Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model

ABSTRACT Purpose: To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia. Materials and Methods: Male rats were allocated into 4 groups: sham (S), sham quercetin (SQ), ischemia (I), and ischemia quercetin (IQ). Groups SQ and IQ received quercetin (50mg/kg) before and after surgery. Groups I and IQ had their left renal vessels clamped for 60 minutes. All animals were euthanized four weeks after the procedure, and serum urea and creatinine levels were measured. Renal weight and volume, cortex-non-cortex area ratio (C-NC), cortical volume (CV), glomerular volumetric density (Vv[glom]), volume-weighted glomerular volume (VWGV) and number of glomeruli per kidney (N[glom]) were evaluated by stereological methods. Results were considered statistically significant when p <0.05. Results: Serum urea levels in group I increased by 10.4% in relation to group S, but no differences were observed among the other groups. The C-NC of group I was lower than those of all other groups, and group IQ had similar results to sham groups. The Vv[glom] and N[glom] of group I were lower than those of group S (33.7% and 28.3%, respectively) and group IQ had no significant difference compared to the S group. Conclusions: Quercetin was effective as a nephroprotective agent in preventing the glomerular loss observed when the kidney was subjected to warm ischemia. This suggests that this flavonoid may be used preventively in kidney surgery, when warm ischemia is necessary, such as partial nephrectomy.

Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model.

PURPOSE: To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia. MATERIALS AND METHODS: Male rats were allocated into 4 groups: sham (S), sham quercetin (SQ), ischemia (I), and ischemia quercetin (IQ). Groups SQ and IQ received quercetin (50mg/kg) before and after surgery. Groups I and IQ had their left renal vessels clamped for 60 minutes. All animals were euthanized four weeks after the procedure, and serum urea and creatinine levels were measured. Renal weight and volume, cortex-non-cortex area ratio (C-NC), cortical volume (CV), glomerular volumetric density (Vv[glom]), volume-weighted glomerular volume (VWGV) and number of glomeruli per kidney (N[glom]) were evaluated by stereological methods. Results were considered statistically significant when p < 0.05. RESULTS: Serum urea levels in group I increased by 10.4% in relation to group S, but no differences were observed among the other groups. The C-NC of group I was lower than those of all other groups, and group IQ had similar results to sham groups. The Vv[glom] and N[glom] of group I were lower than those of group S (33.7% and 28.3%, respectively) and group IQ had no significant difference compared to the S group. CONCLUSIONS: Quercetin was effective as a nephroprotective agent in preventing the glomerular loss observed when the kidney was subjected to warm ischemia. This suggests that this flavonoid may be used preventively in kidney surgery, when warm ischemia is necessary, such as partial nephrectomy.

Effectiveness and safety of partial nephrectomy-no ischemia vs. warm ischemia: Systematic review and meta-analysis.

PURPOSE: This study aimed to determine the effectiveness and safety of partial nephrectomy (PN) without ischemia compared with PN with warm ischemia for reducing the deterioration in renal function in patients with cT1 renal tumors. MATERIALS AND METHODS: We conducted a systematic review that included patients over 18 years of age who underwent PN with or without warm ischemia for cT1 renal tumors. The primary outcome was impaired renal function. A search strategy was performed in MEDLINE, EMBASE, LILACS, CENTRAL, the article reference lists, and the unpublished literature to reach saturation of the information. We assessed the risk of bias with the methodological index for nonrandomized studies (MINORS) tool, and we performed a meta-analysis according to the type of variable. RESULTS: We found a total of 5,682 articles, of which 14 met the inclusion criteria. Seven studies evaluated renal function, identifying a difference in means (MD) of 3.50 (95% confidence interval [CI], 1.16 to 5.83), favoring no ischemia. We did not find any significant differences regarding intraoperative bleeding or operative time (MD, 55 mL; 95% CI, -33.16 to 144.08; and MD, 1.87; 95% CI, -20.47 to 24.21; respectively). CONCLUSIONS: In this study, PN without ischemia showed a decrease in deterioration of the estimated glomerular filtration rate compared with warm ischemia.

Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience.

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. STUDY DESIGN: Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada between 1995 and 2016. RESULTS: Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P = .02). Adolescents aged 11-17 years (OR, 0.53; P = .03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90 days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). CONCLUSIONS: These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

Oncological and functional outcomes of open versus laparoscopic partial nephrectomy in T1b tumors: A single-center analysis

ABSTRACT Purpose: This study aims to evaluate the oncological and functional results of open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) at the T1b clinical stage, which constitutes 25% of renal cell carcinomas (RCC) at diagnosis. Materials and Methods: The characteristics of 63 patients with stage T1b solitary tumor who underwent OPN (41) or LPN (22) were compared. The survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting disease-free survival. Potential predictive factors, which might affect the postoperative glomerular filtration rate (GFR), were evaluated using multivariate linear regression analysis. Results: No differences were observed between OPN and LPN groups regarding patient and tumor characteristics. Although the warm ischemia time, intraoperative estimated blood loss, and operation duration were higher in the LPN group, no differences were noted between the two techniques regarding complication rates (p<0.001, p=0.023, p≤0.001, and p=0.190, respectively). The median hospitalization time was shorter in the LPN group than that in the OPN group (4 and 5 days, respectively), with less severe complications. No intergroup differences were observed regarding cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS). The evaluation of the factors affecting DFS showed that age was an effective parameter (RR = 1.112, 95% CI: 1.010-8.254), but the surgical technique was not. Conclusion: No differences were observed between OPN and LPN techniques between oncological and functional outcomes in patients with clinical stage T1b RCC.

Histomorphometric and biochemical data of rat kidney submitted to warm ischemia associated with resveratrol treatment.

The data presented here come from the article "Histomorphometric evaluation of the rat kidney submitted to warm ischemia and the protective effect of resveratrol" [1]. Rats of Wistar lineage (n = 39; 9 weeks of age) were obtained and apportioned into 4 groups at random. Both groups Sham (S) and Sham Resveratrol (SR) were submitted to open laparotomy and dissection of the left renal pedicle, the same as groups Ischemia (I) and Ischemia Resveratrol (IR), being the last two also submitted to 1 h left warm renal ischemia. SR and IR were treated with 30 mg/kg of resveratrol intraperitoneally 1 h before the surgical procedure, while S and I received saline injections. Rats were killed a month after surgery by anesthetic overdose. A blood sample was collected by cardiac puncture for determination of serum urea and creatinine serum by biochemical analysis at automated enzymatic method. Kidneys were weighted, Sherle´s method was used for measurement of their volume and then both were fixated in buffered formalin for 48 h. Cortex-non-cortex areas ratio (C-NC) was assessed by Cavalieri's method using a stereoscope. The product of multiplying the renal volume by the C-NC is the cortical volume (CV). Left kidneys fragments were processed for histology resulting in slides that were stained with haematoxylin and eosin. For histomorphometric analyses, 25 random cortical fields were photographed at 200x magnification using a camera attached to a light microscope. The estimation of glomerular volumetric density (Vv [Glom]), indication of proportional volume occupied by glomeruli in the cortex, was performed by the point-counting method. The point-sampled intercepts method was used to estimate the volume-weighted mean glomerular volume (VWGV). Total number of glomeruli per kidney (N [Glom]) estimation was achieved through the formula CVxVv [Glom]/VWGV. All the data were tabulated in spreadsheets. The quantitative results were compared by one-way ANOVA with Tukey's post-test using GraphPad Prism software. All results were considered significant when the value of p <0.05.

Oncological and functional outcomes of open versus laparoscopic partial nephrectomy in T1b tumors: A single-center analysis.

PURPOSE: This study aims to evaluate the oncological and functional results of open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) at the T1b clinical stage, which constitutes 25% of renal cell carcinomas (RCC) at diagnosis. MATERIALS AND METHODS: The characteristics of 63 patients with stage T1b solitary tumor who underwent OPN (41) or LPN (22) were compared. The survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting disease-free survival. Potential predictive factors, which might affect the postoperative glomerular filtration rate (GFR), were evaluated using multivariate linear regression analysis. RESULTS: No differences were observed between OPN and LPN groups regarding patient and tumor characteristics. Although the warm ischemia time, intraoperative estimated blood loss, and operation duration were higher in the LPN group, no differences were noted between the two techniques regarding complication rates (p<0.001, p=0.023, p≤0.001, and p=0.190, respectively). The median hospitalization time was shorter in the LPN group than that in the OPN group (4 and 5 days, respectively), with less severe complications. No intergroup differences were observed regarding cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS). The evaluation of the factors affecting DFS showed that age was an effective parameter (RR = 1.112, 95% CI: 1.010-8.254), but the surgical technique was not. CONCLUSION: No differences were observed between OPN and LPN techniques between oncological and functional outcomes in patients with clinical stage T1b RCC.

Histomorphometric evaluation of the rat kidney submitted to warm ischemia and the protective effect of resveratrol.

BACKGROUND: The objective of this study is to quantitatively evaluate the protective effects of resveratrol for using during renal warm ischemia. METHODS: Rats were allocated into 4 groups: Sham, Sham Resveratrol, Ischemia, Ischemia Resveratrol. Sham Resveratrol and Ischemia Resveratrol received resveratrol before surgery. Ischemia and Ischemia Resveratrol had renal vessels clamped. Animals were euthanized four weeks after. Serum urea and creatinine were measured. Renal weight and volume, cortex-non-cortex areas ratio, cortical volume, glomerular volumetric density, volume-weighted mean glomerular volume and number of glomeruli per kidney were evaluated. RESULTS: Serum urea in Ischemia increased by 10.4% compared to Sham and no differences were observed among Ischemia Resveratrol and sham groups. The glomerular volumetric density and number of glomeruli of Ischemia were lower than Sham but Ischemia Resveratrol had no difference compared to sham groups. CONCLUSIONS: Preoperative administration of resveratrol has renoprotective effects, preventing the glomerular number reduction observed in warm ischemia.

Mannitol reduces nephron loss after warm renal ischemia in a porcine model.

BACKGROUND: Mannitol has been employed to ameliorate renal warm ischemia damage during partial nephrectomy, however, there is limited scientific evidence to support the use of mannitol during partial nephrectomy. The objective of the present study was to investigate the glomerular number after renal warm ischemia, with and without the use of mannitol in a Pig Model. METHODS: Twenty-four male pigs were assigned into three groups. Eight animals were allocated to the sham group that was subjected to laparoscopic dissection of the left renal hilum, without renal ischemia. Eight animals were allocated to the ischemia group that had the left renal hilum clamped for 30 min through laparoscopic access. Eight animals received mannitol (250 mg/kg) before the occlusion of renal hilum for 30 min. The kidneys were collected after the euthanasia of the pigs 21 days post surgery. The right kidney was utilized as a self-control for each animal. Serum creatinine, urea levels, the weight and volume of the kidneys were measured. Glomerular volumetric density, volume-weighted glomerular volume, and cortical volume were quantified through stereological methods and employed to determine the number of nephrons per kidney. Student's t test and ANOVA were used for statistical analysis. RESULTS: In the ischemia group, the left kidney recorded a reduction of 24.6% (290, 000 glomeruli) in the number of glomeruli in comparison to the right kidney. Kidneys subjected to ischemia also displayed decreased weight and volume in comparison to the sham and mannitol groups. No difference was observed between the left and right kidneys from the sham and mannitol groups. Further, no distinction in serum creatinine and urea among the groups was observed. CONCLUSION: The use of mannitol significantly reduces nephron loss during warm ischemia in pigs.

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

Abstract Purpose: To investigate the glomerular number after different warm ischemia times. Methods: Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Results: Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. Conclusions: About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

Purpose: To investigate the glomerular number after different warm ischemia times. Methods: Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Results: Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. Conclusions: About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.(AU)

Glomerular Morphology and Renal Function after Warm Ischemia by Main Artery or Selective Clamping in a Porcine Model.

OBJECTIVE: The study aimed to evaluate the ischemic and non-ischemic areas after selective arterial occlusion by using stereological analysis of glomeruli, and to compare them with main arterial clamping and sham-operated animals. MATERIALS AND METHODS: Twenty-four male pigs were used in the study. The animals were divided into 3 groups with 8 animals in each as follows: group sham, submitted to laparoscopic dissection of the renal pedicle but not submitted to ischemia; group arterial (A), submitted to left renal artery clamping; and group selective (S), submitted to left renal artery caudal branch occlusion. Groups A and S underwent 30 min of warm ischemia. Left and right kidneys were collected after 21 days and renal fragments were processed for stereological evaluation. Glomerular volume density (Vv[glom]), mean glomerular volume (MGV), and glomerular density were measured. Serum creatinine and urea were assessed preoperatively, 10 days after surgery, and before euthanasia. RESULTS: There was no significant difference among groups with regard to renal function. Renal weight and volume were similar among groups. Also, no difference was observed between the groups with regard to Vv[glom], MGV, and glomerular density, both when compared to its right control or when left kidneys were compared. CONCLUSIONS: Selective arterial clamping technique was neither superior nor inferior to main artery clamping.

Glomerular Loss After Renal Radiofrequency Ablation Are Comparable to 30 Minutes of Warm Ischemia.

PURPOSE: To compare, with stereological methods, the glomerular loss in kidneys submitted to radiofrequency ablation (RFA) or warm ischemia. MATERIALS AND METHODS: Twenty-six male pigs were divided into three groups. Eight animals were allocated in the sham group, which was submitted to laparoscopic dissection of the left renal hilum, without renal ischemia. Eight animals were allocated in the ischemia group, which had the left renal hilum clamped for 30 minutes under laparoscopic access. Ten animals were submitted to RFA of the left kidney lower pole, under laparoscopic visualization. Animals were euthanized 21 days after surgery, when kidneys were collected. Fragments of the upper pole of the left kidney were processed for morphometric analysis. Right kidney was used as self-controls for each animal. Glomerular volumetric density (Vv[glom]); volume-weighted glomerular volume (VWGV); and glomerular density were quantified by stereological methods and compared by Student's t-test and one-way-analysis of variance with Dunnett's post-test. RESULTS: Three animals in the RFA group developed postoperative complications (Urinoma/Hydronephrosis) and were excluded from the analysis. No difference was found among the kidneys submitted to RFA and warm ischemia for all parameters. However, these kidneys showed lower Vv[glom] and glomerular density when compared to its self-controls (right kidneys), and when compared to sham-operated animals (p < 0.05). No difference was observed in regards to VWGV among the groups. CONCLUSION: RFA in pigs determines a significant reduction of glomerular density in the remaining parenchyma. This alteration was comparable to that observed in kidneys submitted to 30 minutes of warm ischemia.

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model

PURPOSE:To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model.METHODS:Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ.RESULTS:Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A.CONCLUSIONS:Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.(AU)

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model

ABSTRACT PURPOSE: To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. METHODS: Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. RESULTS: Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. CONCLUSIONS: Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

Kidney ischemia and reperfunsion syndrome: effect of lidocaine and local postconditioning / Síndrome de isquemia e reperfussão renal: efeito da lidocaína e do pós-condicionamento local

ABSTRACT Objective: to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. Methods: we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. Results: The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Conclusion: Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning.

RESUMO Objetivo: avaliar os efeitos do bloqueio da regulação do tônus vascular por meio do uso da lidocaína na técnica de pós-condicionamento isquêmico na síndrome de isquemia e reperfusão renal em ratos. Métodos: trinta e cinco ratos foram randomizados em sete grupos de cinco animais: Grupo 1- Controle; Grupo 2- Isquemia e Reperfusão; Grupo 3- Isquemia, Reperfusão e Solução Salina; Grupo 4- Pós-condicionamento Isquêmico; Grupo 5- Pós-condicionamento Isquêmico e Solução Salina; Grupo 6- Lidocaína; Grupo 7- Pós-condicionamento Isquêmico e lidocaína. Com exceção do grupo controle, todos os demais foram submetidos à isquemia renal de 30 minutos. Nos grupos de pós-condicionamento, foi realizado o ciclo de isquemia e reperfusão de cinco minutos cada, aplicado logo após a isquemia principal. Nos grupos salina e lidocaína foram instiladas as substâncias numa taxa de duas gotas por minuto. Para comparar os grupos, foram dosados os níveis séricos de ureia e creatinina e análise histopatológica renal. Resultados: os grupos pós-condicionamento e pós-condicionamento + lidocaína apresentaram uma redução nos valores de ureia e creatinina. O grupo lidocaína apresentou apenas uma redução nos valores de creatinina. Na análise histopatológica, apenas os grupos submetidos ao pós-condicionamento isquêmico apresentaram redução do grau de necrose tubular. Conclusão: a lidocaína não bloqueou os efeitos do pós-condicionamento na síndrome de isquemia e reperfusão renal, mas conferiu melhor na proteção glomerular quando aplicada em conjunto com o pós-condicionamento isquêmico.

Improving outcomes in DCDD liver transplantation: there can only be strength in numbers.

In the United States, liver transplantation using donation after circulatory determination of death (DCDD) donors is challenged by persistently inferior graft survival compared with donation after neurological death (DND), along with declining rates of liver transplantation relative to the total number of DCDD donors. Advances in adult-to-adult living donor liver transplantation graft survival temporally related to the Adult-to-Adult Living Donor Liver Transplantation Cohort Study consortium suggest that a similarly focused collaborative effort may serve to stimulate evolution within DCDD liver transplantation. Without a multi-center consortium to support innovative trials, the current state of DCDD liver transplantation is unlikely to progress.

Efeito protetor do per-condicionamento isquêmico remoto nas lesões da síndrome de isquemia e reperfusão renal em ratos / Protective effect of remote ischemic per-conditioning in the ischemia and reperfusion-induce renal injury in rats

OBJETIVO: Avaliar o efeito protetor do per-condicionamento isquêmico remoto nas lesões de isquemia e reperfusão renal induzida. MÉTODOS: Quinze ratos (Rattus Novergicus) foram randomizados em três grupos (n=5): Grupo Normalidade (GN), Grupo Controle - Isquemia e Reperfusão (GIR) e Grupo Per-condicionamento isquêmico remoto (GPER). Com exceção do grupo GN, todos os demais foram submetidos à isquemia renal de 30 minutos. No grupo GPER, foi realizado o per-condicionamento isquêmico remoto, constituído de três ciclos de isquemia e reperfusão de cinco minutos cada aplicado, durante o período de isquemia, no membro posterior esquerdo dos ratos, por meio de torniquete. Para quantificar as lesões, foram dosados os níveis séricos de ureia e creatinina, bem como, analisada a histopatologia renal. RESULTADOS: O grupo GPER apresentou-se com melhores níveis de ureia (83,74 ± 14,58%) e creatinina (0,72 ± 26,14%) quando comparado ao grupo GIR, se aproximando do grupo GN. Na histopatologia, os menores níveis de degeneração hidrópica e congestão medular foram encontrados no grupo GPER. CONCLUSÃO: O per-condicionamento isquêmico remoto apresentou importante efeito protetor na lesão de isquemia e reperfusão renal.

OBJECTIVE: To evaluate the protective effect of remote ischemic per-conditioning in ischemia and reperfusion-induced renal injuiry. METHODS: Fifteen rats (Rattus norvegicus) were randomized into three groups (n = 5): Group Normality (GN), Control Ischemia and Reperfusion (GIR) and Group remote ischemic per-conditioning (GPER). With the exception of the GN group, all others underwent renal ischemia for 30 minutes. In group GPER we performed the ischemic remote per-conditioning, consisting of three cycles of ischemia and reperfusion applied every five minutes during the ischemic period, to the left hindlimb of the rats by means of a tourniquet. To quantify the lesions we measured serum levels of creatinine and urea, as well as analyzed renal histopathology. RESULTS: The GPER group presented with better levels of urea (83.74 ± 14.58%) and creatinine (0.72 ± 26.14%) when compared to GIR group, approaching the GN group. Histopathologically, the lower levels of medullary congestion and hydropic degeneration were found in group GPER. CONCLUSION: The remote ischemic per-conditioning had a significant protective effect on renal ischemia and reperfusion.

L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury / A L-arginina durante a fase isquêmica protege o fígado das lesões de isquemia e reperfusão

PURPOSE: To investigate the effects of intravenous L-arginine (LG) infusion on liver morphology, function and proinflammatory response of cytokines during the early phase of ischemia-reperfusion injury (IRI). METHODS: Thirty rabbits were subjected to 60 minutes of hepatic ischemia and 120 minutes of reperfusion. An intravenous injection of saline or L-arginine was administered five minutes before the ischemia and five minutes before initiating the reperfusion and at the 55th and 115th minutes after the ischemia. Samples were collected for histological analysis of the liver and measurements of the serum AST, ALT and LDH and the cytokines IL-6 and TNF-alpha. RESULTS: It was observed a significant reduction of sinusoidal congestion, cytoplasmic vacuolization, infiltration of polymorphonuclear leukocyte, nuclear pyknosis, necrosis and steatosis in liver tissue, as well as AST, ALT and LDH after injection of LG in the ischemia (p <0.001). Lower levels of IL-6 and TNF-alpha were associated with LG infusion during ischemia. Higher levels these proteins were observed in animals receiving LG during reperfusion. CONCLUSION: L-arginine protects the liver against ischemia/reperfusion injury, mainly when is administered during the ischemic phase.

OBJETIVO: Investigar os efeitos da infusão endovenosa da L-arginina (LG) na morfologia, função e resposta de citocinas pró-inflamatórias do fígado durante a fase precoce da lesão de isquemia e reperfusão (IRI). MÉTODOS: Trinta coelhos foram submetidos a 60 minutos de isquemia hepática e 120 minutos de reperfusão. Foi administrada injecção intravenosa de solução salina ou L-arginina aos cinco minutos antes de iniciar a isquemia e cinco minutos antes de iniciar a reperfusão e aos 55 e 115 minutos após o início da isquemia. Realizou-se análise histológica do fígado e dosagens séricas de AST, ALT, LDH, citocinas IL-6 e TNF-alfa. RESULTADOS: Ocorreu redução significante da congestão sinusoidal, vacuolização citoplasmática, infiltração de leucócitos polimorfonucleares, picnose nuclear, necrose e esteatose no tecido hepático, assim como nos níveis de AST, ALT e LDH após a injeção da LG na isquemia (p<0,001). Níveis mais baixos de IL-6 e TNF-alfa foram associados com a infusão LG durante a isquemia. Níveis mais elevados dessas proteínas foram observados nos animais que receberam LG durante a reperfusão. CONCLUSÃO: A L-arginina protegeu o fígado contra a lesão de isquemia e reperfusão principalmente quando administrada durante a fase de isquemia.

L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury / A L-arginina durante a fase isquêmica protege o fígado das lesões de isquemia e reperfusão

PURPOSE: To investigate the effects of intravenous L-arginine (LG) infusion on liver morphology, function and proinflammatory response of cytokines during the early phase of ischemia-reperfusion injury (IRI). METHODS: Thirty rabbits were subjected to 60 minutes of hepatic ischemia and 120 minutes of reperfusion. An intravenous injection of saline or L-arginine was administered five minutes before the ischemia and five minutes before initiating the reperfusion and at the 55th and 115th minutes after the ischemia. Samples were collected for histological analysis of the liver and measurements of the serum AST, ALT and LDH and the cytokines IL-6 and TNF-alpha. RESULTS: It was observed a significant reduction of sinusoidal congestion, cytoplasmic vacuolization, infiltration of polymorphonuclear leukocyte, nuclear pyknosis, necrosis and steatosis in liver tissue, as well as AST, ALT and LDH after injection of LG in the ischemia (p <0.001). Lower levels of IL-6 and TNF-alpha were associated with LG infusion during ischemia. Higher levels these proteins were observed in animals receiving LG during reperfusion. CONCLUSION: L-arginine protects the liver against ischemia/reperfusion injury, mainly when is administered during the ischemic phase.(AU)

OBJETIVO: Investigar os efeitos da infusão endovenosa da L-arginina (LG) na morfologia, função e resposta de citocinas pró-inflamatórias do fígado durante a fase precoce da lesão de isquemia e reperfusão (IRI). MÉTODOS: Trinta coelhos foram submetidos a 60 minutos de isquemia hepática e 120 minutos de reperfusão. Foi administrada injecção intravenosa de solução salina ou L-arginina aos cinco minutos antes de iniciar a isquemia e cinco minutos antes de iniciar a reperfusão e aos 55 e 115 minutos após o início da isquemia. Realizou-se análise histológica do fígado e dosagens séricas de AST, ALT, LDH, citocinas IL-6 e TNF-alfa. RESULTADOS: Ocorreu redução significante da congestão sinusoidal, vacuolização citoplasmática, infiltração de leucócitos polimorfonucleares, picnose nuclear, necrose e esteatose no tecido hepático, assim como nos níveis de AST, ALT e LDH após a injeção da LG na isquemia (p<0,001). Níveis mais baixos de IL-6 e TNF-alfa foram associados com a infusão LG durante a isquemia. Níveis mais elevados dessas proteínas foram observados nos animais que receberam LG durante a reperfusão. CONCLUSÃO: A L-arginina protegeu o fígado contra a lesão de isquemia e reperfusão principalmente quando administrada durante a fase de isquemia.(AU)