Document Detail


A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs.
MedLine Citation:
PMID:  19058891     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Haemorrhagic shock causes ischaemia and subsequent fluid resuscitation causes reperfusion injury, jointly resulting in high morbidity and mortality. We tested whether the anti-inflammatory fibrin-derived peptide, Bbeta(15-42), also called FX06, is tissue protective in a model of haemorrhagic shock. METHODS: In a pig model, we standardised the severity of haemorrhagic shock by achieving a cumulative oxygen deficit of approximately 100ml/kg body weight by withdrawing blood over a period of 1h. This was followed by resuscitation with shed blood and full electrolyte solution, and pigs were monitored for 3 days. At reperfusion, 17 pigs were randomly assigned to FX06 or solvent treatment. RESULTS: FX06-treated pigs demonstrated improved cardiac function (stroke volume index: 67ml/m(2) versus 33ml/m(2)), decreased troponin T release in the early reperfusion (0.24ng/ml versus 0.78ng/ml), decreased AST levels after 24h (106U/l versus 189U/l) and decreased creatinine levels after 24h (108micromol/l versus 159micromol/l). Furthermore, FX06-treated pigs demonstrated preservation of the gut/blood barrier, while controls demonstrated high endotoxin plasma levels indicating translocation of bacteria and/or its products (0.2EU/ml versus 24.3EU/ml) after 24h. This study also demonstrates a significantly improved neurological performance in the FX06 group as determined by S100beta serum levels (0.72microg/l versus 1.25microg/l) after 48h and neurological deficit scores (11 versus 70) after 24h. CONCLUSION: FX06 - when administered as an adjunct to fluid resuscitation therapy - is organ protective in pigs. Further investigations are warranted to reveal the protective mechanism of FX06.
Authors:
Jan P Roesner; Peter Petzelbauer; Alexander Koch; Nguyen Tran; Thomas Iber; Christian Mutz; Brigitte Vollmar; Gabriele E F Nöldge-Schomburg; Kai Zacharowski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-05
Journal Detail:
Title:  Resuscitation     Volume:  80     ISSN:  0300-9572     ISO Abbreviation:  Resuscitation     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-19     Completed Date:  2009-05-15     Revised Date:  2009-08-25    
Medline Journal Info:
Nlm Unique ID:  0332173     Medline TA:  Resuscitation     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  264-71     Citation Subset:  IM    
Affiliation:
Department of Anaesthesia and Intensive Care Medicine, University Hospital Rostock, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / pharmacology*
Aspartate Aminotransferases / blood
Blood Glucose / analysis
Blood Urea Nitrogen
Creatine Kinase / blood
Disease Models, Animal
Double-Blind Method
Drug Evaluation, Preclinical
Endotoxins / blood
Fibrin Fibrinogen Degradation Products / pharmacology*
Glutamate Dehydrogenase / blood
Interleukins / blood
L-Lactate Dehydrogenase / blood
Leukocyte Count
Male
Nerve Growth Factors / blood
Neurologic Examination
Oxygen / blood
Peptide Fragments / pharmacology*
Pulmonary Gas Exchange
Random Allocation
Reperfusion / methods*
Resuscitation
S100 Proteins / blood
Shock, Hemorrhagic / drug therapy*
Stroke Volume / drug effects
Swine
Troponin T / blood
Tumor Necrosis Factor-alpha / blood
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Blood Glucose; 0/Endotoxins; 0/Fibrin Fibrinogen Degradation Products; 0/Interleukins; 0/Nerve Growth Factors; 0/Peptide Fragments; 0/S-100 calcium-binding protein beta subunit; 0/S100 Proteins; 0/Troponin T; 0/Tumor Necrosis Factor-alpha; 0/fibrinogen Bbeta (15-42); 7782-44-7/Oxygen; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.4.1.2/Glutamate Dehydrogenase; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.7.3.2/Creatine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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