PMID- 22088814
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20191210
IS  - 1532-7361 (Electronic)
IS  - 0039-6060 (Linking)
VI  - 151
IP  - 3
DP  - 2012 Mar
TI  - Decrease in donor heart injury by recombinant clusterin protein in cold 
      preservation with University of Wisconsin solution.
PG  - 364-71
LID - 10.1016/j.surg.2011.09.032 [doi]
AB  - BACKGROUND: Donor organ injury during cold preservation before transplantation 
      negatively impacts graft survival. Clusterin (CLU) is a chaperonic protein, and 
      its expression confers donor hearts resistance to cold ischemic injury. This 
      study was conducted to evaluate if the supplement of recombinant CLU protein 
      (rCLU) protects donor organs from injury during cold storage with University of 
      Wisconsin (UW) solution. METHODS: Human endothelial cell cultures were used as an 
      in vitro model. Heart transplantation in mice was used as an in vivo model. Cell 
      membrane disruption or death was indicated by the release of lactate 
      dehydrogenase (LDH). Donor injury was determined by its functional recovery, and 
      histologic and biochemical analyses. RESULTS: Supplement of rCLU to UW solution 
      protected cultured human endothelial cells from cold-induced cell necrosis, as 
      evidenced by a decrease in both release of LDH and the number of ethidium 
      bromide-stained necrotic cells. The protective activity of rCLU was associated 
      with enhanced membrane fluidity at cold temperature. During cold storage of heart 
      organs in UW solution, supplemental rCLU significantly decreased LDH release from 
      heart tissue. In a preclinical model of transplantation, heart grafts after cold 
      preservation with rCLU-containing UW solution had better functional recovery and 
      decreased perivascular inflammation, neutrophil infiltration, and cardiac cell 
      death, including apoptosis and necrosis, that correlated with lower levels of 
      serum creatine kinase and LDH in recipients. CONCLUSION: Our data suggest that 
      supplement of CLU protein in a cold preservation solution may have potential in 
      improving cold preservation of donor organs in transplantation.
CI  - Copyright A(c) 2012 Mosby, Inc. All rights reserved.
FAU - Guan, Qiunong
AU  - Guan Q
AD  - Department of Urologic Sciences, University of British Columbia, Immunity and 
      Infection Research Centre, Vancouver Coastal Health Research Institute, and the 
      Vancouver Prostate Centre, Vancouver, BC, Canada.
FAU - Li, Shuyuan
AU  - Li S
FAU - Yip, Gordon
AU  - Yip G
FAU - Gleave, Martin E
AU  - Gleave ME
FAU - Nguan, Christopher Y C
AU  - Nguan CY
FAU - Du, Caigan
AU  - Du C
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111116
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - 0 (CLU protein, human)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Clusterin)
RN  - 0 (Insulin)
RN  - 0 (Organ Preservation Solutions)
RN  - 0 (Recombinant Proteins)
RN  - 0 (University of Wisconsin-lactobionate solution)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - GAN16C9B8O (Glutathione)
RN  - K72T3FS567 (Adenosine)
RN  - N5O3QU595M (Raffinose)
SB  - IM
MH  - Adenosine
MH  - Allopurinol
MH  - Animals
MH  - Cardiotonic Agents/pharmacology
MH  - Cell Membrane/drug effects/metabolism/pathology
MH  - Clusterin/*pharmacology
MH  - Cold Ischemia
MH  - Glutathione
MH  - Graft Survival/drug effects
MH  - Heart Transplantation/*methods/pathology/physiology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Insulin
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - Membrane Fluidity/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/enzymology/pathology
MH  - Neutrophil Infiltration/drug effects
MH  - Organ Preservation/*methods
MH  - *Organ Preservation Solutions
MH  - Raffinose
MH  - Recombinant Proteins/pharmacology
EDAT- 2011/11/18 06:00
MHDA- 2012/04/10 06:00
CRDT- 2011/11/18 06:00
PHST- 2011/05/11 00:00 [received]
PHST- 2011/09/22 00:00 [accepted]
PHST- 2011/11/18 06:00 [entrez]
PHST- 2011/11/18 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
AID - S0039-6060(11)00546-0 [pii]
AID - 10.1016/j.surg.2011.09.032 [doi]
PST - ppublish
SO  - Surgery. 2012 Mar;151(3):364-71. doi: 10.1016/j.surg.2011.09.032. Epub 2011 Nov 
      16.