Cholangiocyte Epithelial to Mesenchymal Transition (EMT) is a potential molecular mechanism driving ischemic cholangiopathy in liver transplantation.

Donation after circulatory death (DCD) has expanded the donor pool for liver transplantation. However, ischemic cholangiopathy (IC) after DCD liver transplantation causes inferior outcomes. The molecular mechanisms of IC are currently unknown but may depend on ischemia-induced genetic reprograming of the biliary epithelium to mesenchymal-like cells.

Donor gluconate rescues livers from uncontrolled donation after cardiac death.

Background: Ischemia from organ preservation or donation causes cells and tissues to swell owing to loss of energy-dependent mechanisms of control of cell volume. These volume changes cause substantial preservation injury, because preventing these changes by adding cell impermeants to preservation solutions decreases preservation injury. The objective of this study was to assess if this effect could be realized early in uncontrolled donation after cardiac death (DCD) livers by systemically loading donors with gluconate immediately after death to prevent accelerated swelling injury during the warm ischemia period before liver retrieval.

New low-volume resuscitation solutions containing PEG-20k.

Background: Hypovolemic shock reduces oxygen delivery and compromises energy-dependent cell volume control. Consequent cell swelling compromises microcirculatory flow, which reduces oxygen exchange further. The importance of this mechanism is highlighted by the effectiveness of cell impermeants in low-volume resuscitation (LVR) solutions in acute studies.

Cell Impermeant-based Low-volume Resuscitation in Hemorrhagic Shock: A Biological Basis for Injury Involving Cell Swelling.

Objective: To determine the role of cell swelling in severe hemorrhagic shock and resuscitation injury.

Background: Circulatory shock induces the loss of energy-dependent volume control mechanisms. As water enters ischemic cells, they swell, die, and compress nearby vascular structures, which further aggravates ischemia by reducing local microcirculatory flow and oxygenation.

Moesin functionality in hypothermic liver preservation injury.

The objective of this study was to determine how expression and functionality of the cytoskeletal linker protein moesin is involved in hepatic hypothermic preservation injury. Mouse livers were cold stored in University of Wisconsin (UW) solution and reperfused on an isolated perfused liver (IPL) device for one hour. Human hepatocytes (HepG2) and human or murine sinusoidal endothelial cells (SECs) were cold stored and rewarmed to induce hypothermic preservation injury.

Hypothermic Machine Perfusion Preservation of the DCD Kidney: Machine Effects.

Purpose. Kidneys from DCD donors represent a significant pool, but preservation problems exist. The study objective was to test the importance of machine type for hypothermic preservation of DCD kidneys.

Ezrin functionality and hypothermic preservation injury in LLC-PK1 cells.

Renal epithelial cells from donor kidneys are susceptible to hypothermic preservation injury, which is attenuated when they over express the cytoskeletal linker protein ezrin. This study was designed to characterize the mechanisms of this protection. Renal epithelial cell lines were created from LLC-PK1 cells, which expressed mutant forms of ezrin with site directed alterations in membrane binding functionality.

Mouse IPK: A Powerful Tool to Partially Characterize Renal Reperfusion and Preservation Injury.

Main Problem: The molecular basis of renal preservation injury is not well understood. Since mouse kidney transplantation models are not useful in this setting, a mouse Isolated Perfused Kidney (IPK) model was developed to take advantage of mouse genetic design capabilities for testing complex biological hypothesis regarding mechanisms of preservation injury in transplanted kidneys.

Methods: Mouse kidneys were recovered, preserved, and reperfused in-vitro with an acellular physiological crystalloid buffer containing hypo-physiological oncotic pressure.

Protective effects of ezrin on cold storage preservation injury in the pig kidney proximal tubular epithelial cell line (LLC-PK1).

Background: Renal damage caused by cold preservation and warm reperfusion has been well documented and involves tissue edema, cell swelling, ATP depletion, calcium toxicity, and oxidative stress. However, more common proximal mechanisms have not been identified, which may limit the development of effective clinical treatment strategies. Previous work indicates that many cytoskeletal structures are affected by cold preservation and reperfusion, including membrane-rich ezrin-associated complexes.

Cytoskeletal involvement in hypothermic renal preservation injury.

Background: Cytoskeletal degradation occurs in warm renal ischemia and reperfusion and during hypothermia. The purpose of this study was to determine cytoskeletal changes during cold storage preservation injury in renal tubules and to determine whether these changes contribute to the injury.

Methods: Isolated canine renal proximal tubules or their primary epithelial cultures were cold-stored in University of Wisconsin solution and reperfused in vitro to simulate renal cold storage preservation injury.

Hibernation confers resistance to intestinal ischemia-reperfusion injury.

The damaging effects of intestinal ischemia-reperfusion (I/R) on the gut and remote organs can be attenuated by subjecting the intestine to a prior, less severe I/R insult, a process known as preconditioning. Because intestines of hibernating ground squirrels experience repeated cycles of hypoperfusion and reperfusion, we examined whether hibernation serves as a model for natural preconditioning against I/R-induced injury. We induced intestinal I/R in either the entire gut or in isolated intestinal loops using rats, summer ground squirrels, and hibernating squirrels during natural interbout arousals (IBA; body temperature 37-39 degrees C).

Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals.

Background: In the rodent, ischemic preconditioning (IPC) has been shown to improve the tolerance of the liver to ischemia-reperfusion under normothermic or hypothermic conditions. The aim of the present study was to test this hypothesis in a dog model, which may be more relevant to the human.

Methods: Beagle dogs were used in two distinct animal models of hepatic warm ischemia and orthotopic liver transplantation (hypothermic ischemia).

UW solution for hypothermic machine perfusion of warm ischemic kidneys.

Background: Donation of kidneys from non-heart beating donors (NHBD) is increasingly being used to expand the donor pool. Warm ischemic injury of these kidneys suffered at harvest results in DGF at transplantation. In this study, we used hypothermic continuous machine perfusion preservation to mitigate this injury using two available solutions.

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype.

The success of liver grafts is currently limited by the length of time organs are cold preserved before transplant. Novel insights to improve viability of cold-stored organs may emerge from studies with animals that naturally experience low body temperatures (T(b)) for extended periods. In this study, we tested whether livers from hibernating ground squirrels tolerate cold ischemia-warm reperfusion (cold I/R) for longer times and with better quality than livers from rats or summer squirrels.

Brain death does not affect hepatic allograft function and survival after orthotopic transplantation in a canine model.

Background: Brain death has been shown to decrease graft function and survival in rodent models. The aim of this study was to evaluate how brain death affects graft viability in the donor and liver tolerance to cold preservation as assessed by survival in a canine transplant model.

Methods: Beagle dogs were used for the study.

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

Background: The ability to effectively utilize kidneys damaged by severe (2 hr) warm ischemia (WI) could provide increased numbers of kidneys for transplantation. The present study was designed to examine the effect of restoring renal metabolism after severe WI insult during ex vivo warm perfusion using an acellular technology. After warm perfusion for 18 hr, kidneys were reimplanted and evaluated for graft function.