RESUMO
BACKGROUND: Due to the severe shortage of deceased donors, demand for living-donor liver transplantation (LDLT) has increased worldwide. Here, we compared POLYSOL, a recently developed low-viscosity preservation solution, and histidine-tryptophan-ketoglutarate (HTK) for cold storage of partial liver graft in this study. METHODS: Partial liver transplantations with 30% of the native liver were performed in Lewis rats. The graft livers were flushed with either HTK or POLYSOL (n = 25, respectively) and stored in the respective solution for 3 h at 5°C. Graft function was evaluated regarding ischemia-reperfusion injury and regeneration at 1, 3, 24, and 168 h after reperfusion. RESULTS: POLYSOL preservation resulted in improvement of portal venous flow (HTK versus POLYSOL; mean ± SEM: 16.8 ± 2.2 versus 21.6 ± 2.1 mL/min; P = 0.005), microcirculation (383 ± 63 versus 532 ± 64 Flux; P = 0.045), ALT (310.2 ± 56.1 versus 181.8 ± 17.0 IU/L; P = 0.0262), LDH (4052.4 ± 764.4 versus 2494.1 ± 410.0 IU/L; P = 0.0215), total bilirubin (21.6 ± 14.2 versus 4.0 ± 0.6 IU/L; P = 0.0236), malondialdehyde (100.0 ± 4.3 versus 69.2 ± 4.0 nmol/mL; P = 0.0015), as well histologic findings at 24 h. Liver regeneration was improved in POLYSOL with regards to liver weight (4.0 ± 0.2 versus 4.3 ± 0.3 g; P = 0.038) and Ki-67 labeling index (9.67 ± 2.17 versus 1.10 ± 0.14%; P < 0.0001) at 24 h with higher up-regulation of portal VEGF (31.55 ± 5.78 versus 91.94 ± 9.27 pg/mL; P = 0.0052). CONCLUSIONS: This study showed that POLYSOL improves microcirculation and thus improves the preservation quality of partial liver transplantation.
Assuntos
Transplante de Fígado/fisiologia , Fígado/irrigação sanguínea , Fígado/fisiologia , Soluções para Preservação de Órgãos/uso terapêutico , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/metabolismo , Animais , Bilirrubina/metabolismo , Temperatura Baixa , Glucose/uso terapêutico , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Manitol/uso terapêutico , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Modelos Animais , Soluções para Preservação de Órgãos/farmacologia , Cloreto de Potássio/uso terapêutico , Procaína/uso terapêutico , Ratos , Ratos Endogâmicos Lew , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Traumatismo por Reperfusão/fisiopatologiaRESUMO
AIM: To evaluate the potential of Polysol, a newly developed preservation solution, in cold storage of small bowel grafts, compared with the current standards, University of Wisconsin solution (UW), Celsior and histidine-tryptophan-ketoglutarate solution (HTK). METHODS: Male Wistar rats were used as donors. Small bowels were retrieved, flushed and then stored in the respective 4 solutions for 18 h at 4 centigrade. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37 centigrade for 30 min in all 4 groups. RESULTS: Polysol preservation exhibited the highest tissue ATP concentration and the lowest release of LDH. Malondialdehyde, an index for tissue lipid peroxidation, was also the lowest in Polysol. Tissue oxygen consumption was significantly higher in Polysol than in the others. Of interest, UW-storage promoted 10-fold higher apoptosis than in the others. Moreover, electron microscopy revealed that the mucosal villi/micro-villi formation and the cell organelles, including mitochondria, were both significantly better preserved in Polysol, while deleterious alterations were apparent in the others, most notably in UW. Although Celsior and HTK exhibited the better trend of results than UW in some parameters, but could not reach the over-all superiority to UW. CONCLUSION: Cold storage using Polysol resulted in significantly better integrity and function of small bowel grafts than UW. Hence, Polysol may be a novel alternative for the small bowel preservation.
Assuntos
Intestino Delgado/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Coleta de Tecidos e Órgãos , Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Alopurinol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Temperatura Baixa , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Estudos de Viabilidade , Glucose/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Histidina/farmacologia , Insulina/farmacologia , Intestino Delgado/enzimologia , Intestino Delgado/metabolismo , Intestino Delgado/transplante , Intestino Delgado/ultraestrutura , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Manitol/farmacologia , Microscopia Eletrônica , Microvilosidades/efeitos dos fármacos , Microvilosidades/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Consumo de Oxigênio/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Rafinose/farmacologia , Ratos , Ratos WistarRESUMO
Chronic shortage of donor organs has led to acceptance of steatotic livers as grafts, although there is a higher risk of primary graft dysfunction. We herein report the beneficial impact of Polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Dietary hepatic steatosis was induced in Wistar rats by 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. Fatty livers were retrieved, flushed and then stored at 4 degrees C for 24 hours with either HTK or Polysol. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37 degrees C for 45 minutes in both groups. Polysol preservation resulted in significant reductions of not only parenchymal (AST (IU/L); 6728+/-824 in HTK vs. 3107+/-718 in Polysol; P < 0.001) but also mitochondrial (GLDH (IU/L); 3189+/-773 vs. 1282+/-365; P < 0.01) enzyme release throughout reperfusion. Moreover, PVP (16.9+/-2.7 vs. 7.8+/-1.5 mmHg; P < 0.05), hepatic O2 consumption (0.291+/-0.047 vs. 1.056+/-0.053 micromol/g liver/min; P < 0.001), tissue ATP content (0.695+/-0.086 vs. 1.340+/-0.157 micromol/g dry-liver; P < 0.005), bile production (0.79+/-0.11 vs. 4.08+/-0.66 microL/g liver/45-min; P < 0.001), malondialdehyde into the perfusate (1.922+/-0.198 vs. 0.573+/-0.094 nmol/L; P < 0.0001) and wet/dry-weight ratio of the liver tissues (5.20+/-0.31 vs. 3.85+/-0.15; P < 0.005) were all better preserved by Polysol. In line with these benefits, electron microscopy revealed that Polysol preservation substantially suppressed deleterious mitochondrial alterations in steatotic livers. In conclusion, cold storage using Polysol resulted in significantly better integrity and function of steatotic livers. Polysol, therefore, may be a new alternative especially for "marginal" organs.