Perfusion using oxygenated buffer containing prostaglandin E1 before cold preservation prevents warm ischemia-reperfusion injury in liver grafts from non-heart-beating donors.

We have previously reported that perfusion using warm oxygenated buffer before cold preservation (preperfusion) improved the viability of liver grafts from non-heart-beating donors. We demonstrated that adenosine triphosphate content was restored and apoptosis was reduced. The objective of the present study was to evaluate mitochondrial functions after this preperfusion and the effects of addition of prostaglandin E(1) (PGE(1)) to the preperfusion buffer. Preperfusion improved portal flow, bile production, and mitochondrial function, and reduced alanine aminotransferase levels in the perfusate. Addition of PGE(1) significantly increased bile production and suppressed alanine aminotransferase and tumor necrosis factor-α levels. PGE(1) minimized mitochondrial membrane damage and ischemic injury after liver graft reperfusion. Release of mitochondrial cytochrome c was suppressed by addition of PGE(1). In conclusion, perfusion using oxygenated buffer containing PGE(1) before cold preservation significantly prevented cellular damage, protected mitochondrial function, and suppressed the release of mitochondrial cytochrome c in livers undergoing warm ischemia-reperfusion injury. This method shows promise for reducing cellular damage in non-heart-beating donor liver grafts.

Signaling pathway on the effect of oxygenated warm perfusion prior to cold preservation of the liver grafts from non-heart-beating donors, and the additive effect of edaravone.

We have previously reported that oxygenated warm perfusion prior to cold preservation (preperfusion) improved the function and viability of liver grafts from non-heart-beating donors (NHBD) using an ex vivo perfusion model. In this study, we evaluated the signaling pathway underlying these effects as well as the additive effect of preperfusion administration of edaravone, a free radical scavenger. Preperfusion treatment suppressed activation of JNK, p38 MAPK, and ERK. The addition of edaravone provided an insignificant increase in bile production and a trend to a decrease in TUNEL-positive cells. Oxygenated perfusion prior to cold preservation improved the function and viability of the grafts from NHBD, which accompanied impairment of MAPK activation. Moreover, the addition of edaravone significantly enhanced the effects of preperfusion.

Management of living donor liver transplant patients using twice-daily 4-hour intravenous cyclosporine therapy.

Oral administration of cyclosporine (CsA) is the currently favored route in most liver transplant centers. From October 1998 to January 2008, 86 living donor liver transplantations (LDLTs) were performed in 85 patients (46 adults and 39 children) at our institution. Seventy-three patients received tacrolimus (Tac), and 12 intravenous CsA twice daily at a dose of 3 mg/kg/d as a 4-hour continuous infusion. Thirteen of 73 Tac-based patients were switched to CsA because of side effects. Five were switched to intravenous CsA because they were unable to take the drug orally because of severe Tac-related complications. The remaining eight patients switched to oral CsA. We evaluated patients (11 adults and three children), including 12 with induction therapy and two with conversion therapy within 2 weeks of LDLT. The patients were given a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d. Stable and adequate blood CsA concentrations were achieved by 4-hour intravenous CsA administration. Among several factors, only graft-to-recipient weight ratio (r = .743, P < .0001) showed significant correlations with initial blood CsA concentration. No adverse effects were observed after intravenous CsA. No patients developed biopsy-proven acute cellular rejection (ACR) during intravenous CsA administration, whereas two patients had histopathologically diagnosed episodes of ACR after conversion from intravenous to oral CsA. Our findings suggest that immediate administration of a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d is practical and effective for routine clinical use.

The effect of perfusion prior to cold preservation and addition of biliverdin on the liver graft from non-heart-beating donors.

AIM: Our aim was to improve the energy status and viability of a liver graft from a non-heart-beating donor (NHBD), we investigated the effects of perfusion prior to cold preservation and the addition of an antioxidant, biliverdin. METHODS: Rats were divided into five groups: group 1: without 30 minutes warm ischemia (WI) and cold preservation (control group); group 2 without WI and with 6 hours of cold preservation in UW solution (HBD group); group 3 with WI and cold preservation (NHBD group); group 4 with 30 minutes perfusion prior to cold preservation (PRE group); and group 5 with addition of biliverdin to precold preservation perfusion (BV group). Oxygenated Klebs-Henseleit solution was used as the perfusate prior to and after preservation. Portal flow and bile production during reperfusion, energy charge (EC), ATP level, GOT, and TNF-alpha were measured as well as a histological evaluation. RESULTS: Portal flow of the PRE and BV groups during 1 hour of reperfusion was higher than of that the NHBD group. Bile production of the PRE group was also higher than that of the NHBD group, but bile production in the BV group was comparable to the NHBD group. EC of the PRE group was higher than that of the NHBD group prior to and after reperfusion. The EC and ATP levels of the BV group after reperfusion were higher than those of the NHBD and PRE groups. The GOT and TNF-alpha were reduced in the BV group. CONCLUSIONS: Precold preservation perfusion improves the viability of grafts from NHBDs. Furthermore, biliverdin exerted an additive effect to ameliorate energy status.

Experience with recipient's superficial femoral vein as conduit for middle hepatic vein reconstruction in a right-lobe living donor liver transplant procedure.

Middle hepatic vein reconstruction during the right-lobe living donor liver transplant procedure has been recognized to be a significant factor. We initially reconstructed only a single middle hepatic vein orifice draining into segment 8. In cases where the right-lobe liver graft has several major middle hepatic vein tributaries, including veins draining segment 5 that are remote from the right hepatic vein orifice, a long and thick interposition conduit is necessary for reconstruction. Among 11 consecutive adult patients who received a right-lobe liver graft without a middle hepatic vein at our institution, 8 underwent reconstruction of all major middle hepatic vein tributaries using a vein graft from the recipient's superficial femoral vein. The remaining 3 patients had no major middle hepatic vein tributaries. Posttransplant-computed tomography imagings showed increased liver mass with a patent superficial femoral vein graft in 8 patients. In the absence of a venous system from a deceased donor, a recipient superficial femoral vein offers an excellent size match to maintain the venous outflow of middle hepatic vein tributaries. Reconstruction with recipient superficial femoral vein plays an important role in maximizing liver function and minimizing morbidity in the early posttransplant period.

Possible impact of treated wastewater discharge on incidence of antibiotic resistant bacteria in river water.

Escherichia coli and coliform group bacteria resistant to seven antibiotics were investigated in the Tama River, a typical urbanized river in Tokyo, Japan, and at a wastewater treatment plant located on the river. The percentages of antibiotic resistance in the wastewater effluent were, in most cases, higher than the percentages in the river water, which were observed increasing downstream. Since the possible increase in the percentages in the river was associated with treated wastewater discharges, it was concluded that the river, which is contaminated by treated wastewater with many kinds of pollutants, is also contaminated with antibiotic resistant coliform group bacteria and E. coli. The percentages of resistant bacteria in the wastewater treatment plant were mostly observed decreasing during the treatment process. It was also demonstrated that the percentages of resistance in raw sewage are significantly higher than those in the river water and that the wastewater treatment process investigated in this study works against most of resistant bacteria in sewage.

Low-frequency, weak extradural stimulation in the management of intractable pain.

Low-frequency (1.6-2.2 Hz) and weak-intensity electrical stimulation in the spinal extradural space produced complete to partial pain relief in a majority of patients (22 of 25) who suffered from intractable pain. Also it produced analgesia or hypoalgesia over a wide area of the body surface in 19 of the 25.

Management of intractable pain in adiposis dolorosa with intravenous administration of lidocaine.

Intractable pain in a patient with adiposis dolorosa (Dercum's disease) was treated by IV administration of lidocaine (200 to 400 mg). Relief was maximum 20 minutes after the end of drug infusion and persisted for over 10 hours. Toxicity was minimal. Slow EEG waves which appeared during drug administration disappeared within 20 minutes.

Interactions of human cord dorsum potential.

The slow positive wave (P2 wave) of the evoked spinal electrogram was recorded from the posterior epidural space in wakeful man, and studied by applying several modes of peripheral nerve stimulation. With graded stimulation the P2 wave amplitude rapidly reached the maximum at weaker stimulation than that required for the initially positive spikes (P1) and the preceding negative (N1) wave. The "second" component of the P2 appeared during stronger stimulation or during excitemenpt of the subjects. With prolonged repetitive stimulation the P2 wave increased its duration with several summits on the decaying phase. Two interactions were observed between the P2 waves produced by conditioning and testing stimulations in the same or different nerves: inhibition or occlusion by strong stimulation and faciliation by weak stimulation. Thus, the characteristic of the P2 wave in man was similar in part to that of the positive wave observed in decerebrate animals, and differnt in other ways presumably due to influences from supraspinal structures or species differences.