The role of glycine in hepatic ischemia-reperfusion injury.

Glycine is a non-essential amino acid which is cheap, easily available and relatively non-toxic. It is composed of a single carbon attached to an amino and a carboxyl group, with a molecular weight of 75. It is involved in the production of bile, nucleic acids, porphyrins and creatine phosphate. It is part of the normal human diet and is used clinically, as an irrigant solution in urological and gynaecological procedures. Glycine has broad spectrum anti-inflammatory, cytoprotective and immunomodulatory properties whose therapeutic role has largely been un-investigated. Since the demonstration of its cytoprotective effect on hypoxic cultured renal tubule cells, further research has established its mechanism of anti-inflammatory action, which depends on stimulation of glycine sensitive chloride channel receptors on the cell membrane. The mechanism of non-specific cytoprotective effect which is present even in chloride and calcium free media is not clear. However glycine is currently being used experimentally, in human liver transplant recipients and has been shown to be beneficial in animal models of ischemia-reperfusion injury (IRI) in liver and several other organs. This review addresses the properties of glycine, its mechanism of action and its role in modulating IRI with special reference to the liver, with the aim of stimulating translational research into the potential role of glycine as a pharmaceutical agent.

Near-infrared spectroscopic assessment of mitochondrial oxygenation status--comparison during normothermic extracorporeal liver perfusion by buffer only or buffer fortified with washed red blood cells: an experimental study.

BACKGROUND: Use of marginal and non-heart-beating donors leads to an increased incidence of complications after clinical liver transplantation. Normothermic extracorporeal liver perfusion (NELP) may allow resuscitation and evaluation of such organs. Despite recent success in long-term liver preservation by NELP, no methods of organ evaluation have been defined. Mitochondrial cytochrome oxidase (Cyt Ox) levels reflect oxygen and substrate delivery, and hence ATP production at the cellular level. This study used near-infrared spectroscopy (NIRS) to measure Cyt Ox levels during NELP. METHODS: Livers retrieved from New Zealand white rabbits were immediately perfused in an extracorporeal circuit with oxygenated buffer (group A, n = 4) or red blood cell (RBC)-fortified buffer (group B, n = 4). Perfusion was continued for 3 hours at 37 degrees C pH 7.4, and perfusate was gassed with 95%O2/5%CO2 at 1 liter per minute. Cyt Ox levels were monitored continuously by NIRS and bile output was measured. RESULTS: Cyt Ox was reduced at the start of perfusion in both groups, but even more rapidly in the buffer-perfused group. After initial deterioration, Cyt Ox levels improved significantly (P < .05) with perfusion in the RBG-perfused group, but remained impaired in the buffer group 5.74 +/- 1.51 Deltamicromol/L and -25.77 +/- 21.94 Deltamicromol/L for groups B and A, respectively, at 180 minutes. Differences in bile output were not significant (19.33 +/- 9.50 and 25.00 +/- 16.81 micromol/min/100 g for groups B and A respectively). CONCLUSIONS: Cyt Ox levels may offer better viability markers than bile output. NIRS is a practical method to measure tissue oxygenation, and RBC-based perfusion provided better oxygenation during NELP.

A comparison of bile composition from heart-beating and non-heart-beating rabbit organ donors during normothermic extracorporeal liver perfusion: experimental evaluation using proton magnetic resonance spectroscopy.

BACKGROUND: Organs retrieved from marginal and non-heart-beating donors (NHBDs) have sustained variable degrees of preretrieval damage that result in an increased incidence of complications. Normothermic extracorporeal liver perfusion (NELP) provides an opportunity to evaluate and resuscitate such organs. The aim of this study was to identify markers of ischemic injury in bile during perfusion of livers from heart-beating donors (HBDs) and NHBDs. METHODS: Livers were retrieved from New Zealand white rabbits. The HBD group (n=4) had no in situ warm ischemia before retrieval and the NHBD group (n=4), 45 minutes of in situ warm ischemia before liver retrieval. After 40 minutes of postretrieval cold ischemia, all livers were dual vessel reperfused, normothermically with oxygenated buffer solution supplemented with rabbit red blood cells, for 6 hours. Bile was collected and examined with 1HMRS. RESULTS: Perfusion bile from HBD group showed an increased concentration of bile acids, lactate, glucose, and phosphatidylcholine, but a decreased concentration of acetate as compared to retrieval bile. This trend was further enhanced in NHBD group. The mean +/- SD (in micromol/L) were bile acids (10.48 +/- 2.8 vs 26.05 +/- 12.1 vs 44.5 +/- 44.5), lactate (10.66 +/- 4.5 vs 14.66 +/- 5.2 vs 13.22 +/- 1.8), glucose (5.37 +/- 2 vs 21.2 +/- 5.0 vs 29.09 +/- 15.3), phosphatidylcholine (0.21 +/- 0.02 vs 5.57 +/- 1.7 vs 6.42 +/- 0.3), and acetate (1.8 +/- 0.5 vs 0.39 +/- 0.1 vs 0.38 +/- 0.09) for retrieval bile, HBD perfusion bile, and NHBD perfusion bile, respectively. One animal from each group did not produce any bile during perfusion. CONCLUSIONS: 1HMRS of biliary constituents revealed differences with the type of ischemia. These indices may be potential markers of the extent of warm ischemic injury and the functional activity of an extracorporeally perfused liver.