Molecular expression of acute phase mediators is attenuated by machine preservation in human liver transplantation: Preliminary analysis of effluent, serum, and liver biopsies

Tulipan, Jacob; Stone, J G; Samstein, Benjamin; Kato, Tomoaki; Emond, Jean C.; Henry, Scot D.; Guarrera, James V.

doi:10.1016/j.surg.2011.06.003

Cited by 34 publications

(22 citation statements)

References 17 publications

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“…development of a portable device that can be applied at the time of organ recovery may further improve outcomes. We attribute our improved clinical outcomes (3) and molecular results (5,16), coupled with our present findings to the ability of HMP to maintain homeostasis and provide both nutrients and oxygen while also removing/diluting waste products away from the graft. The particular removal of precursor pro-inflammatory cytokines such as TNFa, IL-1b and IL-8 prevents the activation of other major downstream cytokine, chemokine and immune cell pathways which would normally negatively affect graft function.…”

Section: Scs Atsupporting

confidence: 68%

“…The current understanding of IRI cascades in human liver transplantation is currently limited to the extrapolation of data from animal studies. Therefore, we present here a molecular analysis of the first human clinical HMP trial in an effort to elucidate the exact mechanisms of the improved outcomes we have observed clinically and preliminarily (3,16).…”

Section: Scs Atmentioning

confidence: 99%

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Hypothermic Machine Preservation Reduces Molecular Markers of Ischemia/Reperfusion Injury in Human Liver Transplantation

Henry

Nachber

Tulipan

et al. 2012

American Journal of Transplantation

138

121

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Hypothermic machine perfusion (HMP) is in its infancyin clinical liver transplantation. Potential benefits include diminished preservation injury (PI) and improved graft function. Molecular data to date has been limited to extrapolation of animal studies. We analyzed liver tissue and serum collected during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to static cold stored (SCS) transplant controls. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and transmission electron microscopy (TEM) were performed on liver biopsies. Expression of inflammatory cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and acute phase proteins and the levels of CD68 positive macrophages in tissue sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group showed high expression of inflammatory cytokines, adhesion molecules and chemokines, oxidative markers and acute phase proteins. This upregulation was significantly attenuated in livers that were preserved by HMP. Immunofluorescence showed larger numbers of CD68 positive macrophages in the SCS group when compared to the HMP group. TEM samples also revealed ultrastructural damage in the SCS group that was not seen in the HMP group. HMP significantly reduced proinflammatory cytokine expression, relieving the downstream activation of adhesion molecules and migration of leukocytes, including neutrophils and macrophages when compared to SCS controls.

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Section: Scs Atsupporting

confidence: 68%

Section: Scs Atmentioning

confidence: 99%

Hypothermic Machine Preservation Reduces Molecular Markers of Ischemia/Reperfusion Injury in Human Liver Transplantation

Henry

Nachber

Tulipan

et al. 2012

American Journal of Transplantation

138

121

View full text Add to dashboard Cite

show abstract

“…Our pilot study demonstrated feasibility, safety and efficacy with diminished peak injury markers, lower length of hospital stay, a trend toward less early allograft dysfunction (EAD) and fewer biliary complications. We also reported that HMP attenuates the classical molecular ischemia/reperfusion markers of liver preservation injury and improves hepatic ultrastructural preservation in comparison with cold storage (5,6).…”

Section: Introductionmentioning

confidence: 68%

“…HMP provides a continuous flow of metabolic substrates and antioxidants, while flushing cytokines, proteins and toxins from the liver. This attenuates the cytokine mediated ischemia/reperfusion damage cascade build-up that occurs within a statically preserved liver (2)(3)(4)(5)(6). Our pilot study demonstrated feasibility, safety and efficacy with diminished peak injury markers, lower length of hospital stay, a trend toward less early allograft dysfunction (EAD) and fewer biliary complications.…”

Section: Introductionmentioning

confidence: 76%

Hypothermic Machine Preservation Facilitates Successful Transplantation of “Orphan” Extended Criteria Donor Livers

Guarrera

Henry

Samstein

et al. 2015

American Journal of Transplantation

276

272

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Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used to preserve kidneys for transplantation with improved results over static cold storage (SCS). At our center, we have used HMP in 31 adults receiving extended criteria donor (ECD) livers declined by the originating United Network for Organ Sharing region (''orphan livers''). These cases were compared to ECD SCS cases in a matched cohort study design. Livers were matched for donor age, recipient age, cold ischemic time, donor risk index and Model for EndStage Liver Disease (MELD) score. HMP was performed for 3-7 h at 4-88C using our previously published protocol. Early allograft dysfunction rates were 19% in the HMP group versus 30% in the control group (p ¼ 0.384). One-year patient survival was 84% in the HMP group versus 80% in the SCS group (p ¼ NS). Post hoc analysis revealed significantly less biliary complications in the HMP group versus the SCS group (4 vs. 13, p ¼ 0.016). Mean hospital stay was significantly shorter in the HMP group (13.64 AE 10.9 vs. 20.14 AE 11.12 days in the SCS group, p ¼ 0.001). HMP provided safe and reliable preservation in orphan livers transplanted at our center.

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“…Importantly, and as related to graft assessment, ALT release per gram of liver during HMP correlates with the release of ALT during reperfusion injury after transplantation [16]. Furthermore, effluent analysis during HMP allows the determination of several acute phase reactants [38]. …”

Section: Assessment Of Liver Injury During Hypothermic Machine Liver mentioning

confidence: 99%

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

2015

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Dynamic preservation strategies such as hypothermic machine perfusion are increasingly discussed to improve liver graft quality before transplantation. This review summarizes current knowledge of this perfusion technique for liver preservation. We discuss optimization of perfusion conditions and current strategies to assess graft quality during cold perfusion. Next, we provide an overview of possible pathways of protection from ischemia-reperfusion injury. Finally, we report on recent clinical applications of human hypothermic machine liver perfusion.

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Molecular expression of acute phase mediators is attenuated by machine preservation in human liver transplantation: Preliminary analysis of effluent, serum, and liver biopsies

Cited by 34 publications

References 17 publications

Hypothermic Machine Preservation Reduces Molecular Markers of Ischemia/Reperfusion Injury in Human Liver Transplantation

Hypothermic Machine Preservation Reduces Molecular Markers of Ischemia/Reperfusion Injury in Human Liver Transplantation

Hypothermic Machine Preservation Facilitates Successful Transplantation of “Orphan” Extended Criteria Donor Livers

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

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