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PRODID:-//Columba Systems Ltd//NONSGML CPNG/SpringViewer/ICal Output/3.3-
 M3//EN
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METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20160201T153359Z
DTSTART:20160208T153000Z
DTEND:20160208T163000Z
SUMMARY:MCCIR AZ GSK Update Seminar Series
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}g16p-ik44zh
 7u-c0mmhf
DESCRIPTION:The next MCCIR AZ/GSK Update Seminar is taking place on Monda
 y the 8th of February 2016\n\nAltered immunogenicity of porcine hearts v
 ia ex vivo perfusion \n\nWill Critchley\n\nThere are approximately 1.8 m
 illion patients living with heart failure in the UK. Heart transplantati
 on still represents the only effective treatment for patients with end s
 tage disease who are refractory to maximal treatment. However\, the numb
 er of transplants performed is limited by the availability of suitable d
 onor organs leading to high mortality on the waiting list. Increasing th
 e utilisation of available organs may require the use of marginal\, high
 er risk donors including donation after circulatory death. Ex vivo heart
  perfusion was developed as a method to improve preservation and aid eva
 luation of potential donor organs. However\, the process of perfusion ma
 y have auxiliary benefits beyond extended preservation. This study inves
 tigated the effect of 8 hours of ex vivo perfusion on myocardial immune 
 content to determine whether passenger leukocyte transfer would be modul
 ated. We demonstrate that ex vivo perfusion results in a significant red
 uction in donor organ immunogenicity via the removal of passenger leukoc
 ytes. This appears to occur in a selective manner in response to circula
 ting cytokines/chemokines released into the circuit\, which may saturate
  the inflammatory response of the organ prior to transplantation. Additi
 onally\, ex vivo perfusion of the organ induces improvements in tissue s
 tatus at a molecular level compared to baseline\, indicating that this p
 rocess is sufficient to maintain the organ in a transplantable condition
  over 8 hours\, which is a significant improvement over current methods.
 \n\n\nIs NLRP3 inflammasome activation involved in irreversible acute lu
 ng injury?\n\nTriin Major\n\nEx vivo lung perfusion (EVLP) is a techniqu
 e used to evaluate and recondition marginal donor lungs that otherwise w
 ould be discarded for transplantation. We have identified that interleuk
 in-1? (IL-1 ?) can be used as a prognostic indicator of non-recovery dur
 ing clinical EVLP. IL-1? is a pro-inflammatory cytokine that can contrib
 ute to acute tissue injury. Its secretion is dependent on inflammasome a
 ssembly\, so we hypothesised that inflammasome inhibitor therapy could r
 epresent a novel strategy to prevent acute lung injury during EVLP. We p
 erformed a double blinded randomised study using an NLRP3 inflammasome i
 nhibitor during porcine EVLP. ASC+ inflammasome particles were measured 
 as an indicator of inflammasome activity\, and the cellular outflow and 
 cytokine profile of the organs were assessed. Whilst we demonstrated a d
 ecrease in inflammasome particles\, there were no differences between th
 e control and the inhibitor groups in terms of cytokine profile\, cellul
 ar outflow or organ function.  We then repeated the treatment using kidn
 ey perfusion to determine if this was an organ-specific phenomenon\, but
  again found that inflammasome inhibition had no impact on IL-1? or rena
 l function. As the concentration of IL-1? increased during both lung and
  kidney perfusion despite inflammasome inhibition\, we then measured pro
 -IL-1?\, the inactive intracellular precursor molecule. In (n=10) human 
 lungs that did not recondition and were rejected for transplant\, a sign
 ificant increase in pro-IL-1? was detected (compared to n=10 lungs that 
 reconditioned and were used for transplantation). This suggests that pro
 -IL-1? is released following necrosis or necroptosis rather than activel
 y secreted as part of a specific inflammatory process. We now aim to ass
 ess the mechanism of cell death in non-recoverable donor lungs and perfo
 rm additional studies using inhibitors of necrosis and necroptosis.\n
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Michael Smith Lecture Theatre\, Michael Smith Building\, Manches
 ter
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