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Biomedical subjects

F Filipponi

Publications and source records attributed to F Filipponi.

At least 55 records · Page 3Linked to original sources
PubMed1996

Surgical research in orthotopic liver transplantation: experiences in the pig model.

Since the very beginning of liver transplantation in humans, research in animals has had close relationship with clinical practice. Results obtained in animals have been transferred to the clinics and problems borne in the clinics have been addressed again in animals for to be answered clearly. In this review the authors report their experience of transplantation in the pig model and discuss the significance of a team cooperation in the laboratory as a preparatory step for clinical practice.

Anesthesia↗
PubMed1995

Segmental organization of the pig liver: anatomical basis of controlled partition for experimental grafting.

Segmental anatomy has been investigated on 54 pig livers by bench-top radiology and ultrasonography of hepatic and portal vessels and bile ducts and dissection of suprahepatic veins. Eight segments were recognized, homologous to those of the human liver. Major variations were found only of arterial distribution. The inferior vena cava invariably ran within the parenchyma of the right lobe and close to the liver hilum; suprahepatic veins were also entirely intraparenchymal. Therefore, the pig liver can easily be divided into two halves, but only the right one can be used for reduced-size grafting into a recipient.

Animals↗
PubMed1994

Liver transplantation for end-stage liver disease associated with alpha-1-antitrypsin deficiency in children: pretransplant natural history, timing and results of transplantation.

Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also not known why only a small proportion of Pi ZZ individuals progress towards cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficiency, patients are considered candidates for liver transplantation. In this paper, the natural history of 16 children who underwent liver transplantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in all children by the age of 12 months. In 11 children, jaundice recurred, always with liver function deterioration. Two patients had a histological paucity of interlobular bile ducts and required early transplantation due to rapid progression of liver failure. At the time of pretransplant assessment, all the patients in this study had portal hypertension and seven of them had experienced at least one episode of gastrointestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficiency. Eighteen orthotopic liver transplantations were performed in 16 patients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up of 22 months with an excellent quality of life, normal serum alpha-1-antitrypsin levels and without evidence of liver disease recurrence or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1994

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.

Adult↗
PubMed1992

Orthotopic liver transplantation in the pig: a surgical experience with 124 liver transplants.

From January 1988 to June 1990 one-hundred-twenty-four orthotopic liver transplantation (OLT) were performed in pigs, using a surgical procedure already described in the literature but with two major modifications. One of these modifications was the end-to-end microsurgical anastomosis of the proper hepatic arteries of the donor and recipient; the second one was the reduction in length of the donor suprahepatic vena cava to 1-2 mm before anastomosing it with the recipient suprahepatic vena cava at the level of the diaphragm. The first 24 transplants were used to develop the surgical technique. The latter was then applied to all subsequent 100 transplants, and results are herein presented. Good outcome of surgery appeared to depend on the modifications adopted in surgical technique, use of a pump-driven veno-venous bypass during the anhepatic phase of surgery, administration of cyclosporin A postoperatively, and training of the operator.

Anastomosis, Surgical↗
PubMed1991

A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury.

In this research, the effects of portocaval shunt plus 70% partial hepatectomy were evaluated in 11 pigs. Hepatic coma and death from progressive liver failure occurred in 5 pigs between 14 and 64 h from surgery, whereas 3 pigs, which also showed symptoms of progressive liver failure, died of presumed gastric hemorrhage between 17 and 19 h after surgery. In 3 pigs, transient liver failure was followed by complete recovery, as judged by clinical, electroencephalographic and biochemical parameters. No case of death occurred among the pigs treated with portocaval shunt alone or 70% partial hepatectomy alone as controls. This new model for acute liver failure is reproducible, seems to be potentially reversible, causes death due to hepatic failure after a time period sufficiently long to allow for the institution of support procedures, is applied to a large animal and lacks relevant biohazard. Therefore, this model may be used to evaluate possible support procedures during acute liver failure.

Ammonia↗
PubMed1990

Immunocytochemical and ultrastructural changes of islet cells in rats treated long-term with cyclosporine at immunotherapeutic doses.

Daily cyclosporine doses of 10 mg/kg body weight for 21 days in Wistar rats cause impairment in glucose homeostasis and changes in the amount of immunostainable hormones and in the ultrastructure of the cells of the pancreatic islets. CsA induces hyperglycemia and reduced glucose tolerance, and causes a decrease in immunoreactive insulin and an increase of somatostatin and pancreatic polypeptide (PP) immunoreactivities, leaving glucagon immunoreactivity unaffected. Ultrastructurally, different degrees of dilation of rough endoplasmic reticulum cisternae and enlargement of Golgi apparatus can be observed in B cells, together with a pronounced reduction in the number of secretory granules. Nevertheless, there were no apparent morphological changes of the other cytoplasmic organelles, suggesting that the drug, besides a depression of protein synthesis, as previously stated, also induces a substantial defect in granulogenesis, probably due to impairment in the intracellular transport of the hormone from the sites of synthesis to the secretory granules. The B cell alterations are not accompanied by any sign of B cell degeneration or death. Non-B cells did not show any of the ultrastructural changes found in B cells and were similar to those of the control rats. The above findings indicate that CsA at immunotherapeutic doses causes impairment in the secretory processes of B cells specifically. An hypothesis on the mode of action of CsA on B cells is drawn.

Animals↗
PubMed1990

Morphological changes in rat pancreatic acinar cells induced by long-term treatment with cyclosporine and their reversal after withdrawal.

Cyclosporine (CsA), administered to rats at daily doses of 10 and 50 mg/kg body weight, for 21 days, influenced negatively the structures involved in the synthesis, storage and secretion of digestive enzymes in pancreatic acinar cells. A dose-related, significant reduction in basophilic cell regions, secretion granule content, and overall size of acinar cells was appreciable by light microscopy and morphometry. By electron microscopy, the acinar cells of the rats given 10 mg/kg/day CsA were similar to the controls, whereas with the higher dose most cells showed reduction in the size of nucleoli, increase in the number of lysosomes, and evidence of autophagy. In only a few cells was autophagy particularly severe and involved almost the entire cytoplasm. Nine weeks after withdrawal from CsA treatment, the structural recovery of acinal cells was complete, and features indicating enhanced protein synthesis and mitochondrial multiplication were observed by electron microscopy. In conclusion, prolonged administration of CsA to rats induces changes in the acinar cells indicating a depression of their activity, without substantial impairment in the viability of the most of them, even at high doses. This accounts for complete restoration of the acinar tissue upon withdrawal.

Animals↗
PubMed1990

Bioavailability of intramuscular ciclosporin in the pig.

We conducted a cross-over single-dose pharmacokinetic study in 4 pigs to measure the bioavailability of ciclosporin (CS) after intravenous and intramuscular administration. Each animal was given 5 mg/kg i.v. followed by 20 mg/kg i.m. after 1 week. Serial blood samples were taken over 36 h after each dose, and the concentration of CS was assayed by radioimmunologic methods. The pharmacokinetic parameters after intravenous administration were (mean +/- SD; n = 4): clearance = 327 +/- 21 ml/h/kg; volume of distribution = 7.2 +/- 2.8 liters/kg. The same parameters after intramuscular dosing were: clearance = 326 +/- 59 ml/h/kg; volume of distribution = 6.9 +/- 2.1 liters/kg. The percent bioavailability of intramuscular CS was 101.9 +/- 13.3 with a mean absorption time of 10.6 +/- 2.7 h. Our results indicate that following a single dose, the percent bioavailability of intramuscular CS in pigs is considerably greater than that reported in previous studies.

Animals↗
PubMed1990

Alterations in the fine structure of the pig liver upon cold ischemia.

The fine structure of the pig liver was examined after 30 min of warm ischemia at 37 degrees C, after 2 h of cold ischemia at 4 degrees C and after 30 min of warm ischemia followed by a further 30 min of cold ischemia. After warm ischemia, limited mitochondrial swelling was observed in hepatocytes. After cold ischemia, alone or following warm ischemia, vesiculation and vacuolation of the hepatocyte cytoplasm and appearance of intrasinusoidal blebs deriving from hepatocytes were observed with different intensity among the animals. These findings suggest that cooling and storing the liver at 4 degrees C may lead to injury, which could negatively influence the viability of the organ, with different intensity from case to case.

Animals↗
PubMed1990

Veno-venous bypass in experimental liver transplantation: portal-jugular versus caval-portal-jugular.

This study was undertaken to compare the changes in physiologic variables caused by the use of two different types of pump-assisted veno-venous bypass during experimental liver transplantation. The experiments, performed on female pigs weighing 30 +/- 2 kg, were divided into two groups depending on the bypass used. During the anhepatic phase a pump-assisted portal-jugular (PJ) bypass was used in Group 1 (n = 8) at a flow rate of 15 ml kg-1-min-1, while a pump-assisted caval-portal-jugular (CPJ) bypass was used in Group 2 (n = 8) at a flow rate of 20 ml kg-1-min-1. Intraoperative haemodynamics, pulmonary gas exchange, haematological and serum biochemical parameters were evaluated. Postoperative animal survival rate and complications associated with the bypass used were evaluated. Mean pulmonary artery pressure (Ppa) and pulmonary vascular resistance (Pvr) showed significantly different behaviour in the two groups, whereas the remaining parameters all showed the same trend. Thus an earlier and more substantial increase in Ppa and Pvr values was found in Group 1 when compared to Group 2 during the anhepatic phase. The different behaviour shown by Group 1 may depend on the release of circulating vasoactive substances generated following pelvic venous congestion caused by the temporary clamping of the inferior vena cava. In conclusion, this study indicates that the pump-assisted CPJ bypass is more suitable than the pump-assisted PJ bypass. Furthermore, in order to obtain better results it should be used routinely in porcine liver transplantation.

Anesthesia, General↗
PubMed1989

Prolongation of guinea pig-to-rat xenograft survival with BN 52063, a specific antagonist of platelet-activating factor.

Xenotransplantation between different species may possibly solve some of the difficulties associated with human donor organ availability. However, organ xenografts are very rapidly rejected, particularly in discordant donor-recipient combinations, due to the presence of natural cytotoxic antibodies in the recipient. The purpose of this study was to evaluate the efficacy of two potential inhibitors of a xenogeneic antigen-antibody reaction: Iloprost, an analogue of prostacyclin I2, and BN 52063, a PAF-antagonist. Heart (group A) or liver (group B) transplantations were performed in the guinea pig-to-Lewis rat donor-recipient combination. Fifteen minutes prior to revascularization of the graft an intravenous infusion was instituted using saline (0.01 ml/min) (groups A1 and B1), saline and dimethylsulfoxide (DMSO, 0.1 ml/min) (groups A2 and B2), Iloprost (2 ng/Kg/min) (groups A3 and B3) or BN 52063 (6 mg/Kg/min) (groups A4 and B4). Heart graft survival times (min) were 12.3 +/- 1.7 (A1), 13.4 +/- 2.2 (A2), 14.8 +/- 1.0 (A3), 18.3 +/- 1.4 (A4). Liver graft survival times (min) were 158.4 +/- 38.9 (B1), 129.6 +/- 14.4 (B2), 168.1 +/- 18.0 (B3) and 306.2 +/- 36.5 (B4). A significant prolongation (p less than 0.05) was observed in group A4 versus A1, A2, A3 and in group B4 versus B1, B2, B3. These results suggest that prevention of xenograft rejection using PAF-antagonist in association with other methods should be further investigated.

Animals↗
PubMed1989

[Development of an orthotopic hepatic transplantation technique in rats: what should the researcher's objectives be?].

The development of liver transplantation in man emphasises the need for more work in the field of experimental liver transplantation. For this purpose the model of orthotopic liver transplantation in the rat is very useful but difficult to establish as a safe and reproducible technique. The aim of this study concerning acquisition of the orthotopic liver transplantation model in the rat was to define precise objectives for future investigators. Two investigators without experience in microsurgery each performed 75 orthotopic liver transplantations, which were divided into five consecutive series. In each series survival times of the recipients after transplantation were analysed according to the mean duration of the operative procedure and the mean portal vein clamping time. For each investigator, mean duration of the operative procedure progressively decreased to reach a minimum at the 45th graft. From that time on, the portal vein clamping time became less than 17 minutes and a significant increase in the post operative survival time of the recipient was observed. However it was only from the sixtieth transplantation on, with stable portal vein clamping time but technical mistakes fewer that a high success rate was observed.

Anastomosis, Surgical↗