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Biomedical subjects

B P Fuhrman

Publications and source records attributed to B P Fuhrman.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

OBJECTIVE: To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. DESIGN: A prospective, randomized, controlled, in vivo animal laboratory study. SETTING: Animal research facility of a health sciences university. SUBJECTS: Forty-six New Zealand White rabbits. INTERVENTIONS: Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. MEASUREMENTS AND MAIN RESULTS: Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. CONCLUSIONS: Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.

Animals↗
PubMed2000

Partial liquid ventilation with perflubron attenuates in vivo oxidative damage to proteins and lipids.

OBJECTIVE: To determine the impact of partial liquid ventilation on the degree of pulmonary damage by reactive oxygen species in a model of acute lung injury caused by systemic endotoxemia. DESIGN: A prospective, controlled, in vivo, animal laboratory study. SETTING: Animal research facility of a health sciences university. SUBJECTS: Forty New Zealand White rabbits. INTERVENTIONS: Mature rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Animals were assigned to receive either partial liquid ventilation (n = 16) with perflubron (18 mL/kg via endotracheal tube) or conventional mechanical ventilation (n = 16). Both groups were ventilated using similar strategies, with an Fio2 of 1.0 and tidal volume as required to obtain a normal Paco2. Animals were then given 0.9 mg/kg Escherichia coli endotoxin intravenously over 30 mins. Eight uninjured instrumented and mechanically ventilated animals served as controls. Partial liquid ventilation or conventional ventilation was continued for 4 hrs before the animals were killed. Lung homogenates were analyzed for malondialdehyde (MDA) and 4-hydroxy-2(E)-nonenal (4-HNE) concentrations using a colorimetric assay. To assess protein oxidative damage, carbonyl groups in protein side chains were derivatized with 2,4-dinitrophenylhydrazine followed by Western blotting with a dinitrophenylated-specific primary antibody. MEASUREMENTS AND MAIN RESULTS: MDA (713.42+/-662 vs. 1601.4+/-1156 nmol/g protein; p = .023) and MDA plus 4-HNE (1480.24+/-788 vs. 2675.2+/-1628 nmol/g protein; p = .038) concentrations were lower in animals treated with partial liquid ventilation compared with conventionally ventilated animals, respectively. Animals treated with partial liquid ventilation exhibited attenuation of dinitrophenylated-derivatized protein bands by Western blotting, indicating a reduction in protein oxidative damage. The presence of perfluorocarbon did not interfere with the MDA assay when assessed by independent analysis in vitro. Perflubron did not serve as a sink for peroxyl radicals produced in the aqueous phase during separate in vitro oxidation experiments. CONCLUSIONS: Partial liquid ventilation attenuates oxidative damage to lipids and proteins during experimental acute lung injury. This finding is not caused by binding of lipid peroxidation products to perflubron or by the peroxyl radical scavenging properties of perflubron.

Animals↗
PubMed1999

Liquid ventilation attenuates pulmonary oxidative damage.

PURPOSE: Liquid perfluorochemicals reduce the production of reaction oxygen species by alveolar macrophages. We sought to determine whether the use of liquid perfluorochemicals in vivo during liquid ventilation would attenuate oxidative damage to the lung. MATERIALS AND METHODS: Healthy infant piglets (n = 16) were instrumented for mechanical ventilation and received intravenous oleic acid to create an acute lung injury. The animals were assigned to a nontreatment group receiving conventional mechanical ventilation or a treatment group receiving partial liquid ventilation with a liquid perfluorochemical. Following sacrifice, the bronchoalveolar lavage and lung parenchyma were analyzed for evidence of oxidative damage to lipids and proteins by determination of TBARS and carbonylated protein residues, respectively. RESULTS: Mortality in the control group was 50% at the completion of the study compared with no deaths in the partial liquid ventilation group (P = .025). The alveolar-arterial oxygen difference was more favorable following injury in the partial liquid ventilation group. The liquid ventilation group demonstrated a 32% reduction in TBARS (P = .043) and a 14% reduction in carbonylated protein residues (P = .061). CONCLUSION: These data suggest that partial liquid ventilation supports gas exchange and reduces mortality in association with a reduction in the production of reactive oxygen species and the concomitant attenuation of tissue damage during the early phase of acute lung injury.

Animals↗
PubMed1999

Partial liquid ventilation influences pulmonary histopathology in an animal model of acute lung injury.

PURPOSE: The aim of this study was to assess the effect of partial liquid ventilation (PLV) and conventional mechanical ventilation (CMV) in the pattern of distribution of lung injury in a rabbit model of acute lung injury. MATERIALS AND METHODS: Animals (1.5 to 3.5 kg) were assigned to receive CMV (tidal volume of 10 mL/kg and a PEEP of 5 cm H2O) or PLV with 18 mL/kg of intratracheal perflubron (tidal volume of 10 mL/kg and a PEEP of 5 cm H2O). Lung injury was elicited by intravenous administration of Escherichia coliendotoxin. Uninjured animals ventilated as the CMV group served as controls. After 4 hours of mechanical ventilation, the lungs were removed and tissue injury was assessed by light microscopy using a scoring system. RESULTS: Animals in the CMV group had higher lung injury scores in comparison to the PLV group (10+/-4.5 vs. 5+/-3.3, respectively, P < .05). The injury scores were similar for nondependent lung regions (CMV: 8+/-4.3, PLV: 6+/-2.9) but significantly different for the dependent regions (CMV: 12+/-4.6, PLV: 5+/-3.8, P< .05). CONCLUSIONS: PLV is associated with significant attenuation of lung injury, in comparison to CMV. This effect is predominantly due to attenuation of injury in the dependent region of the lung.

Analysis of Variance↗
PubMed1999

Pathophysiology of cardiac extracorporeal membrane oxygenation.

The treatment of cardiogenic shock using inotropic agents and vascular volume expansion places an added burden on the heart. The resultant increase in cardiac work may cause myocardial ischemia and lead to cardiac arrest. Extracorporeal membrane oxygenation (ECMO) may be used to treat cardiogenic shock. It supports systemic circulation, assures diastolic perfusion of the myocardium, and reduces cardiac workload. The rise in blood pressure associated with restoring systemic circulation afterloads the heart and can cause left atrial hypertension and pulmonary edema. ECMO does not automatically reduce cardiac work, especially in the presence of residual shunts. Left atrial drainage or decompression may be essential in certain patients both to avert pulmonary edema and to reduce cardiac work.

Atrial Function, Left↗
PubMed1999

Regional pulmonary blood flow during partial liquid ventilation in normal and acute oleic acid-induced lung-injured piglets.

OBJECTIVE: To determine the spatial distribution of pulmonary blood flow in three groups of piglets: partial liquid ventilation in normal piglets, partial liquid ventilation during acute lung injury, and conventional gas ventilation during acute lung injury. DESIGN: Prospective randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Regional pulmonary blood flow was studied in 21 piglets in the supine position randomized to three different groups: a normal group that received partial liquid ventilation (Normal-PLV) and two acute lung injury groups that received an oleic acid-induced lung injury: partial liquid ventilation during acute lung injury (OA-PLV) and conventional gas ventilation during acute lung injury (OA-Control). Acute lung injury was induced by infusing oleic acid (0.15 mL/kg iv) over 30 mins. Partial liquid ventilation was instituted with perflubron (LiquiVent, 30 mL/kg) after 30 mins in the Normal-PLV and OA-PLV groups. MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and pulmonary mechanics were measured every 15 mins throughout the hour-long study. Pulmonary blood flow was assessed by fluorescent microsphere technique at baseline and after 30, 45, and 60 mins. In the Normal-PLV piglets, pulmonary blood flow decreased from baseline (before injury or partial liquid ventilation) in the most dependent areas of the lung (F ratio = 3.227; p < .001). In the OA-PLV piglets, pulmonary blood flow was preserved over time throughout the lung (F ratio = 1.079; p = .38). In the OA-Control piglets, pulmonary blood flow decreased in the most dependent areas of the lung and increased from baseline in less dependent slices over time (F ratio = 2.48; p = .003). CONCLUSIONS: The spatial distribution of regional pulmonary blood flow is preserved during partial liquid ventilation compared with gas ventilation in oleic acid-induced lung injury.

Animals↗
PubMed1999

The risk of nosocomial pneumonia is not increased during partial liquid ventilation.

OBJECTIVE: To determine whether partial liquid ventilation (PLV) affects the risk of nosocomial pneumonia. STUDY DESIGN: To assess in vitro bacterial adhesion and viability after liquid perfluorocarbon exposure and to assess bacterial recovery after partial liquid ventilation in vivo in rabbits. SETTING: University animal research facility. SUBJECTS: Thirty-six New Zealand White rabbits. INTERVENTIONS: To assess adhesions, radiolabeled Escherichia coli were exposed to perfluorocarbon, incubated against artificial biosurfaces, and compared with nonexposed controls. Bacterial viability in vitro was assessed by exposing broth suspensions of Pasteurella multocida to perflubron for various times. Controls were run in parallel without exposure. Quantitative cultures were performed to determine viability. We undertook short-term and recovery in vivo investigations. The lungs of treated animals were filled with perflubron (approximately 18 mL/kg), and the control rabbits were ventilated without perflubron in an identical fashion. Cryopreserved aliquots of P. multocida were administered via an endotracheal tube. The short-term study animals were ventilated for 6 hrs before being killed. The recovery animals were ventilated for 2-4 hrs, extubated, and killed 20 hrs later. The lungs were removed, aseptically minced, and homogenized. Serial dilutions of the homogenate were quantitatively cultured by manual counting of colonies on agar plates. The recovered organisms were typed for species by the clinical microbiology laboratory. MEASUREMENTS AND MAIN RESULTS: The adhesion of bacteria to immobilized bronchoalveolar lavage and human saliva, respectively, was reduced by 65%+/-7% and 66%+/-1% (p < .05; n = 5) after exposure to perflubron and by 63%+/-9% and 68%+/-6% after exposure to FC-77 (p < .05; n = 5); however, adhesion was not affected by exposure to Rimar. There was no difference in bacterial viability between the control and perflubron-exposed bacteria (n = 5). The in vivo study demonstrated a ten-fold or greater reduction in the number of recovered bacteria in the partial liquid ventilated group compared with the control group. CONCLUSIONS: This study suggests that different perfluorocarbons affect adhesions differently. Perflubron and FC-77 appear to decrease bacterial adhesion, whereas Rimar does not. Rerflubron does not have a direct bactericidal effect. Furthermore, PLV with perflubron decreased the number of viable bacteria per gram of tissue after an intentional inoculation of the airway, suggesting that the risk of nosocomial pneumonia is unlikely to be increased during PLV and may, in fact, be reduced in patients supported with PLV.

Animals↗
PubMed1998

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange.

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.

Animals↗
PubMed1997

Partial liquid ventilation and nitric oxide in congenital diaphragmatic hernia.

PURPOSE: In congenital diaphragmatic hernia (CDH) there is immature lung development with a resulting clinical picture of pulmonary hypoplasia, surfactant deficiency, and pulmonary hypertension. Pulmonary hypoplasia and surfactant deficiency both have been successfully treated using partial liquid ventilation (PLV). Pulmonary hypertension associated with CDH has proven difficult to treat, but inhaled nitric oxide, which is a potent highly selective pulmonary vasodilator, may have potential. The aim of this study was to assess PLV in CDH and to document the effect of nitric oxide when administered through perfluorocarbon. METHODS: This study using the lamb CDH model consisted of two groups; a conventional mechanically ventilated (CMV) group and a PLV group. At 1 and 3 hours, nitric oxide (80 ppm) was given for 15 minutes. Data collected included blood gases, pulmonary function tests, pulmonary and systemic blood pressure. RESULTS: After 30 minutes of ventilation, blood gases in the PLV group were all significantly improved (P < .001): pH, CMV 6.92 +/- 0.15 versus PLV 7.24 +/- 0.11; P(CO2), CMV 139 +/- 26 mmHg versus PLV 52 +/- 11 mmHg; P(O2), CMV 26 +/- 15 mmHg versus PLV 184 +/- 60 mmHg. In addition, there was a significant increase in dynamic compliance and a reduction in pulmonary hypertension. Nitric oxide was only efficacious in the PLV group, causing a further increase in oxygenation and a decrease in pulmonary hypertension. These effects were reversed when the nitric oxide was stopped. CONCLUSION: This study shows that PLV both improves gas exchange and pulmonary mechanics in CDH and allows the effective delivery of nitric oxide to reduce the pulmonary hypertension associated with CDH.

Animals↗
PubMed1996

Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The LiquiVent Study Group.

BACKGROUND: The intratracheal administration of a perfluorocarbon liquid during continuous positive-pressure ventilation (partial liquid ventilation) improves lung function in animals with surfactant deficiency. Whether partial liquid ventilation is effective in the treatment of infants with severe respiratory distress syndrome is not known. METHODS: We studied the efficacy of partial liquid ventilation with perflubron in 13 premature infants with severe respiratory distress syndrome in whom conventional treatment, including surfactant therapy, had failed. Partial liquid ventilation was initiated by instilling perflubron during conventional mechanical ventilation to a volume approximating the functional residual capacity. Infants were considered to have completed the study if they received partial liquid ventilation for at least 24 hours. RESULTS: Ten infants received partial liquid ventilation for 24 to 76 hours. In the other three infants, partial liquid ventilation was discontinued within four hours in favor of high-frequency ventilation, which was not permitted by the protocol, and the data from these infants were excluded from the analysis. Within one hour after the instillation of perflubron, the arterial oxygen tension increased by 138 percent and the dynamic compliance increased by 61 percent; the mean (+/- SD) oxygenation index was reduced from 49 +/- 60 to 17 +/- 16. Chest radiographs showed symmetric filling, with patchy clearing during the return from partial liquid to gas ventilation. There were no adverse events clearly attributable to partial liquid ventilation. Infants were weaned from partial liquid to gas ventilation without complications. Eight infants survived to 36 weeks' corrected gestational age. CONCLUSIONS: Partial liquid ventilation leads to clinical improvement and survival in some infants with severe respiratory distress syndrome who are not predicted to survive.

Fluorocarbons↗
PubMed1996

Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome.

OBJECTIVE: To compare the effectiveness of perfluorocarbon-associated gas exchange to volume controlled positive pressure breathing in supporting gas exchange, lung mechanics, and survival in an acute lung injury model. DESIGN: A prospective, randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Eighteen piglets were randomized to receive perfluorcarbon-associated gas exchange with perflubron (n=10) or volume controlled continuous positive pressure breathing (n=8) after acute lung injury was induced by oleic acid infusion (0.15 mL/kg iv). MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and lung mechanics were measured every 15 mins during a 3-hr study period. All animals developed a metabolic and a respiratory acidosis during the infusion of oleic acid. Following randomization, the volume controlled positive pressure breathing group developed a profound acidosis (p<.05), while pH did not change in the perfluorocarbon-associated gas exchange group. Within 15 mins of initiating perfluorocarbon-associated gas exchange, oxygenation increased from a PaO2 of 52 +/- 12 torr (6.92 +/- 1.60 kPa) to 151 +/- 93 torr (20.0 +/- 12.4 kPa) and continued to improve throughout the study (p<.05). Animals that received volume controlled positive pressure breathing remained hypoxic with no appreciable change in PaO2. Although both groups developed hypercarbia during oleic acid infusion, PaCO2, steadily increased over time in the control group (p<.01). Static lung compliance significantly increased postrandomization (60 mins) in the animals supported by perflurocarbon-associated gas exchange (p<.05), whereas it remained unchanged over time in the volume controlled positive pressure breathing group. However, survival was significantly higher in the perfluorocarbon-associated gas exchange group with eight (80%) of ten animals surviving the entire study period. Only two (25%) of the eight animals in the volume controlled positive pressure breathing group were alive at the end of the study period (log-rank statistic, p=.013). CONCLUSIONS: Perflurocarbon-associated gas exchange enhanced gas exchange, pulmonary mechanics, and survival in this model of acute lung injury.

Animals↗
PubMed1996

Perfluorocarbon-associated gas exchange in normal and acid-injured large sheep.

OBJECTIVES: We hypothesized that a) perfluorocarbon-associated gas exchange could be accomplished in normal large sheep; b) the determinants of gas exchange would be similar during perfluorocarbon-associated gas exchange and conventional gas ventilation; c)in large animals with lung injury, perfluorocarbon-associated gas exchange could be used to enhance gas exchange without adverse effects on hemodynamics; and d) the large animal with lung injury could be supported with an FIO2 of <1.0 during perfluorocarbon-associated gas exchange. DESIGN: Prospective, observational animal study and prospective randomized, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Thirty adult ewes. MEASUREMENT AND MAIN RESULTS: Five normal ewes (61.0 +/- 4.0 kg) underwent perfluorocarbon-associated gas exchange to ascertain the effects of tidal volume, end-inspiratory pressure, and positive end-expiratory pressure (PEEP) on oxygenation. Respiratory rate, tidal volume, and minute ventilation were studied to determine their effects on CO2 clearance. Sheep, weighing 58.9 +/- 8.3 kg, had lung injury induced by instilling 2 mL/kg of 0.05 Normal hydrochloric acid into the trachea. Five minutes after injury, PEEP was increased to 10 cm H2O. Ten minutes after injury, sheep with Pao2 values of <100 torr (<13.3 kPa) were randomized to continue gas ventilation (control, n=9) or to institute perfluorocarbon-associated gas exchange (n=9) by instilling 1.6 L of unoxygenated perflubron into the trachea and resuming gas ventilation. Blood gas and hemodynamic measurements were obtained throughout the 4-hr study. Both tidal volume and end-inspiratory pressure influenced oxygenation in normal sheep during perfluorocarbon-associated gas exchange. Minute ventilation determined CO2 clearance during perfluorocarbon-associated gas exchange in normal sheep. After acid aspiration lung injury, perfluorocarbon-associated gas exchange increased PaO2 and reduced intrapulmonary shunt fraction. Hypoxia and intrapulmonary shunting were unabated after injury in control animals. Hemodynamics were not influenced by the institution of perfluorocarbon-associated gas exchange. CONCLUSIONS: Tidal volume and end-inspiratory pressure directly influence oxygenation during perfluorocarbon-associated gas exchange in large animals. Minute ventilation influences clearance of CO2. In adult sheep with acid aspiration lung injury, perfluorocarbon-associated gas exchange at an FIO2 of <1.0 supports oxygenation and improves intrapulmonary shunting, without adverse hemodynamic effects, when compared with conventional gas ventilation.

Analysis of Variance↗
PubMed1996

Partial liquid ventilation enhances surfactant phospholipid production.

OBJECTIVE: To study the effect of partial liquid ventilation on phospholipid metabolism. DESIGN: Prospective, controlled laboratory study. SETTING: University-affiliated animal research facility. SUBJECTS: Mature New Zealand white rabbits (n = 17). INTERVENTIONS: The rabbits were sedated, anesthetized, and instrumented with tracheostomy and the insertion of an arterial catheter. The rabbits were sequentially assigned to receive conventional mechanical ventilation or partial liquid ventilation with Perflubron (18 mL/kg by bolus fill). Ventilator strategies were identical in both groups and consisted of an FiO2 of 0.5, positive end-expiratory pressure of 4 cm H2O, effective tidal volume of 8 to 13 mL/kg, and rate to maintain Pco2 of 30 to 40 torr (4.0 to 5.3 kPa). Phosphatidylcholine was labeled in vivo by injection of 3H-methylcholine (25 microCi/kg iv). Ventilation was continued for 5.5 hrs. MEASUREMENTS AND MAIN RESULTS: When animals were killed, phosphatidylcholine was extracted from the total lung lavage and from the pulmonary parenchyma. After the separation of phospholipids by thin-layer chromatography, the 3H activity was determined by liquid scintillation counting. Inorganic phosphorus was also determined to assess the enrichment of the phosphatidylcholine. The 3H-phosphatidylcholine activity in the partial liquid ventilation treated- vs. control rabbits demonstrated a 53% increase (p = .051) in the lavage and a 48% increase (p = .013) in the parenchyma for a net 50% (p = .012) total pulmonary increase. The phospholipid content of the partial liquid ventilation treated- vs. the control rabbits demonstrated a 78% increase (p = .046). CONCLUSIONS: We conclude that partial liquid ventilation with Perflubron appears to have no negative impact on phospholipid metabolism but rather enhances surfactant phospholipid synthesis and secretion.

Acute Disease↗
PubMed1995

Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant.

OBJECTIVE: To determine the efficacy of partial liquid ventilation (PLV) by means of a medical-grade perfluorochemical liquid, perflubron (LiquiVent), in premature lambs with respiratory distress syndrome (RDS). Further, to determine the compatibility of perflubron with exogenous surfactant both in vitro and in vivo during PLV. DESIGN: Prospective, randomized, controlled study, with in vitro open comparison. SUBJECTS: Twenty-two premature lambs with RDS. INTERVENTIONS: In vitro assays were conducted on three exogenous surfactants before and after combination with perflubron. We studied four groups of lambs, which received one of the following treatment strategies: conventional mechanical ventilation (CMV); surfactant (Exosurf) plus CMV; PLV; or surfactant plus PLV. MEASUREMENTS AND MAIN RESULTS: In vitro surface tension, measured for three exogenous surfactants, was unchanged in each animal after exposure to perflubron. Lung mechanics and arterial blood gases were serially measured. All animals treated with PLV survived the 5 hours of experiment without complication; several animals treated with CMV died. During CMV, all animals had marked hypoxemia and hypercapnia. During PLV, arterial oxygen tension increased sixfold to sevenfold within minutes of initiation, and this increase was sustained; arterial carbon dioxide tension decreased to within the normal range. Compliance increased fourfold to fivefold during PLV compared with CMV. Tidal volumes were increased during PLV, with lower mean airway pressure. Resistance was similar for both CMV and PLV; there was no difference with surfactant treatment. CONCLUSIONS: We conclude that PLV with perflubron improves lung mechanics and gas exchange in premature lambs with RDS, that PLV is compatible with exogenous surfactant therapy, and that, as a treatment for RDS in this model, PLV is superior to the surfactant studied.

Animals↗
PubMed1995

Cardiorespiratory effects of perfluorocarbon-associated gas exchange at reduced oxygen concentrations.

OBJECTIVE: To determine whether reducing FIO2 during perfluorocarbon-associated gas exchange would cause deterioration of hemodynamics, lung mechanics, or gas exchange in normal piglets. DESIGN: A prospective, controlled animal trial. SETTING: Experimental animal laboratory in a university setting. SUBJECTS: Twelve normal, anesthetized piglets, 7 to 14 days old, and weighing 3.31 +/- 0.75 kg. INTERVENTIONS: After the induction of anesthesia, tracheostomy and catheterization, piglets were stabilized. They were mechanically ventilated with a tidal volume of 15 mL/kg, inspiratory time of 25%, positive end-expiratory pressure of 4 cm H2O, and a respiratory rate of 20 to 28 breaths/min to obtain a baseline PaCO2 between 34 and 45 torr (4.7 and 6.0 kPa). Each animal was studied during continuous positive-pressure breathing, and during perfluorocarbon-associated gas exchange. They were ventilated at an FIO2 of 1.0 for 15 mins. FIO2 was randomly varied among 0.75, 0.5, and 0.3 every 15 mins, then returned to 1.0. At each FIO2, measurements of gas exchange, lung mechanics, and hemodynamics were made. After continuous positive-pressure breathing, perfluorocarbon-associated gas exchange was instituted by replacing the gaseous functional residual capacity of the lungs with perfluorooctylbromide. Animals were then ventilated and measurements were taken. MEASUREMENTS AND MAIN RESULTS: At each FIO2, measurements of gas exchange (arterial blood gases and saturation), lung mechanics (mean airway pressure, static end-inspiratory pressure, and peak inspiratory pressure), and hemodynamics (heart rate, and mean arterial, right atrial, pulmonary artery occlusion, and pulmonary arterial pressures) were recorded. In six piglets, cardiac output was measured at each FIO2 by thermodilution. Cardiac index, indexed oxygen delivery and consumption, and indexed pulmonary vascular resistance were derived using standard formulas. Piglets were well saturated at all FIO2 settings during continuous positive-pressure breathing. However, during perfluorocarbon-associated gas exchange, arterial saturation decreased to 72% at an FIO2 of 0.3. Cardiac index and oxygen consumption were not affected by reducing FIO2 during perfluorocarbon-associated gas exchange, and were not significantly different than during continuous positive-pressure breathing. Oxygen delivery was reduced at an FIO2 of 0.3 during perfluorocarbon-associated gas exchange, but oxygen consumption remained in the flow independent portion of the curve despite arterial desaturation. Pulmonary arterial pressure was higher during perfluorocarbon-associated gas exchange than during continuous positive-pressure breathing. Pulmonary arterial pressure and indexed pulmonary vascular resistance were significantly higher during perfluorocarbon-associated gas exchange at an FIO2 of 0.3 than at any other FIO2 settings. CONCLUSIONS: Piglets showed no adverse effects on lung mechanics during perfluorocarbon-associated gas exchange. Hemodynamics were well supported at all FIO2 settings, and arterial blood was fully oxygenated during perfluorocarbon-associated gas exchange at an FIO2 of > or = 0.5.

Animals↗
PubMed1995

Prolonged studies of perfluorocarbon associated gas exchange and of the resumption of conventional mechanical ventilation.

OBJECTIVE: To determine whether oxygenation and lung mechanics are preserved during perfluorocarbon associated gas exchange of 24 hrs duration and after evaporation of perfluorocarbon. DESIGN: Prospective, experimental animal trials. SETTING: Animal laboratory in a university setting. SUBJECTS: Ten normal, neonatal piglets weighing 2.5 to 4.5 kg. INTERVENTIONS: Ten piglets were anesthetized with fentanyl (25 micrograms/kg/hr), paralyzed with metocurine iodide (0.3 mg/kg) and placed on volume regulated continuous positive pressure breathing instituted at an FIO2 setting of 1.0, tidal volume of 15 mL/kg, respiratory rate of 25 breaths/min and positive end-expiratory pressure of 4 cm H2O. Perfluorocarbon associated gas exchange was initiated by intratracheal instillation of perflouorooctylbromide (30 mL/kg) followed by gas ventilation at the same settings. Evaporative losses were replaced by intratracheal instillation of 2.5 mL/kg/hr of perfluorocarbon. In one group of five piglets, evaporative losses were replaced for 24 hrs until the end of the study. In the other group of five piglets, replacement of perfluorocarbon was discontinued after 2 hrs, although gas ventilation was continued for 24 hrs. Blood gases and lung mechanics were measured in both groups. Histologic evaluation of lungs from both groups of animals was performed. MEASUREMENTS AND MAIN RESULTS: Airway pressures and blood gases were stable throughout the 24-hr study period in both groups. Airway pressures in the evaporative group increased as evaporation of perfluorocarbon neared completion. There was no hemodynamic deterioration during the 24-hr study period. Histology showed good preservation of lung architecture in both groups. CONCLUSIONS: Perfluorocarbon associated gas exchange was safe and effective in normal piglets for a period of 24 hrs. Evaporation of perfluorocarbon and resumption of continuous positive pressure breathing was well tolerated.

Animals↗