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Ronald B Hirschl - One of the best experts on this subject based on the ideXlab platform.

  • Liquid Ventilation in an Infant With Pulmonary Alveolar Proteinosis
    2016
    Co-Authors: Wan Chong Tsai, Dorothy Lewis, Samya Z. Nasr, Ronald B Hirschl
    Abstract:

    Summary. Partial liquid ventilation (PLV) has been applied in various pulmonary diseases. We describe the use of partial liquid ventilation as a lavage method following normal saline (NS) lavage in an infant with pulmonary alveolar proteinosis (PAP) and severe hypoxemia. A 6 weeks old 3.4 kg former 36 weeks gestation boy on supplemental oxygen was transferred to our NICU with persistent tachypnea, dry cough, and increasing oxygen requirements. A lingular open lung biopsy revealed PAP. He developed progressive respiratory failure requiring ventilatory support, necessitating conventional NS lavage, followed by lung lavage with Perflubron (LiquiVent; Alli-ance Pharmaceutical Corp. and Hoechst Marion Roussel) while on venovenous extracorporeal life support (ECLS). Lung lavage with NS and Perflubron yielded minimal cloudy effluent. Gas exchange and pulmonary function deteriorated following NS lavage and attempts to discontinue ECLS were poorly tolerated. In contrast, tidal volume, PaO2, and pulmonary compliance in-creased after PLV, while the (A-a) DO2 decreased to a point where ECLS was no longer required. Once Perflubron was added repeatedly to the ventilator circuit to correct for evaporation over the 4 days of PLV. Cardiovascular status remained stable for several days; however, eventually he required reinitiation of ECLS and more mechanical ventilatory support with each trial off ECLS. He was maintained on high pressures and FiO2 without any possibility to wean him from me-chanical ventilation. Life support was withdrawn 1 month after admission. The survival from PAP in infants remains dismal, even with total lung NS lavage. While both NS and Perflubron lavage in this patient were not effective in removing the proteinaceous alveolar debris, PLV following NS lavage was associated with an improvement in gas exchange and lung compliance. Pediat

  • effect of Perflubron induced lung growth on pulmonary vascular remodeling in congenital diaphragmatic hernia
    Pediatric Surgery International, 2016
    Co-Authors: Mansi Shah, Ronald B Hirschl, Michael R Phillips, Benjamin S Bryner, George B Mychaliska, S Mclean
    Abstract:

    Congenital diaphragmatic hernia (CDH) involves lung hypoplasia and pulmonary hypertension (PH). Post-natal Perflubron ventilation induces lung growth. This phenomenon is called Perflubon-induced lung growth (PILG). However, it does not appear to ameliorate PH in CDH. We aim to determine the effect of PILG on pulmonary vascular remodeling in neonates with CDH and PH requiring extracorporeal membrane oxygenation (ECMO). Lung tissue from four patients was obtained, three treated with PILG + ECMO, and one maintained on conventional ventilation + ECMO (control). The distribution of collagen was assessed with Masson’s trichrome stain. Immunohistochemistry was done to assess cell proliferation and immunofluorescence to assess vascular morphology. Comparing PILG vs. control, there was an increase in vessel wall diameter (6.85 μm, 10.28 μm, and 10.35 μm vs. 4.34 μm), increase in collagen thickness in two PILG patients (35.66 μm, 14.23 μm, and 38.46 μm vs. 22.16 μm), and decrease in lumen diameter despite similar total area (48.99 μm, 41.74 μm, and 36.32 μm vs. 51.56 μm) for each PILG patient vs. the control patient, respectively. PILG does not appear to improve pulmonary vascular remodeling that occurs with PH. The findings are descriptive and will require larger samples to validate the significance of the findings. Overall, further studies will be required to identify the mechanistic causes of PH in CDH to create effective treatments.

  • safety and efficacy of Perflubron induced lung growth in neonates with congenital diaphragmatic hernia results of a prospective randomized trial
    Journal of Pediatric Surgery, 2015
    Co-Authors: George B Mychaliska, Benjamin S Bryner, Ronald E Dechert, Jeannie Kreutzman, Mike Becker, Ronald B Hirschl
    Abstract:

    Abstract Background Mechanical transduction has been shown to promote fetal lung growth. We examined the safety and efficacy of Perflubron-induced lung growth (PILG) in neonates with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO). Methods Infants with left-sided CDH requiring ECMO were eligible. Exclusion criteria included active air leak, intracranial hemorrhage, major congenital anomalies, and oxygenation index >25 for 24hours. Perflubron was instilled endotracheally and continuous positive airway pressure was applied without ventilation. Survival to discharge was the primary outcome. Daily chest radiographs were used to quantify lung size (the secondary outcome). Midway through the study our institutional practice shifted toward earlier repair of CDH. Results Eight infants were randomized to each arm. In the conventional-ventilation arm, six survived to discharge (75%). In the Perflubron arm, four survived (50%); the others succumbed to suprasystemic pulmonary hypertension. No adverse events related to Perflubron occurred. Within the Perflubron group, 4/8 patients had "late repair" (15–19days of life [DOL]) and 4 had "early repair" (2–3 DOL). "Early repair" patients had similar total lung growth, but accelerated growth and shorter ECMO runs. Conclusion PILG is safe in CDH and doubles the total lung size on average (accelerated with early repair). Despite amelioration of pulmonary hypoplasia with PILG, pulmonary hypertension persists.

  • end expiratory lung volumes and density distribution patterns during partial liquid ventilation in healthy and oleic acid injured sheep a computed tomography study
    Critical Care Medicine, 2003
    Co-Authors: Thomas Luecke, Ronald B Hirschl, Juergen P Meinhardt, Peter Herrmann, Sascha Klemm, Andreas Weiss, Gerald Weisser, Michael Quintel
    Abstract:

    OBJECTIVE: To determine end-expiratory lung volumes (EELVs) and the distribution of gas and Perflubron during low- and high-dose partial liquid ventilation (PLV) in healthy and oleic-acid-injured lungs. DESIGN: A prospective, randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Adult sheep. INTERVENTIONS: A total of 18 sheep were randomly divided into two groups (healthy and oleic acid lung injury) and received PLV with Perflubron at incremental doses. MEASUREMENTS AND MAIN RESULTS: Animals were ventilated in a volume-control mode with a positive end-expiratory pressure of 5 cm H2O. Baseline computed tomographic scans of the entire lung were obtained during end-expiratory hold. Thereafter, the animals were randomized to undergo either PLV alone (healthy group) or after oleic acid lung injury was introduced (injury group). In both groups, PLV was induced by instilling 10 mL/kg Perflubron into the endotracheal tube over 5 mins (low-dose PLV). At 60 mins after dosing, another set of computed tomographic scans during end-expiratory hold was obtained. Thereafter, another 20 mL/kg Perflubron was instilled in both groups (cumulative dose, 30 mL/kg Perflubron, high-dose PLV), and computed tomographic scanning was repeated 60 mins later. EELVs were calculated. To study density distribution patterns, the lungs were divided into nine segments, and the mean Hounsfield attenuation number was calculated for each segment. In healthy animals, low-dose PLV did not change EELV (47.5 +/- 8.1 mL/kg vs. 44.5 +/- 6.1 mL/kg at 10 mL/kg Perflubron), whereas high-dose PLV significantly increased EELV (58.1 +/- 3.3 mL/kg, p <.01). Oleic acid lung injury significantly reduced EELV (53.9 +/- 7.5 mL/kg vs. 43.9 +/- 8.7 mL/kg, p <.01). Low-dose PLV reestablished baseline EELV (59.8 +/- 10.5 mL/kg), and high-dose PLV resulted in a significant increase in EELV (89.2 +/- 12 mL/kg, p =.003). PLV increased the mean Hounsfield attenuation number along the ventrodorsal axis in the three coronal blocks in a dose-dependent manner. In the oleic acid lung injury group, PLV produced a more homogeneous pattern of density distribution, with the highest Hounsfield attenuation numbers observed in the medial segments. CONCLUSION: High-dose PLV significantly increased EELV in both states, indicating lung distention. Healthy lungs were filled in a dose-dependent, gravity-governed fashion, showing steep craniocaudal and ventrodorsal gradients. In the oleic acid lung injury model studied, Perflubron tended to accumulate on top of the most severely injured dorsal and diaphragmatic parts, rendering effective recruitment by liquid positive end-expiratory pressure in these regions questionable.

  • exposure to Perflubron is associated with decreased syk phosphorylation in human neutrophils
    Journal of Applied Physiology, 2001
    Co-Authors: Rosemarie Fernandez, Ronald B Hirschl, Vidya Sarma, Ellen M Younkin, Peter A Ward, John G Younger
    Abstract:

    Liquid ventilation with Perflubron is associated with reduced neutrophil recruitment into the lung during acute injury. Perflubron also reduces chemotactic responses, the respiratory burst, and cytokine production in neutrophils and in alveolar macrophages in vitro. In the current studies, the effect of Perflubron on neutrophil chemotaxis to formyl-Met-Leu-Phe (fMLP) and phagocytosis of opsonized sheep erythrocytes (EA) correlated with decreased phosphorylation of Syk, an important intracellular second messenger in pathways regulating neutrophil functional responses. Brief (5 min) exposure of neutrophils to Perflubron resulted in a dose-dependent reduction in chemotaxis to fMLP and reduced phagocytosis of EA but no apparent morphological changes as seen by electron microscopy. Concurrently, there was a reduction in both total cytosolic tyrosine phosphorylation and Syk phosphorylation. Binding studies indicated that this effect was neither a result of impaired ligand-receptor affinity nor a change in the number of fMLP receptors available on the neutrophil surface. These results suggest that Perflubron nonspecifically affects cellular activation as measured by tyrosine phosphorylation perhaps by interfering with transmembrane signal transduction.

Thomas H Shaffer - One of the best experts on this subject based on the ideXlab platform.

  • hyperoxia induced changes in human airway epithelial cells the protective effect of Perflubron
    Pediatric Critical Care Medicine, 2005
    Co-Authors: Polani Ramesh B Babu, Aaron Chidekel, Thomas H Shaffer
    Abstract:

    Objective:To determine the protective effect of Perflubron (PFB), a type of perfluorochemical liquid, in hyperoxia-induced cellular injury in the human airway epithelial cells.Design:A controlled, in vitro laboratory study.Setting:Tertiary-care children’s hospital.Subjects:Human airway epithelial ce

  • perfluorochemical rescue after surfactant treatment effect of Perflubron dose and ventilatory frequency
    Journal of Applied Physiology, 1998
    Co-Authors: Marla R Wolfson, Nancy E Kechner, Robert Roache, Jeanpierre Dechadarevian, Helena E Friss, David S Rubenstein, Thomas H Shaffer
    Abstract:

    To test the hypotheses that perfluorochemical (PFC) liquid rescue after natural surfactant (SF) treatment would improve pulmonary function and histology and that this profile would be influenced by PFC dose or ventilator strategy, anesthetized preterm lambs (n = 31) with respiratory distress were studied using nonpreoxygenated Perflubron. All animals received SF at 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventional mechanical gas ventilation (n = 8), 2) 30 ml/kg Perflubron with gas ventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8), 3) 10 ml/kg Perflubron with PLV at 60 breaths/min (n = 7), and 4) 10 ml/kg Perflubron with PLV at 30 breaths/min (n = 8). All animals tolerated instillation without additional cardiopulmonary instability. All Perflubron-rescued groups demonstrated sustained improvement in gas exchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement was directly related to Perflubron dose and breathing frequency; peak inspiratory pressure required to achieve physiological gas exchange was lower in the higher-dose and -frequency groups, and mean airway pressure was lower in the lower-frequency group. Lung expansion was greater and evidence of barotrauma was less in the higher-dose and -frequency group; regional differences in expansion were not different as a function of dose but were greater in the lower-frequency group. Regional differences in lung Perflubron content were reduced in the higher-dose and -frequency groups and greatest in the lower-dose and -frequency group. The results suggest that, whereas PLV of the SF-treated lung improves gas exchange and lung mechanics, the protective benefits of Perflubron in the lung may depend on dose and ventilator strategy to optimize PFC distribution and minimize exposure of the alveolar-capillary membrane to a gas-liquid interface.

  • virtual bronchoscopy with Perflubron enhancement dagger 1814
    Pediatric Research, 1997
    Co-Authors: Bart Milestone, Marla R Wolfson, Thomas F Miller, Robert G Stern, Thomas H Shaffer
    Abstract:

    The advent of helical computerized tomography (CT) has allowed for volumetric data acquisition with markedly improved multiplanar reconstruction as well as three dimensional rendering. Post-processing software has permitted changing the viewer frame of reference thus allowing direct visualization of the inside of large airways or so called virtual bronchoscopy. Air within the lumen supplies contrast; however, in bronchial tree branches, the walls are thin thereby reducing contrast and resolution. We hypothesized that the instillation of a dose of liquid Perflubron (LiquiVent®, Alliance Pharm Corp, San Diego, CA) would increase airway contrast and therefore increase airway resolution. To test this hypothesis, we compared helical CT images in an anesthetized, intubated, adolescent New Zealand rabbit model during mechanical gas ventilation at end inspiration and expiration. Imaging was performed without and with 15 ml/kg of Perflubron in the lungs. A Picker PQ 5000 helical CT scanner was used and targeted 10 cm FOV, 3mm slice thickness, with a pitch of 1.25, images reconstructed every 3mm with a smooth spatial reconstruction algorithm, and mA/kVp of 200/120. The bronchoscopic CT without Perflubron only allowed visualization of the first 2 generations with poor resolution of 3rd order branches and beyond. In contrast, images with Perflubron permitted improved resolution of the tracheobronchial tree to the 5th order branches. These preliminary studies demonstrate that Perflubron liquid in the lungs can enhance bronchoscopic CT images of the tracheobronchial tree by improving contrast and resolution of more distal generations of airways. This new innovation represents a potentially favorable combination of perfluorochemicals as contrast medium with the emerging technology of virtual bronchoscopy. (Perflubron provided by Alliance Pharm Corp & Hoechst Marion Roussel)

  • partial liquid ventilation with Perflubron in premature infants with severe respiratory distress syndrome
    The New England Journal of Medicine, 1996
    Co-Authors: Corinne L Leach, Marla R Wolfson, David S Rubenstein, Thomas H Shaffer, Jay S Greenspan, Craig J Jackson, Robert A Delemos, Bradley P Fuhrman
    Abstract:

    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 fa...

  • developmental differences in Perflubron uptake into the blood during tidal liquid ventilation tlv in the immature lamb 1310
    Pediatric Research, 1996
    Co-Authors: Nancy E Kechner, Robert Roache, Thomas F Miller, Cynthia Cox, Raymond Foust, Maria R Wolfson, Thomas H Shaffer
    Abstract:

    Tidal liquid ventilation (TLV) with perfluorochemical liquids (PFC) has been shown to provide effective gas exchange in term and preterm lambs with respiratory failure. PFCs have very low surface tensions and have high respiratory gas solubilities. It is these physical characteristics that make PFC an ideal media with which to support gas exchange in the stiff, noncompliant lungs characteristic of Infant Respiratory Distress Syndrome(IRDS). Although PFC is bioinert, nontoxic, and nonbiotransformable, a small quantity does cross into the blood. To determine if there is a developmental difference in PFC uptake in an animal model which resembles the cardiopulmonary development of human neonates currently receiving PFC therapy, 2 groups of premature lambs [Gr 1: 111 ±.23 days; n=6) and Gr 2: 123±.95 days; n=6)] were delivered by caesarean section, anesthetized, paralyzed, tracheotomized, placed on a time-cycled, pressure-limited tidal liquid ventilator, and ventilated with Perflubron (Liquivent®: Alliance Pharm. Corp.) for 4 hours. Ventilation was modulated to maintain physiologic blood gases. Blood PFC content was determined by headspace analysis using an electron capture detector gas chromatograph on samples taken in utero, every 15 mins up to 1 hour, and every 30 mins to 4 hrs. These data were compared to that of previously evaluated term lambs (Pediatr Res (37): A1414). Results in μgm/gm (mean ± SE) are presented below:Table These data demonstrate that very minute (all values < 10μgm/gm) but different (*p<.01) quantities cross into the blood of the immature lamb following tidal liquid ventilation. The mean over 4 hrs for Gr 1, Gr 2, and the term lambs were 4.31 ±.29, 6.97±.36, and 7.35 ±.36, respectively, showing comparable levels in term and preterm blood Perflubron content. These data suggest that even in the presence of high lung permeability of prematurity, Perflubron blood content does not exceed that of a normal, term newborn lamb.(Supp by AlliancePharm Corp,R29HD26341)

Beverly A Teicher - One of the best experts on this subject based on the ideXlab platform.

  • influence of an anti angiogenic treatment on 9l gliosarcoma oxygenation and response to cytotoxic therapy
    International Journal of Cancer, 1995
    Co-Authors: Beverly A Teicher, Norman P Dupuis, Sylvia A. Holden, Gulshan Ara, F Liu, Jia Yuan, Masahiko Ikebe, Yoshihiro Kakeji
    Abstract:

    Tissue oxygen tensions were measured in subcutaneously growing rat 9L gliosarcoma under normal air and carbogen breathing conditions prior to and after i.v. administration of a Perflubron emulsion. When these animals were treated with the anti-angiogenic agents TNP-470 and minocycline for 5 days prior to oxygen measurement, tumor hypoxia was decreased compared with untreated tumors. Hypoxia, defined as the percent of pO2 readings < or = 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the Perflubron emulsion and carbogen breathing. These effects were manifest in the increased response of the tumor to single-dose (10, 20 and 30 Gy) radiation therapy. Twenty-four hours after treatment with BCNU oxygenation of the tumors was not altered; however, 24 hr after administration of adriamycin oxygenation of the tumors was increased such that hypoxia in adriamycin-treated tumors in animals receiving the Perflubron emulsion and carbogen was reduced to 21%. Tumor growth delay in the s.c. tumors was increased by the addition of treatment with the anti-angiogenic agents from day 4 through day 18 post-tumor cell implantation along with BCNU or adriamycin on days 7-11. Administration of the Perflubron emulsion and carbogen breathing resulted in increased tumor growth delay with the chemotherapeutic agents alone and in combination with the anti-angiogenic agents. Life span in animals bearing intracranially implanted 9L gliosarcoma progressively increased with administration of the anti-angiogenic agents and then the anti-angiogenic agents and Perflubron emulsion/carbogen compared to treatment with BCNU or adriamycin.

  • restoration of tumor oxygenation after cytotoxic therapy by a Perflubron emulsion carbogen breathing
    The cancer journal from Scientific American, 1995
    Co-Authors: Beverly A Teicher, Norman P Dupuis, Sylvia A. Holden, Donna A. Goff
    Abstract:

    PURPOSE: Hypoxic cells are presumed to be an obstacle to successful cancer treatment because these cells are protected from the cytotoxic effects of radiotherapy and certain anti-cancer drugs. The current study was conducted to determine the effect of cytotoxic therapy on tumor oxygenation and the effect of administration of a perfluorochemical emulsion/carbogen breathing treatment on tumor oxygenation after cytotoxic therapy. MATERIALS AND METHODS: Female Fisher 344 rats bearing 13762 mammary carcinoma cells implanted subcutaneously in a hindlimb were treated with standard therapeutic single doses of anti-tumor treatments of several types, including alkylating agents (cisplatin, melphalan, cyclophosphamide); natural products (doxorubicin, paclitaxel, etoposide); antimetabolites (fluorouracil); hypoxic cell-selective agents (mitomycin, SR-4233); and fractionated irradiation (3 Gy/day for 5 days). The oxygen levels in the tumors were measured with an Eppendorf PO2 histograph before the treatment and 24 hours after treatment under air breathing and carbogen breathing conditions, and after administration of a Perflubron emulsion under air breathing and carrbogen breathing conditions. Fifty to 60 points were measured per tumor, and 8 to 10 tumors made up each group. RESULTS: The tumors were more hypoxic after treatment with every anticancer treatment. The percentage of PO2 readings < or = 5 mmHg in the untreated tumors was 49% and ranged from 85% (radiotherapy) to 59% (etoposide) in the treated tumors. Administration of the Perflubron emulsion (8 mL/kg) and carbogen breathing (95% O2/5% CO2) increased the oxygenation of the tumors such that the percentage of PO2 readings < or = 5 mmHg was 32% in the untreated control tumors and ranged from 27% (radiotherapy) to 56% (doxorubicin) in the treated tumors. There was a direct correlation between the level of tumor cell killing and the increased oxygenation observed in the tumor. CONCLUSION: Tumors may be more hypoxic after an effective dose of a cytotoxic therapy, and administration of a Perflubron emulsion/carbogen mixture can increase the tumor oxygen content when hypoxia is the result of cytotoxic therapy. Hypoxia produced by therapy may be regarded as a mechanism of resistance that leads to diminished tumor cell killing with subsequent doses of drugs or radiation. The restoration of tumor oxygenation by the Perflubron emulsion/carbogen breathing may provide a clinically relevant means of overcoming at least in part hypoxia-related resistance.

  • restoration of tumor oxygenation after cytotoxic therapy by a Perflubron emulsion carbogen breathing
    The cancer journal from Scientific American, 1995
    Co-Authors: Norman P Dupuis, M. F. Robinson, Krishna Menon, Tadashi Kusumoto, F Liu, Beverly A Teicher
    Abstract:

    Female, Fisher 344 rats bearing 13762 mammary carcinoma implanted subcutaneously in a hind limb were treated with standard therapeutic single doses of antitumor treatments of several types including: 1) antitumor alkylating agents (cisplatin, cyclophosphamide); 2) natural products (adriamycin, taxol and etoposide); 3) antimetabolites (5-flourouracil); 4) hypoxic cell selective agents (mitomycin C, SR-4233) as well as 5) fractionated radiation therapy (3 Gray daily for 5 days). The oxygen levels in the tumors were measured in the absence of treatment and 24 hrs. after treatment using an Eppendorf p02 histograph. Fifty- to sixty-points were measured per tumor and 8-10 tumors comprised each group. The tumors were more hypoxic post treatment with every anticancer drug or radiation. The percent of p02 readings < or = 5 mmHg in the untreated tumors ranged from 85% (x-rays) to 59% (etoposide). Administration of the Perflubron emulsion (8 ml/kg) and carbogen breathing (95% O2/5% CO2) increased the oxygenation of the tumors such that the percent of pO2 readings < or = 5 mmHg was 32% in the untreated controls and ranged from 27% (x-rays) to 56% (adria) in the treated tumors. These results indicate that administration of a Perflubron emulsion/carbogen can increase the oxygen content of tumors when hypoxia is the result of cytotoxic therapy.

  • reduced oxygenation in a rat mammary carcinoma post radiation and reoxygenation with a Perflubron emulsion carbogen breathing
    in Vivo, 1994
    Co-Authors: Beverly A Teicher, Norman P Dupuis, M. F. Robinson, Tadashi Kusumoto, Krishna Menon
    Abstract:

    : Oxygen profiles of the rat mammary 13672 carcinoma were determined using a pO2 histograph prior to treatment and 24 hrs. and 48 hrs. after 2 or 5 fractions of 3 gray given once daily. The tumors were much more hypoxic at 24 hrs. post radiation therapy than prior to therapy. There was little increase in the oxygenation of the tumors at 48 hrs. post therapy compared with 24 hrs. post therapy indicating that reoxygenation was occurring very slowly in this tumor. Carbogen breathing improved the oxygenation of the tumors under each of the conditions studied. Administration of a Perflubron emulsion (8 ml/kg) produced little or no change in the oxygenation of the tumors under normal air breathing conditions. However, with the addition of carbogen breathing to administration of the Perflubron emulsion there was an increase in the mean/median pO2's of the tumors to levels equal to or greater than carbogen breathing alone. Perhaps most significantly administration of the Perflubron emulsion with carbogen breathing increased the oxygenation of the most hypoxic regions of the tumors but carbogen breathing alone did not.

  • reduced oxygenation in a rat mammary carcinoma after chemo or radiation therapy and reoxygenation with Perflubron emulsion carbogen breathing
    Journal of Cancer Research and Clinical Oncology, 1994
    Co-Authors: Beverly A Teicher, Norman P Dupuis, Tadashi Kusumoto, Enrique Alvarez Sotomayor, Krishna Menon
    Abstract:

    Rat 13672 mammary carcinoma tumors were grown subcutaneously in the hind legs of female Fischer 344 rats to a volume of about 1 cm3. Tumor oxygenation was measured using an EppendorfPO2 histograph. Tumor oxygen measurements were made under four conditions: (a) normal air breathing, (b) carbogen breathing, (c) after intravenous administration of a Perflubron emulsion (8 ml/kg) with air breathing and (d) after intravenous administration of a Perflubron emulsion (8 ml/kg) with carbogen breathing. Tumor oxygenation was examined without treatment or 24 h and 48 h after treatment with cyclophosphamide (300 mg/kg, i.p.) or cisplatin (8 mg/kg, i.p.] or after the fifth dose of a daily regimen of 3-Gy irradiation (5×3 Gy). Under normal air-breathing conditions 49% of the tumor had aPO2≤670 Pa (5 mm Hg). The degree of hypoxia in the tumors increased after each treatment such that 24 h after treatment 65%–85% of the oxygen readings were ≤670 Pa and 48 h after treatment 60%–74% of the oxygen readings were ≤670 Pa. Administration of the Perflubron emulsion/carbogen atmosphere increased the oxygen content of the tumors both without treatment and after each of the treatments. A knowledge of tumor oxygen content over the course of treatment and the ability to increase tumor oxygen should allow for the development of more rational treatment combinations and better treatment outcomes.

Marla R Wolfson - One of the best experts on this subject based on the ideXlab platform.

  • Perfluorochemical rescue after surfactant treatment: effect of Perflubron dose and ventilatory frequency
    2016
    Co-Authors: Marla R Wolfson, Nancy E Kechner, Robert Roache, David S Rubenstein, H. Shaffer, Marla R, Robert F
    Abstract:

    chemical rescue after surfactant treatment: effect of perflu-bron dose and ventilatory frequency. J. Appl. Physiol. 84(2): 624–640, 1998.—To test the hypotheses that perfluorochemi-cal (PFC) liquid rescue after natural surfactant (SF) treat-ment would improve pulmonary function and histology and that this profile would be influenced by PFC dose or ventilator strategy, anesthetized preterm lambs (n 5 31) with respira-tory distress were studied using nonpreoxygenated perflu-bron. All animals received SF at 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conven-tional mechanical gas ventilation (n 5 8), 2) 30 ml/kg Perflubron with gas ventilation [partial liquid ventilatio

  • perfluorochemical rescue after surfactant treatment effect of Perflubron dose and ventilatory frequency
    Journal of Applied Physiology, 1998
    Co-Authors: Marla R Wolfson, Nancy E Kechner, Robert Roache, Jeanpierre Dechadarevian, Helena E Friss, David S Rubenstein, Thomas H Shaffer
    Abstract:

    To test the hypotheses that perfluorochemical (PFC) liquid rescue after natural surfactant (SF) treatment would improve pulmonary function and histology and that this profile would be influenced by PFC dose or ventilator strategy, anesthetized preterm lambs (n = 31) with respiratory distress were studied using nonpreoxygenated Perflubron. All animals received SF at 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventional mechanical gas ventilation (n = 8), 2) 30 ml/kg Perflubron with gas ventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8), 3) 10 ml/kg Perflubron with PLV at 60 breaths/min (n = 7), and 4) 10 ml/kg Perflubron with PLV at 30 breaths/min (n = 8). All animals tolerated instillation without additional cardiopulmonary instability. All Perflubron-rescued groups demonstrated sustained improvement in gas exchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement was directly related to Perflubron dose and breathing frequency; peak inspiratory pressure required to achieve physiological gas exchange was lower in the higher-dose and -frequency groups, and mean airway pressure was lower in the lower-frequency group. Lung expansion was greater and evidence of barotrauma was less in the higher-dose and -frequency group; regional differences in expansion were not different as a function of dose but were greater in the lower-frequency group. Regional differences in lung Perflubron content were reduced in the higher-dose and -frequency groups and greatest in the lower-dose and -frequency group. The results suggest that, whereas PLV of the SF-treated lung improves gas exchange and lung mechanics, the protective benefits of Perflubron in the lung may depend on dose and ventilator strategy to optimize PFC distribution and minimize exposure of the alveolar-capillary membrane to a gas-liquid interface.

  • virtual bronchoscopy with Perflubron enhancement dagger 1814
    Pediatric Research, 1997
    Co-Authors: Bart Milestone, Marla R Wolfson, Thomas F Miller, Robert G Stern, Thomas H Shaffer
    Abstract:

    The advent of helical computerized tomography (CT) has allowed for volumetric data acquisition with markedly improved multiplanar reconstruction as well as three dimensional rendering. Post-processing software has permitted changing the viewer frame of reference thus allowing direct visualization of the inside of large airways or so called virtual bronchoscopy. Air within the lumen supplies contrast; however, in bronchial tree branches, the walls are thin thereby reducing contrast and resolution. We hypothesized that the instillation of a dose of liquid Perflubron (LiquiVent®, Alliance Pharm Corp, San Diego, CA) would increase airway contrast and therefore increase airway resolution. To test this hypothesis, we compared helical CT images in an anesthetized, intubated, adolescent New Zealand rabbit model during mechanical gas ventilation at end inspiration and expiration. Imaging was performed without and with 15 ml/kg of Perflubron in the lungs. A Picker PQ 5000 helical CT scanner was used and targeted 10 cm FOV, 3mm slice thickness, with a pitch of 1.25, images reconstructed every 3mm with a smooth spatial reconstruction algorithm, and mA/kVp of 200/120. The bronchoscopic CT without Perflubron only allowed visualization of the first 2 generations with poor resolution of 3rd order branches and beyond. In contrast, images with Perflubron permitted improved resolution of the tracheobronchial tree to the 5th order branches. These preliminary studies demonstrate that Perflubron liquid in the lungs can enhance bronchoscopic CT images of the tracheobronchial tree by improving contrast and resolution of more distal generations of airways. This new innovation represents a potentially favorable combination of perfluorochemicals as contrast medium with the emerging technology of virtual bronchoscopy. (Perflubron provided by Alliance Pharm Corp & Hoechst Marion Roussel)

  • partial liquid ventilation with Perflubron in premature infants with severe respiratory distress syndrome
    The New England Journal of Medicine, 1996
    Co-Authors: Corinne L Leach, Marla R Wolfson, David S Rubenstein, Thomas H Shaffer, Jay S Greenspan, Craig J Jackson, Robert A Delemos, Bradley P Fuhrman
    Abstract:

    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 fa...

  • use of liquid ventilation with Perflubron during extracorporeal membrane oxygenation chest radiographic appearances
    Radiology, 1995
    Co-Authors: George W Gross, Marla R Wolfson, John S Greenspan, William W Fox, S D Rubenstein, Thomas H Shaffer
    Abstract:

    PURPOSE: To assess the effectiveness of performing liquid ventilation with Perflubron in neonates with severe respiratory failure or pulmonary hypertension who receive extracorporeal membrane oxygenation (ECMO) life support. MATERIALS AND METHODS: We studied an infant (aged 1 month) and a neonate with respiratory failure who underwent ECMO and liquid ventilation with Perflubron, which was slowly instilled via an endotracheal tube (in the infant, 40 mL for more than 1 hour; in the neonate, 28 mL within 1 hour). RESULTS: The infant survived termination of ECMO support and has been breathing room air since 6 months of age. The neonate died soon after ECMO support was withdrawn. CONCLUSION: A minority of neonates or infants with severe respiratory failure or pulmonary hypertension do not respond adequately to treatment with ECMO and are almost certain to die with termination of ECMO support. Liquid ventilation with Perflubron offers a potential salvage therapy in this patient population. In addition, perflubr...

Edward A Norfleet - One of the best experts on this subject based on the ideXlab platform.

  • selective aortic arch perfusion using serial infusions of Perflubron emulsion
    Academic Emergency Medicine, 1997
    Co-Authors: James E Manning, Charles A Murphy, Sebastian G Perretta, D N Batson, T W Gansman, Edward A Norfleet
    Abstract:

    Objective: To determine whether selective aortic arch perfusion (SAAP) using serial infusions of oxygenated Perflubron emulsion combined with aortic epinephrine (AoE) administration is more effective than conventional therapy in treating cardiac arrest. Methods: An experimental cardiac arrest model (10 min ventricular fibrillation and 2 min CPR) was used with 12 mixed-breed canines, randomized into 2 groups: control (n = 6), CPR and IV epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min; or AoE-SAAP (n = 6), CPR and aortic epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min, and serial SAAP with oxygenated 60% weightholume (w/v) Perflubron emulsion as follows: 300 mL over 30 sec at 12 rnin as continuous SAAP without CPR; 150 mL over 20–30 sec at 15 min and 18 rnin as pulsed diastolic SAAP during CPR. Results: AoE-SAAP resulted in increased coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) compared with control. CPR-diastolic (release phase) CPP during pulsed diastolic SAAP was similar to or greater in magnitude than the CPP generated during the initial SAAP infusion without CPR. ROSC for control was 0/6 and for AoE-SAAP was 416 (p 60 mm Hg was 8.0 ± 1.2 rnin in the 4 resuscitated AoE-SAAP animals. Conclusion: The combination of AoE with SAAP infusions of oxygenated Perflubron emulsion was more effective than conventional resuscitation therapy. Pulsed diastolic SAAP is a promising method for performing SAAP.

  • selective aortic arch perfusion during cardiac arrest enhanced resuscitation using oxygenated Perflubron emulsion with and without aortic arch epinephrine
    Annals of Emergency Medicine, 1997
    Co-Authors: James E Manning, Neil D Batson, Frederick B Payne, Nazir Adam, Charles A Murphy, Sebastian G Perretta, Edward A Norfleet
    Abstract:

    Abstract Study objective: To evaluate selective aortic arch perfusion (SAAP) with an oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during cardiac arrest. Methods: This randomized, controlled study, undertaken at a university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes. Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE) in the same fashion as the control group but were also subjected to SAAP with 275 mL of oxygenated 60% wt/vol Perflubron emulsion over 30 seconds. Group 3 dogs (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the first epinephrine dose was given intraaortically. Results: Coronary perfusion pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly greater in the AoE-SAAP group than in the control group. Return of spontaneous circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1±1.9 minutes in the AoE-SAAP group, compared with 11.0±5.8 minutes in the IVE-SAAP group. Conclusion: SAAP with oxygenated Perflubron emulsion improved ROSC, both with and without aortic arch epinephrine. The combination of SAAP with Perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more rapid ROSC. [Manning JE, Batson DN, Payne FB, Adam N, Murphy CA, Perretta SG, Norfleet EA: Selective aortic arch perfusion during cardiac arrest: Enhanced resuscitation using oxygenated Perflubron emulsion, with and without aortic arch perfusion. Ann Emerg Med May 1997; 29:580-587.]