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Biomedical subjects

F Filipponi

Publications and source records attributed to F Filipponi.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1989

Biliary tract complications in orthotopic liver transplantation: an experimental study in the pig.

The results of 56 consecutive orthotopic liver transplants in the pig were reviewed to determine the incidence of primary biliary tract complications. There were 8 biliary tract complications in 56 grafts (14.2%) directly responsible for death. End-to-end choledochocholedochostomy (ee-CC) was the most frequently used technique (40 cases) with 4 technical failures (10.0%). Choledochojejunostomy with a Roux-en-Y jejunal loop (RYCJ) was used in 9 cases with 2 technical failures (22.2%). Side-to-side choledochocholedochostomy (ss-CC) was used in 7 cases with 2 technical failures (28.5%). Biliary leak and stenosis were the most common complications. End-to-end choledochocholedocostomy appears to be the most suitable and easy biliary reconstruction in the pig but possible gross disparity in the sizes of the donor and recipient ducts may represent and adverse factor.

Anastomosis, Roux-en-Y↗
PubMed1988

One liver for two: an experimental study in primates.

The need for liver grafts is critical in countries where brain death is not accepted as a legal criterion for organ retrieval. This experimental study was conducted with nonhuman primates in order to evaluate the feasibility of liver transplantation using a living donor. An original technique was employed to remove the left part of the liver from the donor: transection of the parenchyma was done while the blood flow was kept to the left part of the liver. In the recipients, the graft was placed heterotopically. No blood transfusions were administered to donors or recipients. In spite of a few failures, due to consequences of intraoperative bleeding, several donor operations using this original technique were successful, in the immediate postoperative period as well as several months later. Among the recipients, the large number of early failures suggests that the heterotopic position is probably not the appropriate one and that orthotopic transplantation should be preferred.

Animals↗
PubMed1988

Prevention of death following one-hour occlusion of the portal vein in the rat.

This study was conducted to evaluate various methods to reduce the mortality rate following acute portal vein occlusion in rat: systemic heparinization, intravenous saline infusion, enteral antibiotics and simultaneous clamping of the superior mesenteric artery were tested alone or in combination. Each of these treatments improved the survival rate after 45 or 60 min occlusion of the portal vein; combination of all treatments provided better results than each treatment alone. These results indicate that, following acute portal vein occlusion in the rat, several factors cooperate to cause death. The decrease in mean arterial blood pressure during occlusion of the portal vein was correlated with the mortality rate; this correlation was significant in the animals with 45 min occlusion of the portal vein. It appeared in this study that, when used in association, simple therapeutic methods are highly effective in improving the survival rate following acute portal vein occlusion in the rat.

Animals↗
PubMed1988

Liver transplantation in the rat: surgical experience with 212 liver transplants.

A technique is described for orthotopic liver transplantation in the rat using polyethylene cuffs to re-establish subhepatic cava and portal vascular anastomoses. This procedure reduces the time of portal clamping, an important factor of survival. This technique was found to be reliable with a 72.9% long-term survival (more than 60 days) in an experimental group of 59 iso- and allografts. The method was employed in 212 animals during studies on iso-, allo- and xenografts to evaluate the tolerance and rejection mechanisms in rats of pure strain.

Animals↗
PubMed1988

Discordant heart xenografts in the rat. Additional effect of plasma exchange and cyclosporine, cyclophosphamide, or splenectomy in delaying hyperacute rejection.

Natural antidonor antibodies are known to play a prominent role in hyperacute xenograft rejection. The aim of this work was to devise an experimental protocol to prolong the survival time of guinea pig heart xenografts transplanted into rats. A technique of continuous plasma exchange adapted to small animals was used to remove the natural cytotoxic antibodies from the recipient prior to the transplantation. In some experiments, cyclosporine (CsA), cyclophosphamide (CY), or splenectomy were associated with the plasma exchange. In this highly discordant xenogenic donor-recipient combination, the mean graft survival time in nontreated rats was 16 min. When an exchange of 1.5 plasma volume was performed 24 hr before the transplantation, no prolongation of the graft survival time was observed. When CsA, CY, or splenectomy were associated with the plasma exchange, the graft survival time was significantly increased by more than 2500% (up to 418 min with CsA). When used isolately, none of these 3 immunosuppressive methods was able to prolong the graft survival time. Natural cytotoxic antibodies were monitored by a complement-mediated cytotoxicity assay. After a plasma exchange, the titers decreased from 1:16-1:32 to 1:1-1:2. When no immunosuppressive method was associated with the plasma exchange, the antibodies returned to their initial level within the 24 hr that preceded the transplantation, and the graft was rejected as in nontreated animals. When an immunosuppressive method was associated with the plasma exchange, and particularly in the case of CsA, the titers remained low, and the hyperacute rejection was delayed. Therefore, it can be concluded that plasma exchanges, associated with CsA, are an efficient experimental protocol in the rat to increase the survival time of guinea pig heart xenografts. The effect of the treatment is correlated with the decrease in natural cytotoxic antidonor antibodies.

Animals↗