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Biomedical subjects

I Marzi

Publications and source records attributed to I Marzi.

86 records · Page 5Linked to original sources
PubMed1991

Hepatic microcirculatory disturbances due to portal vein clamping in the orthotopic rat liver transplantation model.

Most modifications and applications of the orthotopic rat liver transplantation (ORLT) model require clamping of the portal vein, thus leading to ischemia of the gut. The purpose of this study was to evaluate the effect of portal vein clamping during ORLT on hepatic microcirculation and leukocyte--endothelial interaction by intravital fluorescence microscopy. ORLT were performed following 1 hr of cold storage in EuroCollins solution without (standard group) and with insertion of a portojugular shunt (shunt group) to minimize intestinal ischemia. ORLT induced reduction of perfused sinusoids (83%) and velocity of leukocytes (311 +/- 4.5 microns/sec; mean +/- SEM) compared with nontransplanted controls (99% and 417 +/- 4.9 microns/sec). Portojugular shunt during ORLT improved hepatic microvascular perfusion (89% and 355 +/- 3.4 microns/sec; P less than 0.05). Furthermore, percentage of permanent and temporary adherent leukocytes decreased significantly when a portosystemic shunt was applied (from 33.5 +/- 1% to 22.1 +/- 1% and 19.7 +/- 1.2% to 14.0 +/- 0.9%; P less than 0.05). The results of the study reveal that intestinal congestion and reperfusion results in a rise in leukocyte adhesion to the sinusoidal wall and in disturbances of the hepatic microcirculation. It seems likely that increased endotoxin concentrations in the portal vein induce an activation of hepatic macrophages that subsequently cause release of chemoattractant mediators. In conclusion, side effects of intestinal ischemia during experimental liver transplantation surgery on liver function due to release of chemoattractant mediators should be considered when experimental data are transferred to clinical settings.

Animals↗
PubMed1991

In vivo fluorescence microscopy for quantitative analysis of the hepatic microcirculation in hamsters and rats.

Using intravital fluorescence microscopy and epi-illumination, the hepatic microcirculatory system of Syrian golden hamsters was analyzed, and the morphology and microhemodynamics were compared to those of rats. After contrast enhancement with 1 mumol/kg acridine orange i.v., the epi-illumination technique allows for visualization of capillary sinusoids and postsinusoidal venules, which are running in parallel with the liver surface, while afferent microvessels could be visualized in only few of the liver lobules investigated. In rat livers, the capillary sinusoids showed morphology similar to that of hamsters, however, postsinusoidal venules could frequently not be observed when applying epi-illumination, since these microvessels are piercing perpendicularly into the depth of the liver tissue. Microhemodynamic analysis, including the sinusoidal perfusion rate, sinusoidal red blood cell velocity and diameters, microvascular white blood cell (WBC) count and the phenomenon of WBC-endothelium interaction, as well as the hepatocellular uptake of the fluorescent compound acridine orange were found to be similar in hamsters as compared to rats. Although transillumination for in vivo microscopy may have the potential to visualize the complete hepatic microcirculatory system due to an increased focus depth, the epi-illumination technique has the advantage for quantitative assessment not only of the morphology of the hepatic microcirculatory system and microvascular blood perfusion, but also allows for evaluation of cellular phenomena within the hepatic microvessels, such as WBC accumulation, WBC-endothelium interaction, phagocytotic activity of Kupffer cells, and hepatocellular transport of fluorescent compounds. Hepatic microcircular disturbances, including accumulation of WBCs and WBC-endothelium interaction are causative in the development of organ failure in conditions such as hemorrhagic and septic shock, and, in particular, postischemic reperfusion injury following liver surgery and liver transplantation. Since accumulation of WBCs and their interaction with the microvascular endothelium are primarily found in postsinusoidal venules, in vivo microscopy of the hamster liver represents a favorable model for studies on cellular phenomena within the hepatic microcirculation.

Animals↗
PubMed1990

Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine.

Kupffer cells are activated by calcium and release a variety of toxic mediators, including proteases. The purpose of these studies, therefore, was to determine if protease inhibitors and a calcium channel blocker could increase survival time in the rat model of orthotopic liver transplantation. Survival for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution (survival conditions)--however, grafts stored for 4 hr in Euro-Collins solution or 8 hr in University of Wisconsin (UW) solution survived postoperatively only 1.2 and 0.7 days, respectively (nonsurvival conditions). When livers were stored for 4 hr in Euro-Collins containing a cocktail of protease inhibitors (leupeptin, pepstatin A, phenylmethylsulfonyl fluoride, 20 ng/ml each; diisopropyl fluorophosphate, 100 microM) and subsequently transplanted, however, survival time was increased significantly to 11.5 days. Inclusion of a calcium channel blocker, nisoldipine (1.4 microM), in the protease inhibitor cocktail increased survival time to 23 days. Actually, nisoldipine alone increased survival time to 25 days. Nisoldipine alone also increased survival time in livers stored for 8 or 16 hr in UW solution to between 15 and 20 days. Serum transaminase levels reached peak values greater than 2400 U/L one day postoperatively in the nonsurvival groups, and liver injury assessed histologically was apparent. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 60% of the lungs examined and was associated with massive bleeding. Inclusion of the protease cocktail, nisoldipine, or both in the storage solutions decreased maximal SGOT levels and injury to both liver and lung significantly by about 50% postoperatively. Nisoldipine also decreased phagocytosis of carbon particles by the perfused liver 2- to 3-fold following storage under nonsurvival conditions (half-maximal effect = 0.3-0.4 microM nisoldipine). Moreover, nisoldipine improved hepatic microcirculation. It accelerated blood flow into the liver, as indexed by hemoglobin reflectance from the liver surface. These data support the hypothesis that Kupffer cells are activated early in the sequence of events that causes graft failure leading to endothelial cell-mediated alterations in the microcirculation. This work demonstrates clearly that dihydropyridine-type calcium channel blockers such as nisoldipine may be clinically useful in storage solutions for liver prior to transplantation.

Animals↗
PubMed1990

[Indications and technic of external fixation in acute management of polytrauma].

The application of external fixation in the multiple injured patient permits rapid stabilisation of fractures and excellent preservation of soft tissue without an additional systemic load after traumatic shock. Acute fixation in the primary care is achieved by particular constructions for the pelvis and femur and modifications of standard-techniques for the tibia and joint-transfixation. In most cases secondary completions or alterations in the method of treatment are necessary.

Femoral Fractures↗
PubMed1989

Pancreatic autotransplantation in the pig: variations in epigastric arterial blood supply.

A major problem in pancreatic autotransplantation is the vascular supply of the left segment, which serves as the graft. We therefore examined the arterial blood supply of the epigastric organs in 36 German landrace pigs. In 19 pigs (anatomical variation 1) there was a pancreatic branch of the splenic artery supplying the left segment. After splenectomy the splenic artery could be used as the graft-supplying vessel. In 14 pigs (anatomical variation 2) the arterial branch for the left segment was the first branch out of the hepatic artery distal to the coeliac trunk. In these cases a splenohepatic bypass was performed to ensure delivery of the blood to the epigastric organs. Thereafter, the proximal part of the hepatic artery could be used as the vessel supplying the graft. The left segment could not be used for autotransplantation in 3 pigs (anatomical variation 3) because of the atypical vascular supply. During the 6-month observation period, no malfunction of the epigastric organs was evident.

Animals↗
PubMed1989

Evidence that graft survival is not related to parenchymal cell viability in rat liver transplantation. The importance of nonparenchymal cells.

Injury to parenchymal and nonparenchymal cells of livers stored in cold Euro-Collins solution was assessed following reperfusion and compared with graft survival following orthotopic rat liver transplantation. Parenchymal cells maintained their viability nearly completely after up to 24 hr of cold storage as assessed by trypan blue exclusion (97% of cells) and LDH release (4% of total) from livers reperfused for 20 min following storage. Furthermore, hepatic glycolysis (rates of lactate plus pyruvate production), oxygen uptake and NADH redox state (lactate:pyruvate ratio) were in the normal range at all time points studied up to 24 hr of cold storage. In contrast, nonparenchymal cells lost viability as assessed from trypan blue staining beginning after 8 hr of storage: 40% were nonviable after 24 hr of storage. Since injury to nonparenchymal cells occurs only upon reperfusion, oxygen radicals may be involved. Accordingly, xanthine and hypoxanthine, substrates for oxygen radical formation, were measured in perfusate upon reperfusion. Both purines accumulated (up to 80 microM) with time of storage and were washed out rapidly (less than 10 min) upon reperfusion. Although parenchymal cell function was in the normal range in livers stored in the cold for 24 hr, liver grafts stored for 6 hr and longer in Euro-Collins solution could not be transplanted successfully. Thus, we conclude that viability of parenchymal cells in liver grafts prior to transplantation is a poor parameter to predict the outcome of transplantation. Therefore, assessment of parenchymal cell energy state (e.g., with 31P NMR and other methods) most likely will not predict survival reliably. On the other hand, nonparenchymal cells lose their viability significantly earlier following storage and reperfusion. These data suggest that preservation of nonparenchymal cell viability is critical for successful liver transplantation.

Animals↗
PubMed1988

Hepatic reperfusion injury following orthotopic liver transplantation in the rat.

At 24 hr following orthotopic transplantation, rat liver grafts were perfused in situ for 7 min with trypan blue, a vital dye that provides information on hepatic microcirculation and stains nuclei of nonviable cells. Spotty and uneven dye distribution was observed indicating that hepatic microcirculation was disturbed 24 hr following transplantation surgery. Under these conditions, 15-20% of the hepatocytes were nonviable as assessed from trypan blue staining and frank necrosis. In contrast, perfusion of livers from untransplanted rats or liver explants exposed to cold ischemia for 60 min were judged normal by the criteria of uniform distribution of dye in the organ and absence of necrosis and nuclear dye uptake. Thus the observed damage was associated with reintroduction of blood and can therefore be classified as a reperfusion injury. The altered microcirculation and cell death following the operation was reduced markedly by perfusion of the cold, ischemic explant with nitrogen-saturated but not with oxygen-saturated buffer for 5 min prior to the implantation operation. Protection was even greater if the perfusion medium contained verapamil (20 micrograms/ml), a Ca++ channel blocker. We conclude that reperfusion of the stored liver causes an oxygen-dependent alteration in hepatic microcirculation that leads to hypoxia and scattered hepatocellular necrosis in the implanted graft. Brief perfusion of the hypoxic implant under anaerobic conditions may remove substrates involved in oxygen radical generation and prevent reperfusion injury upon introduction of oxygen into the graft via the blood. Taken together, these results suggest that removal of Euro-Collins' solution under anaerobic conditions may be beneficial clinically in preventing injury of surgical explants.

Animals↗