Ischemic preconditioning of cadaver donor livers protects allografts following transplantation

Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts. Cadaveric donor livers were subjected to IP prio...

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Veröffentlicht in:Transplantation Jg. 81; H. 2; S. 169
Hauptverfasser: Jassem, Wayel, Fuggle, Susan V, Cerundolo, Lucia, Heaton, Nigel D, Rela, Mohamed
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.01.2006
Schlagworte:
Adult
Aged
Animals
Blood Platelets - pathology
Cadaver
Case-Control Studies
Female
Graft Survival
Humans
Ischemic Preconditioning - methods
Liver - injuries
Liver - pathology
Liver - physiopathology
Liver Transplantation - methods
Liver Transplantation - pathology
Liver Transplantation - physiology
Male
Middle Aged
Neutrophils - pathology
Reperfusion Injury - prevention & control
Transplantation, Homologous
ISSN:0041-1337
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Abstract Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts. Cadaveric donor livers were subjected to IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by reperfusion. Biopsies were obtained from the preconditioned (n=9) and control nonpreconditioned (n=14) liver transplants prior to and 2 hr following reperfusion. Cryosections were stained with antibodies against neutrophils and platelets. IP livers were associated with significantly lower serum levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016) and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following transplantation. Furthermore, recipients of IP livers spent a significantly shorter time in the intensive care unit following transplantation compared to those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008). Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none of the IP allografts showed any change in the levels of platelets or neutrophil infiltration following transplantation. IP is an effective method of protecting cadaver donor allografts from cold ischemia and subsequent reperfusion injury. IP is also associated with a reduction in the nonspecific inflammatory response.
AbstractList Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts.BACKGROUNDIschemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts.Cadaveric donor livers were subjected to IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by reperfusion. Biopsies were obtained from the preconditioned (n=9) and control nonpreconditioned (n=14) liver transplants prior to and 2 hr following reperfusion. Cryosections were stained with antibodies against neutrophils and platelets.METHODSCadaveric donor livers were subjected to IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by reperfusion. Biopsies were obtained from the preconditioned (n=9) and control nonpreconditioned (n=14) liver transplants prior to and 2 hr following reperfusion. Cryosections were stained with antibodies against neutrophils and platelets.IP livers were associated with significantly lower serum levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016) and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following transplantation. Furthermore, recipients of IP livers spent a significantly shorter time in the intensive care unit following transplantation compared to those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008). Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none of the IP allografts showed any change in the levels of platelets or neutrophil infiltration following transplantation.RESULTSIP livers were associated with significantly lower serum levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016) and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following transplantation. Furthermore, recipients of IP livers spent a significantly shorter time in the intensive care unit following transplantation compared to those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008). Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none of the IP allografts showed any change in the levels of platelets or neutrophil infiltration following transplantation.IP is an effective method of protecting cadaver donor allografts from cold ischemia and subsequent reperfusion injury. IP is also associated with a reduction in the nonspecific inflammatory response.CONCLUSIONIP is an effective method of protecting cadaver donor allografts from cold ischemia and subsequent reperfusion injury. IP is also associated with a reduction in the nonspecific inflammatory response.
Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to investigate whether IP of cadaver livers prior to retrieval confers protection on the allografts. Cadaveric donor livers were subjected to IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by reperfusion. Biopsies were obtained from the preconditioned (n=9) and control nonpreconditioned (n=14) liver transplants prior to and 2 hr following reperfusion. Cryosections were stained with antibodies against neutrophils and platelets. IP livers were associated with significantly lower serum levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016) and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following transplantation. Furthermore, recipients of IP livers spent a significantly shorter time in the intensive care unit following transplantation compared to those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008). Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none of the IP allografts showed any change in the levels of platelets or neutrophil infiltration following transplantation. IP is an effective method of protecting cadaver donor allografts from cold ischemia and subsequent reperfusion injury. IP is also associated with a reduction in the nonspecific inflammatory response.
Author Fuggle, Susan V
Rela, Mohamed
Jassem, Wayel
Cerundolo, Lucia
Heaton, Nigel D
Author_xml – sequence: 1
  givenname: Wayel
  surname: Jassem
  fullname: Jassem, Wayel
  email: wayel.jassem@kcl.ac.uk
  organization: Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, United Kingdom. wayel.jassem@kcl.ac.uk
– sequence: 2
  givenname: Susan V
  surname: Fuggle
  fullname: Fuggle, Susan V
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  givenname: Lucia
  surname: Cerundolo
  fullname: Cerundolo, Lucia
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  givenname: Nigel D
  surname: Heaton
  fullname: Heaton, Nigel D
– sequence: 5
  givenname: Mohamed
  surname: Rela
  fullname: Rela, Mohamed
BackLink https://www.ncbi.nlm.nih.gov/pubmed/16436958$$D View this record in MEDLINE/PubMed
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Snippet Ischemic preconditioning (IP) has been shown in animal models to protect livers against ischemia/reperfusion injury. The aim of this clinical study is to...
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SubjectTerms Adult
Aged
Animals
Blood Platelets - pathology
Cadaver
Case-Control Studies
Female
Graft Survival
Humans
Ischemic Preconditioning - methods
Liver - injuries
Liver - pathology
Liver - physiopathology
Liver Transplantation - methods
Liver Transplantation - pathology
Liver Transplantation - physiology
Male
Middle Aged
Neutrophils - pathology
Reperfusion Injury - prevention & control
Transplantation, Homologous
Title Ischemic preconditioning of cadaver donor livers protects allografts following transplantation
URI https://www.ncbi.nlm.nih.gov/pubmed/16436958
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