A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.
Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the ac...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3077371?pdf=render |
| _version_ | 1818964827130822656 |
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| author | Feng Ding Joon Ho Song Ju Young Jung Liandi Lou Min Wang Linda Charles Angela Westover Peter L Smith Christopher J Pino Deborah A Buffington H David Humes |
| author_facet | Feng Ding Joon Ho Song Ju Young Jung Liandi Lou Min Wang Linda Charles Angela Westover Peter L Smith Christopher J Pino Deborah A Buffington H David Humes |
| author_sort | Feng Ding |
| collection | DOAJ |
| description | Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD), was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis.Laboratory investigation.University of Michigan Medical School.Pigs weighing 30-35 kg.To assess the effect of the SCD in septic shock, pigs were administered 30×10(10) bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD.In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation.These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway. |
| first_indexed | 2024-12-20T13:07:18Z |
| format | Article |
| id | doaj.art-38014fe617d64ab69af064a9ad50040d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T13:07:18Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-38014fe617d64ab69af064a9ad50040d2022-12-21T19:39:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1858410.1371/journal.pone.0018584A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.Feng DingJoon Ho SongJu Young JungLiandi LouMin WangLinda CharlesAngela WestoverPeter L SmithChristopher J PinoDeborah A BuffingtonH David HumesSeptic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD), was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis.Laboratory investigation.University of Michigan Medical School.Pigs weighing 30-35 kg.To assess the effect of the SCD in septic shock, pigs were administered 30×10(10) bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD.In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation.These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway.http://europepmc.org/articles/PMC3077371?pdf=render |
| spellingShingle | Feng Ding Joon Ho Song Ju Young Jung Liandi Lou Min Wang Linda Charles Angela Westover Peter L Smith Christopher J Pino Deborah A Buffington H David Humes A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. PLoS ONE |
| title | A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. |
| title_full | A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. |
| title_fullStr | A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. |
| title_full_unstemmed | A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. |
| title_short | A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. |
| title_sort | biomimetic membrane device that modulates the excessive inflammatory response to sepsis |
| url | http://europepmc.org/articles/PMC3077371?pdf=render |
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