion: PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation. Copyright © 2000 by W.B. Saunders Company

High-frequency oscillatory ventilation and partial liquid ventilation after acute lung injury in premature lambs with respiratory distress syndrome.

Conventional mechanical ventilatory support (CV) contributes to lung injury in premature lambs with respiratory distress syndrome, a disease that is characterized by progressive deterioration of gas exchange and increased lung inflammation. Lung recruitment strategies, such as high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV), improve gas exchange and attenuate lung inflammation when instituted immediately after birth. However, whether these recruitment strategies are effective as rescue treatment after established lung injury is unknown. To determine the separate and combined effects of HFOV and PLV when initiated after the establishment of acute lung injury in severe respiratory distress syndrome, we studied the effects of these strategies on gas exchange and histologic signs of acute lung injury in premature lambs. Animals were intubated, treated with surfactant and ventilated with 1.00 FIO2 for 4 hrs. After 2 hrs, animals were either continued on CV (controls) or treated with one of three strategies: HFOV; CV + PLV; or HFOV + PLV. The response to low-dose inhaled nitric oxide (5 ppm) was measured in each group at the end of the study. An animal laboratory affiliated with University of Colorado School of Medicine. A total of 20 premature lambs at 115-118 days of gestation (term = 147 days). In comparison with control animals, each of the rescue therapies improved PaO2 after 1 hr of treatment. The HFOV and HFOV + PLV groups had higher PaO2 than CV + PLV or CV alone (p < .05). Mean airway pressure (Paw) was lower in the PLV groups during CV or HFOV compared with their controls (p < .05). Inhaled NO improved PaO2 in all groups; however, the increase in PaO2 was greatest in the HFOV + PLV group (p < .05). Histologic examination and myeloperoxidase assay were not different between groups. We conclude that each lung recruitment strategy improved oxygenation in premature lambs with established lung injury.

Effect of partial liquid ventilation on pulmonary vascular permeability and edema after experimental acute lung injury.

We evaluated the effects of partial liquid ventilation (PLV) with two different dosages of the perfluorocarbon LiquiVent (perflubron) on pulmonary vascular permeability and edema formation after oleic acid (OA)-induced acute lung injury in dogs. We used imaging with positron emission tomography to measure fractional pulmonary blood flow, lung water concentration (LWC), and the pulmonary transcapillary escape rate (PTCER) of (68)Ga-labeled transferrin at 5 and 21 h after lung injury in five dogs undergoing conventional mechanical ventilation (CMV), five dogs undergoing low-dose PLV (perflubron at 10 ml/kg), and four dogs undergoing high dose PLV (perflubron at 30 ml/kg). A positive end-expiratory pressure of 7.5 cm H(2)O was used in all dogs. After OA (0.08 ml/kg)- induced lung injury, there were no significant differences or trends for PTCER or LWC at any time when the PLV groups were compared with the CMV group. However, lung tissue myeloperoxidase activity was significantly lower in the combined PLV group than in the CMV group (p = 0.016). We conclude that after OA-induced lung injury, the addition of PLV to CMV does not directly attenuate pulmonary vascular leak or lung water accumulation. Rather, the benefits of such treatment may be due to modifications of the inflammatory response.

Surfactant and partial liquid ventilation via conventional and high-frequency techniques in an animal model of respiratory distress syndrome.

OBJECTIVE: To compare the physiologic and pathologic effects of conventional ventilation (CV) and high-frequency ventilation (HFV) during partial liquid ventilation (PLV) with perflubron after surfactant treatment with the results of HFV plus surfactant in an animal lung-injury model created by saline lavage. We also studied the dose effects of perflubron during HFV. DESIGN: Randomized experimental study. SETTING: Research animal laboratory. SUBJECTS: A total of 32 newborn piglets. INTERVENTIONS: After lung injury was induced, the animals were randomized to one of four groups: a) CV + surfactant + perflubron to functional residual capacity (FRC); b) HFV + surfactant + perflubron to FRC; c) HFV + surfactant + 10 mL/kg perflubron; and d) HFV + surfactant. All then received intratracheal surfactant. After 30 mins, perflubron was administered to the PLV groups. The animals underwent ventilation for 20 hrs. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and hemodynamic variables were continuously monitored. Pulmonary histologic and morphometric analyses were performed after death or euthanasia at 20 hrs. All animals had sustained improvements in arterial/alveolar oxygen ratios, and no differences were observed among groups. All HFV groups required higher mean airway pressures to maintain oxygenation (p <.05). Hemodynamics did not differ among groups. Pathologic analysis demonstrated decreased lung injury in both cranial-dorsal (nondependent) and caudal-ventral (dependent) lobes of all animals treated with PLV when compared with those treated with HFV + surfactant (p <.05). CONCLUSIONS: After surfactant treatment, physiologic support over 20 hrs was similar during HFV with or without perflubron and CV with perflubron. All PLV modalities improved lung pathologic factors uniformly to a greater degree than did HFV + surfactant. A lower treatment volume of perflubron during HFV produced physiologic and pathologic results similar to those produced by perflubron with respect to FRC during either CV or HFV.

Comparison of Exogenous Surfactant Therapy, Mechanical Ventilation with High End-Expiratory Pressure and Partial Liquid Ventilation in a Model of Acute Lung Injury

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.