J Brassil

Machine perfusion of the liver: past, present and future.

Purpose of reviewThis review considers the potential of machine perfusion to preserve livers for clinical transplantation, including steatotic or ischaemically damaged grafts and aims to go over the most significant achievements in liver machine perfusion over the last year. To reach acceptance in liver preservation, machine perfusion will need to improve outcomes compared with simple cold storage (SCS), provide objective measures of graft viability, and resuscitate less-than-ideal grafts before transplantation. Recent findingsCurrent machine perfusion protocols comprise both hypothermic (HMP) and normothermic (NMP) approaches. HMP increases energy stores compared to SCS, and NMP shows additional resuscitative potential. Dutkowski transplanted ischaemically damaged pig livers after HMP following SCS, which avoided graft failure observed after SCS alone. Guarrera performed 20 clinical transplants after 4–7 h HMP. Friend has performed porcine transplantations after NMP of 4–20 h and univocally demonstrated the significant resuscitative effects on ischaemically damaged grafts otherwise destined to fail. Whereas NMP promises resuscitative effects, it demands challenging, near-physiologic conditions. Subnormothermic perfusion is being tested as a promising medium in between. SummaryDespite recent substantial improvements, liver preservation by machine perfusion remains limited and in contrast to the global revival of kidney machine perfusion. However, liver machine perfusion may be close to returning to clinical practice if it has not already done so. History shows that superiority alone does not guarantee immediate clinical use. Further clear-cut benefits of machine perfusion such as viability assessment will have to be accompanied by usability and human factors, and innovative and improved perfusion solutions applied in novel perfusion protocols.

Discriminate Liver Warm Ischemic Injury During Hypothermic Machine Perfusion by Proton Magnetic Resonance Spectroscopy: A Study in a Porcine Model

OBJECTIVE Proton magnetic resonance spectroscopy ((1)H MRS) is a technique to identify and quantify the composition of biofluids. Hypothermic machine perfusion (HMP) is an organ preservation method that has the potential to evaluate organ viability prior to transplantation by analyzing the composition of the perfusate. The aim of this study was to use (1)H MRS to examine the perfusate during HMP of porcine livers exposed to warm ischemia (WI) and to identify potential biomarkers of liver viability. MATERIALS AND METHODS Porcine livers underwent 4 hours of HMP using kidney perfusion solution-1 (KPS-1) as perfusate after exposure to in situ WI of 0 (n = 6) or 2 hours (n = 5). Samples of the perfusate were taken at the start/end of HMP. Lactate and aspartate aminotransferase (AST) in the samples were measured biochemically as surrogates of the WI-induced damage. MRS acquisition was conducted on a 9.4 Tesla (400 MHz) high-resolution system. RESULTS AST increased significantly during 4 hours of HMP within groups (P < .02) and discriminated WI injury significantly from the start to the end of HMP (P < .03). (1)H MRS showed significantly elevated signal intensity of lactate, alanine, and histidine during HMP within both groups (P < .02). Furthermore, alanine and histidine were significantly higher in the WI group than in the control group at the end of HMP (P = .011 and P = .038, respectively). CONCLUSION AST, alanine, and histidine in HMP perfusate discriminated WI injury on porcine liver grafts and might be potential biomarkers of liver viability.

Air embolism during liver procurement: an underestimated phenomenon? A pilot experimental study.

BACKGROUND Intrahepatic air embolism can occur during liver transplantation, jeopardizing the posttransplant outcome. Until now, the role of the procurement in the origin of intrahepatic air remains unclear; it might be underestimated. In this pilot study using magnetic resonance imaging (MRI), we observed a substantial amount of air trapped in porcine livers during multiorgan procurement. We quantified the amount of air, examining whether it could be reduced by avoiding direct contact of air with the lumen of the hepatic vasculature during procurement and back-table preparation. METHODS Five livers (control group) were procured according to standard techniques for comparison with 6 livers (modified group) where air could not enter into the livers due to clamping of the vasculature. MRI was performed during continuous machine perfusion (MP) preservation there after. We counted the number of black signal voids on T(2)*-weighted images, which were indicative of air bubbles within the hepatic contour. Additionally, an MRI contrast agent (gadolinium-diethylene triamine pentaacetic acid [Gd-DTPA]) was injected into the hepatic artery and circulated by MP. Insufficiently perfused areas with less contrast enhancement were analyzed quantitatively in T(1)-weighted images and expressed as the percentage of total liver volume. RESULTS The images of the control livers showed more air bubbles compared with the modified group (45 ± 27 vs 6 ± 3; P = .004). The percentage of insufficiently perfused areas was higher among the control compared with the modified group (28.0 ± 15.8% vs 2.6 ± 4.6%; P = .047) on first-pass postcontrast T(1)-weighted images. After recirculating the contrast agent, insufficiently perfused areas showed similar localizations and contours within every liver. CONCLUSION These data suggested that a substantial amount of air enters into the hepatic microcirculation through direct contact of air with the hepatic vasculature during standard procurement and back-table preparation. Avoiding opening the hepatic vessels to air substantially reduced this phenomenon.