INTERFACIAL MECHANICS IN INTRAVASCULAR GAS EMBOLISM

Summary

Principal Investigator: David Eckmann
Affiliation: University of Pennsylvania
Country: USA
Abstract: Vital organ blood flow can be compromised by microvascular gas embolism that occurs during surgery, endoscopic procedures, and in decompression sickness. The associated morbidity and mortality carry considerable human and economic impact. The pathophysiology of gas lesion disease has been studied little and is poorly understood. The initiating events involve bubble lodging within the vasculature. The molecular mechanical basis of bubble adhesion to the vessel wall causing blood flow obstruction is unknown. Our preliminary experiments suggest that blood flow obstruction is caused by adhesion of the bubble surface to the endothelial glycocalyx. Our global hypothesis is that surface-surface adhesion interactions between the endothelial glycocalyx and the bubble interface control bubble lodging, and thus determine microcirculatory blood flow and resultant organ injury. We will test this hypothesis via four Specific Aims. To identify determinants of bubble adhesion to the vessel wall, we will use in vivo and in vitro methods and biomimetic glycocalyx constructs. Once the molecular basis of adhesion is identified, we predict that modulation of adhesion by administration of (1) surfactants (a polydimethylsiloxane, a nonionic polyol, and a perfluorocarbon) targeted to bubble-blood interfaces and (2) compounds that modify the endothelial surface layer (air stripping, degradation by Ox-LDL and Heparinase), will alter obstruction of blood flow and development of injury in embolized tissue and organs. Experimental methods will include neurobehavioral assessment, brain microdialysis, histopathology, and transcript profiling in a rat model of middle cerebral artery gas embolism, intravital microscopy in rat cremaster muscle, and measurement of bubble adhesion force in excised microvessels and in microcapillary tubes lined with synthetic endothelial surface layers. The use of preclinical novel pharmacological interventions in the proposed research will enable identification of potential therapeutic targets to reduce bubble adhesion and treat gas embolism. The only clinical alternative is hyperbaric therapy, which requires patient transport to a chamber for postembolism treatment, and is therefore generally used only in catastrophic cases.
Funding Period: 1998-12-01 - 2008-02-29
more information: NIH RePORT

Top Publications

  1. pmc Chemically grafted fibronectin for use in QCM-D cell studies
    Judith Kandel
    Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biosens Bioelectron 58:249-57. 2014
  2. ncbi Chitosan adsorption on hydroxyapatite and its role in preventing acid erosion
    Hyun Su Lee
    Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, United States
    J Colloid Interface Sci 385:235-43. 2012
  3. pmc Correlating macrophage morphology and cytokine production resulting from biomaterial contact
    Hyun Su Lee
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6802, USA
    J Biomed Mater Res A 101:203-12. 2013
  4. pmc Hyaluronan and dextran modified tubes resist cellular activation with blood contact
    David M Eckmann
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA
    Colloids Surf B Biointerfaces 108:44-51. 2013
  5. pmc Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci
    Sana S Dastgheyb
    Department of Orthopaedic Surgery, Jefferson Medical College, 1015 Walnut St, Suite 501, Philadelphia, PA 19107, United States Electronic address
    J Photochem Photobiol B 129:27-35. 2013
  6. pmc Hemocompatibility and biocompatibility of antibacterial biomimetic hybrid films
    M Carme Coll Ferrer
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Toxicol Appl Pharmacol 272:703-12. 2013
  7. pmc Competitive protein adsorption on polysaccharide and hyaluronate modified surfaces
    Michela Ombelli
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biofouling 27:505-18. 2011
  8. pmc Protein assembly at the air-water interface studied by fluorescence microscopy
    Zhengzheng Liao
    Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
    Langmuir 27:12775-81. 2011
  9. pmc Human plasma protein adsorption onto dextranized surfaces: a two-dimensional electrophoresis and mass spectrometry study
    Irene Y Tsai
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104 4283, USA
    Colloids Surf B Biointerfaces 84:241-52. 2011
  10. pmc Symmetric pH-dependent swelling and antibacterial properties of chitosan brushes
    Hyun Su Lee
    Institute of Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Langmuir 27:12458-65. 2011

Scientific Experts

  • David Eckmann
  • Russell J Composto
  • Stanley J Stachelek
  • Michela Ombelli
  • Hyun Su Lee
  • M Carme Coll Ferrer
  • Andres J Calderon
  • Nancy Tomczyk
  • Zhengzheng Liao
  • Joshua W Lampe
  • Davide Miksa
  • Judith Kandel
  • Sana S Dastgheyb
  • Jessie E P Sun
  • Noreen J Hickok
  • Irene Y Tsai
  • Portonovo S Ayyaswamy
  • Ivan J Dmochowski
  • Vladimir Muzykantov
  • Silvia Muro
  • Shunji Kobayashi
  • Peter Sobolewski
  • Matthew J Finley
  • Uriel N Eckmann
  • Paul C Billings
  • Richard Sullivan
  • Chin Chen Kuo
  • Brian Pepe-Mooney
  • James Masters
  • Rustem I Litvinov
  • Craig Streu
  • Justin Vranic
  • Joel S Bennett
  • John W Weisel
  • Shannon Tsai
  • Alice W Bassani
  • Benjamin Pichette
  • Daeyeon Lee
  • Bharat Burman
  • Joshua I Eckmann
  • John Leferovich
  • Tridib Bhowmick
  • Shu Yang
  • Steven Crooks
  • Dwayne Chen
  • Elizabeth R Irish

Detail Information

Publications29

  1. pmc Chemically grafted fibronectin for use in QCM-D cell studies
    Judith Kandel
    Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biosens Bioelectron 58:249-57. 2014
    ..As QCM research with cells has been rather limited in success thus far, we anticipate that this new technique will particularly benefit this experimental system by availing it to the much broader field of cell mechanics. ..
  2. ncbi Chitosan adsorption on hydroxyapatite and its role in preventing acid erosion
    Hyun Su Lee
    Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, United States
    J Colloid Interface Sci 385:235-43. 2012
    ..Both physisorbed and cross-linked chitosan are demonstrated to limit and prevent the erosion of HA, respectively...
  3. pmc Correlating macrophage morphology and cytokine production resulting from biomaterial contact
    Hyun Su Lee
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6802, USA
    J Biomed Mater Res A 101:203-12. 2013
    ..These studies begin to validate the use of GFP-actin-modified MDM as a novel tool to correlate cell morphology with inflammatory cell response...
  4. pmc Hyaluronan and dextran modified tubes resist cellular activation with blood contact
    David M Eckmann
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA
    Colloids Surf B Biointerfaces 108:44-51. 2013
    ..Based on our findings, we suggest that surface coating with hyaluronic acid or dextran acts as a potent shield from blood cellular activation during forms of extracorporeal circulation...
  5. pmc Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci
    Sana S Dastgheyb
    Department of Orthopaedic Surgery, Jefferson Medical College, 1015 Walnut St, Suite 501, Philadelphia, PA 19107, United States Electronic address
    J Photochem Photobiol B 129:27-35. 2013
    ..This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy. ..
  6. pmc Hemocompatibility and biocompatibility of antibacterial biomimetic hybrid films
    M Carme Coll Ferrer
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Toxicol Appl Pharmacol 272:703-12. 2013
    ..These results highlight low toxicity of DEX-Ag and hold promise for future applications in vivo...
  7. pmc Competitive protein adsorption on polysaccharide and hyaluronate modified surfaces
    Michela Ombelli
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biofouling 27:505-18. 2011
    ..With changing bulk protein concentration from 20 to 40 μg ml(-1) for each species, Fg coverage on silicon increased by 4x, whereas both BSA and Fg adsorption on dextran and HA were far less dependent on protein bulk concentration...
  8. pmc Protein assembly at the air-water interface studied by fluorescence microscopy
    Zhengzheng Liao
    Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
    Langmuir 27:12775-81. 2011
    ..Protein domains were observed to coalesce during this competitive adsorption process...
  9. pmc Human plasma protein adsorption onto dextranized surfaces: a two-dimensional electrophoresis and mass spectrometry study
    Irene Y Tsai
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104 4283, USA
    Colloids Surf B Biointerfaces 84:241-52. 2011
    ..In summary, these studies indicate that coating blood-contacting biomedical applications with dextran is an effective route to reduce thrombo-inflammatory responses and to surface-direct biological activities...
  10. pmc Symmetric pH-dependent swelling and antibacterial properties of chitosan brushes
    Hyun Su Lee
    Institute of Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Langmuir 27:12458-65. 2011
    ..This antibacterial characteristic of CH-Q is attributed to the quaternary ammonium salts and the flexible polymer brush...
  11. pmc The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation
    Stanley J Stachelek
    Division of Cardiology, Department of Pediatrics, The Children s Hospital of Philadelphia, PA, USA
    Biomaterials 32:4317-26. 2011
    ..In conclusion, CD47 functionalized surfaces can resist inflammatory cell interactions both in vitro and in vivo...
  12. pmc Optimizing endothelial targeting by modulating the antibody density and particle concentration of anti-ICAM coated carriers
    Andres J Calderon
    Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    J Control Release 150:37-44. 2011
    ..These results will guide optimization of ICAM-1-targeted carriers, e.g., in the context of targeting healthy vs diseased endothelium for prophylactic vs therapeutic interventions...
  13. pmc Imaging macromolecular interactions at an interface
    Joshua W Lampe
    Center for Resuscitation Science, Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Langmuir 26:2452-9. 2010
    ....
  14. pmc Bimolecular integrin-ligand interactions quantified using peptide-functionalized dextran-coated microparticles
    Jessie E P Sun
    Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Integr Biol (Camb) 4:84-92. 2012
    ..Thus, the results reported here describe the mechanistic characteristics of αIIbβ3-ligand interactions, confirming the utility of peptide-functionalized latex beads for the quantitative analysis of molecular recognition...
  15. pmc Creating biomimetic polymeric surfaces by photochemical attachment and patterning of dextran
    M Carme Coll Ferrer
    Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6202, USA
    Langmuir 26:14126-34. 2010
    ..The antifouling properties of dextran functionalized surfaces were verified by the selective adsorption of FITC-labeled human albumin only on the nondextranized regions of the patterned polyurethane and polystyrene substrates...
  16. ncbi Gas embolism and surfactant-based intervention: implications for long-duration space-based activity
    David M Eckmann
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1077:256-69. 2006
    ..Special consideration is given to modeling the transport and hydrodynamic interactions associated with surfactant-based intervention...
  17. ncbi Microvascular embolization following polidocanol microfoam sclerosant administration
    David M Eckmann
    Department of Anestthesia, The University of Pennsylvania, PA 19104, USA
    Dermatol Surg 31:636-43. 2005
    ..Intravenous microfoam sclerotherapy solutions can potentially cause cerebrovascular arterial embolization...
  18. ncbi A quantitative and selective chromatography method for determining coverages of multiple proteins on surfaces
    Michela Ombelli
    Department of Anesthesia, University of Pennsylvania, 319B John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 826:198-205. 2005
    ..Relative to silicon, the dextranized surfaces were found to strongly inhibit protein adsorption, decreasing BSA and Fg coverages by 76 and 60%, respectively...
  19. ncbi Dextran functionalized surfaces via reductive amination: morphology, wetting, and adhesion
    Davide Miksa
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, 19104, USA
    Biomacromolecules 7:557-64. 2006
    ..Overall, film morphology and wetting behavior were relatively invariant with grafting density, confirming the method's robustness for preparing biomimetic coatings with consistent properties...
  20. ncbi Influence of endothelial glycocalyx degradation and surfactants on air embolism adhesion
    David M Eckmann
    Department of Anesthesiology and Critical Care, Institute for Medicine and Engineering, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Anesthesiology 105:1220-7. 2006
    ..The authors tested the hypothesis that exogenous surfactants delivered intravascularly have differential effects on the rate of restoration of blood flow after heparinase-induced degradation of the endothelial glycocalyx...
  21. pmc Flow dynamics, binding and detachment of spherical carriers targeted to ICAM-1 on endothelial cells
    Andres J Calderon
    Department of Anesthesiology and Critical Care, University of Pennsylvania Medical School, Philadelphia, PA, USA
    Biorheology 46:323-41. 2009
    ..This is further supported by theoretical modeling. These results will guide vascular targeting of drug carriers via rational design of experimentally tunable parameters...
  22. ncbi Dose- and time-dependent liquid sclerosant effects on endothelial cell death
    Shunji Kobayashi
    Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
    Dermatol Surg 32:1444-52. 2006
    ..Intravenous sclerotherapy solutions can induce endothelial cell death...