Abstract: We reviewed the literature reports and our personal experience on partial portal vein arterialization (PPVA) to prevent and treat acute liver failure (ALF) following major hepatobiliary surgery or another etiology. Experimental studies in rats have assessed the efficacy of PPVA in treatment of ALF induced by extended resections in normal or fatty livers or in toxic carbon-tetrachloride damage. The treated groups showed greater survival and faster recovery of liver function. Among 11 clinical cases reported in the literature, PPVA was performed in four cases to prevent and in seven cases to treat ALF. Eight patients survived, showing rapid recovery of liver function and resolution of the clinical condition. This relatively simple procedure has shown itself able to promote liver regeneration. The PPVA procedure has shown itself to be safe and simple as well as to offer a promising approach to the failing liver.

Abstract: INTRODUCTION: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors. The aim of our study was to test the effect of meraxin, a new derivative from repertaxin, to protect the renal graft from ischemia and reperfusion injury. MATERIALS AND METHODS: Eighty male syngenic rats were divided into four groups. The control group underwent only kidney transplantation, while the other groups were treated with meraxin at various dosages 2 hours before graft reperfusion. Blood and histological samples were taken at sacrifice 24 hours after transplantation. RESULTS: Creatinine was significantly lower in the group treated with the high dosage of meraxin. Histological observation of the grafted tissue showed instead only a mild and not significant neutrophilic infiltration, equal in each group. CONCLUSIONS: Graft function was improved by the administration of meraxin at high dosage, but this effect did not seem to be connected to a reduction in inflammatory infiltration in the parechymal tissue. Maybe the cause is in the mechanisms of clotting activation, due to alteration of adhesion molecules and endothelial cells.

Abstract: INTRODUCTION: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of this study was to verify the results obtained with double-kidney transplantation in terms of graft/patient survivals and complications. PATIENTS AND METHODS: Between September 2001 and September 2006. 26 double-kidney transplantations were performed in our center. Indications for surgery were: chronic glomerulonephritis (n = 17), polycystic disease (n = 4), reflux nephropathy (n = 1), hypertensive nephroangiosclerosis (n = 4). The kidneys were all perfused with Celsior solution and mean cold ischemia time was 16.7 +/- 2.5 hours. In all cases, a pretransplant kidney biopsy was performed to evaluate the damage (mean score: 4.3). Immunosuppression was tacrolimus-based for all patients. RESULTS: Eighteen patients had good renal postoperative function, while the other eight displayed acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31%. There were two surgical reoperations for intestinal perforation. Graft and recipient survivals were 82.7% and 100%, and 78.9% and 94% at 3 and 36 months, respectively. CONCLUSIONS: Double-kidney transplantation is a safe strategy to face the organ shortage. The score used in this study is useful to determine whether a kidney should be refused or suitable for single- or dual-kidney transplantation. The results of our experience are encouraging, but the series is too small to allow a conclusion.

Abstract: INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.

Abstract: INTRODUCTION: Optimization of the conditions for regeneration of the native diseased liver is a major goal in patients with acute liver failure. This study sought to determine whether portal vein arterialization (PVA), which increases the oxygen supply to the liver, was protective in a rat model of liver failure. METHODS: At 24 hours after CCl(4) intoxication, Sprague-Dawley rats (six per group) were assigned to receive PVA or as controls. We determined blood tests, histology, and 10-day survivals. Hepatocyte regeneration was assessed by the mitotic index and bromodeoxyuridine (BrdU) incorporation. RESULTS: Serum transaminases were significantly lower in PVA-treated rats than in control animals: liver necrosis resolved rapidly after PVA. The BrdU staining and mitotic index were severalfold higher among PVA-treated than in untreated rats. Survival was 100% among rats with PVA and 40% in untreated animals (P < .01). CONCLUSIONS: PVA led to resolution of CCl(4)-induced massive liver necrosis in the rat. This effect was probably mediated by activation of rapid and extensive hepatocyte regeneration. PVA might provide a novel, alternative approach to treat acute liver failure.

Abstract: AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.

Abstract: Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.

Abstract: AIM: To determine whether the increase of oxygen supply in the portal system by a liver extracorporeal (L.E.O.NARDO) device is effective in treating swine with subtotal hepatectomy leading to acute liver failure (ALF). METHODS: Eight swine with ALF induced by 85% to 90% liver resection and 5 minutes of ischemia-reperfusion injury were randomly divided into two groups: four animals received L.E.O.NARDO treatment and four swine were not treated (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system. An extracorporeal device was interposed between the outflow and the inflow in order to monitor the hemodynamic parameters. Each treatment lasted 6 hours. Serum and liver samples were collected in both groups. The survival was assessed at 1 week. RESULTS: L.E.O.NARDO treatment yielded beneficial effects for subtotal hepatectomy-induced ALF in swine with decreased serum transaminases as compared with the untreated group. International normalized ratio recovered rapidly in the L.E.O.NARDO group, remaining significantly lower than in untreated animals. The 7-day survival of L.E.O.NARDO group swine was significantly higher than that of untreated animals, with a significant difference. Three swine in the L.E.O.NARDO group survived 1 week while none of the swine in the control group were alive at that time. CONCLUSIONS: Oxygen supply in the portal vein through the L.E.O.NARDO device is easily applicable, efficacious, and safe and may represent a novel approach for ALF in swine induced by subtotal liver resection.