Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

Olthof, Pim B.; Reiniers, Megan J.; Dirkes, Marcel C.; Gulik, Thomas M. van; Heger, Michal; Golen, Rowan F. van

doi:10.2119/molmed.2015.00158

Cited by 31 publications

(21 citation statements)

References 109 publications

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“…The marked syndecan-1 efflux from the liver graft may reflect glycocalyx degradation occurring both during graft cold preservation and reperfusion. In experimental models of liver IR-injury, sinusoidal endothelial cells appear particularly sensitive to cold ischemia [17] and glycocalyx damage in the sinusoids has been described during cold preservation [18]. Thus, the syndecan-1 efflux during reperfusion demonstrated in our patients potentially reflects a washout of glycocalyx degradation products accumulated in the graft during cold preservation.…”

Section: Discussionmentioning

confidence: 79%

Graft glycocalyx degradation in human liver transplantation

et al. 2019

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Objective Ischaemia/reperfusion-injury degrades endothelial glycocalyx. Graft glycocalyx degradation was studied in human liver transplantation. Methods To assess changes within the graft, blood was drawn from portal and hepatic veins in addition to systemic samples in 10 patients. Plasma syndecan-1, heparan sulfate and chondroitin sulfate, were measured with enzyme-linked immunosorbent assay. Results During reperfusion, syndecan-1 levels were higher in graft caval effluent [3118 (934–6141) ng/ml, P = 0.005] than in portal venous blood [101 (75–121) ng/ml], indicating syndecan-1 release from the graft. Concomitantly, heparan sulfate levels were lower in graft caval effluent [96 (32–129) ng/ml, P = 0.037] than in portal venous blood [112 (98–128) ng/ml], indicating heparan sulfate uptake within the graft. Chondroitin sulfate levels were equal in portal and hepatic venous blood. After reperfusion arterial syndecan-1 levels increased 17-fold (P < 0.001) and heparan sulfate decreased to a third (P < 0.001) towards the end of surgery. Conclusion Syndecan-1 washout from the liver indicates extensive glycocalyx degradation within the graft during reperfusion. Surprisingly, heparan sulfate was taken up by the graft during reperfusion. Corroborating previous experimental reports, this suggests that endogenous heparan sulfate might be utilized within the graft in the repair of damaged glycocalyx.

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Section: Discussionmentioning

confidence: 79%

Graft glycocalyx degradation in human liver transplantation

et al. 2019

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“…Excessive blood loss during surgery is associated with poor postoperative outcomes (2); to avoid this, vascular inflow occlusion (VIO) is often performed during liver transaction (3). Although VIO effectively reduces blood loss, hepatic oxygen supply is interrupted, which results in metabolic disruption that subjects the liver to hepatic ischemia/reperfusion (I/R) injury once oxygen is reintroduced (4).…”

Section: Introductionmentioning

confidence: 99%

CD5L‑induced activation of autophagy is associated with hepatoprotection in ischemic reperfusion injury via the CD36/ATG7 axis

Lin

Zhuang

2020

Exp Ther Med

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Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that is difficult to prevent. I/R injury induces metabolic strain on hepatocytes and limits the tolerable ischemia during liver resection, as well as preservation times during transplantation. Additionally, I/R injury induces apoptosis in hepatocytes. CD5-like (CD5L), an inducer of autophagy, is a soluble scavenger cysteine-rich protein that modulates hepatocyte apoptosis. The aim of the present study was to determine if pharmacologic CD5L was protective against hepatic ischemia-reperfusion injury. Hepatocytes were subjected to I/R culture conditions, and apoptosis and caspase family activity were measured after I/R to model hepatic injury. Treatment with recombinant CD5L significantly suppressed apoptosis and caspase activity through modulating cellular autophagy to maintain activation of the cluster of differentiation 36 (CD36)-dependent autophagy-related 7 (ATG7) signaling pathway. The regulation loop between CD5L and the autophagy signaling pathway was identified to be associated with the inhibition of oxidative stress. Treatment with CD5L significantly inhibited cellular oxidative stress, which was confirmed by silencing the CD36 receptor or the autophagy related protein ATG7 using small interfering RNA, which reversed the antiapoptotic and antioxidative effects of CD5L on hepatocytes under I/R conditions. The results of the present study suggested that CD5L-mediated attenuation of hepatic I/R injury occurs through the CD36-dependent ATG7 pathway, accompanied by the inhibition of oxidative stress, which is associated with enhanced autophagy. In conclusion, the present study identifies CD5L as a novel therapeutic agent for hepatic I/R injury.

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“…Induction of hypothermia has the potential to reduce I/R injuries after organ reperfusion, potentially preventing liver failure in the postoperative period 7 . However, an incomplete understanding of the underlying protective mechanisms has limited a uniform and widespread implementation of liver-cooling techniques 8 . Mild hypothermia has consistently shown to provide protection against hepatic injury in different experimental models [9][10][11] .…”

Section: ■ Introductionmentioning

confidence: 99%