摘要:

Conflicting data have been reported on the relationship between reactive oxygen intermediates and the formation of oxygenase-derived eicosanoids. Plasma levels of prostacyclin (PGI2, measured as the stable metabolite 6-keto-PGF1α) and thromboxane A2 (TxA2, measured as TxA2) in the effluent blood of a canine ileal segment were determined following 1 or 2 h of ischemia. The synthesis of both eicosanoids was significantly stimulated during reperfusion, but extension of the ischemic interval from 60 to 120 min was not followed by a further increase. The role of oxidants potentially involved in the process was investigated by using materials that inactivate the xanthine-oxidase-generated intermediates. Previous studies on the same in vivo animal model had demonstrated the effectiveness of antioxidant therapy in reducing the postischemic histamine release. There was no significant alteration in the amount of eicosanoids synthesized following oral allopurinol, catalase, dimethylsulfoxide, mannitol or desferrioxamine treatment. Intravenously administered allopurinol, however, significantly elevated the postischemic 6-keto-PGF1α/TxB2 ratio. The results suggest that these antioxidants at doses inhibitory to histamine liberation are not effective in influencing the postischemic eicosanoid release. Intravenously administered allopurinol could exert a potentially beneficial effect through a mechanism other than the blockade of xanthine oxidas

ISSN:0014-312X    

DOI:10.1159/000129146

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

We perfused isolated rat livers with Krebs-Ringer buffer, with no recirculation. Bile flow virtually stopped during 30 min of anoxia and resumed following reoxygenation to reach a plateau of 44% of the control level. When taurodehydrocholic acid (TDHC, 50 nmol/ min/g liver) was administered during reoxygenation, bile flow increased three-fold (16.1 ± 1.3 to 45.3 ± 6.3 µl/g liver). The increase in bile output with TDHC was 27.8 µl/g liver, which was 89% of the control output. Bile acid output during this period was 1.4 µmol/g liver, which was 93% of the control level. Addition of allopurinol (50 nmol/min/g liver) without TDHC increased bile flow significantly (16.1 ± 1.3 to 21.3 ± 1.2 µl/g liver), but the change was not significant when allopurinol and TDHC were given. The addition of allopurinol also reduced the cumulative release of lactate dehydrogenase from the liver during the reoxygenation period, but had no effect on hepatic adenosine triphosphate levels. Our data suggest that the bile acid-independent bile flow is sensitive to reoxygenation injury following anoxia whereas bile acid output and bile acid-dependent bile flow are re

ISSN:0014-312X    

DOI:10.1159/000129147

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

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 µmol/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

ISSN:0014-312X    

DOI:10.1159/000129148

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In order to confirm a complete ischemia model, 1-hour warm hepatic ischemia by hepatic vascular exclusion (HVE) was studied in dogs, in comparison with that by inflow occlusion (IOC) only. The splanchnic venous bed and/or infrahepatic inferior vena cava were decompressed by a centripetal pump-driven venovenous bypass. Indocyanine green retention test revealed no hepatic blood flow in the HVE model during ischemia, while hepatic blood perfusion was still present in the IOC model. All 5 of the IOC dogs survived more than 7 days after revascularization, while 4 of the 5 HVE dogs died within 9 h. After the induction of hepatic ischemia, lactate increased in both HVE and IOC dogs. After revascularization, transaminases and guanase were elevated, the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate) decreased and the serum lactate accumulated more in HVE dogs than in IOC dogs. The hepatic redox state of IOC dogs was significantly decreased by additional clamping of the inferior vena cava. It is concluded that the HVE model with a pump-driven active bypass provides complete and stable hepatic ischemia, resulting in greater deterioration of hepatic cellular functions; hence it is more suitable as a model of complete hepatic ischemia than the IOC one.

ISSN:0014-312X    

DOI:10.1159/000129149

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

To study the blood flow in normal liver tissue and in liver malignancies after occlusion of the hepatic artery or the portal vein, an adenocarcinoma was inoculated in the left liver lobe of 10 rats. Eight days postoperatively, blood flow in normal hepatic tissue and tumour was estimated by laser Doppler flowmetry (LDF). In both normal tissue and tumour, occlusion of the hepatic artery reduced LDF values by approximately 30%, whereas occlusion of the portal vein reduced LDF values by approximately 70%. These findings indicate that changes of hepatic blood flow can be monitored by LDF, and that the portal blood flow is dominating also in liver metastasis.

ISSN:0014-312X    

DOI:10.1159/000129150

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

We performed 22 canine orthotopic partial liver transplantations (PLTs) with three different revascularization methods; portal vein arterialization (PVA group, n = 11), hepatic arterial shunt (HAS group, n = 5), and conventional portal vein reperfusion (control group, n = 6). Our purpose was to evaluate the feasibility of PVA as a revascularization technique in PLT assessing the changes in arterial ketone body ratio (KBR) as an index of hepatic energy status. After the first anastomosis (left hepatic vein), the ischemic partial liver graft was revascularized with arterial blood flow shunted from the external iliac artery to the hepatic side of the portal vein (PVA group) or the proper hepatic artery (HAS group). Both anhepatic period and ischemia time were significantly shortened in groups PVA and HAS as compared with those in control. In the PVA group, 10 out of 11 recipients survived for at least 5 days (14.2 ± 3.8 days, mean ± SEM), while 3 out of 5 (5.2 ± 1.0) survived in the HAS group and 4 out of 6 (6.2 ± 1.3) in the controls. Although portal blood flow during PVA was only about 25% of the total hepatic blood flow at preclamping, the KBR was rapidly restored after PVA and showed almost the same values at preclamping. The KBR values during the arterialization time and initial velocity of KBR recovery in the PVA group were significantly higher than those in the HAS and control groups. These results suggest that PVA presents an attractive option in

ISSN:0014-312X    

DOI:10.1159/000129151

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The purpose of this study was to determine the renal function derangements that portacaval shunting caused in previously normal rats. Eight rats suffered a surgical portacaval shunt (PCS) and another 8 a sham operation (SHAM). Renal function was investigated by determining urinary volume, sodium, potassium, creatinine and aldosterone excretion, in basal conditions and after sodium overload. Plasma renin concentration and urinary excretion of PGE2, 6-keto-PGF1α and TXB2 were also determined in basal conditions. PCS rats showed increased urinary volume, creatinine excretion and endogenous creatinine clearance, either in basal conditions or after sodium load. After the latter, PCS animals also showed sodium retention and hyperaldosteronuria. PCS caused in basal conditions a striking diminution in urinary excretion of all prostaglandins and no changes in plasma renin. In conclusion, PCS in the normal rat caused a renal dysfunction consisting of polyuria, possibly related to ADH disfunction and an inability to manage a sodium load

ISSN:0014-312X    

DOI:10.1159/000129152

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The effect of FK-506 on allograft survival in unsensitized recipients has been established in several animal experimental models. In this present study, we investigated the immunosuppressive capacity of FK-506, in comparison with ciclosporin (Cs) and 15-deoxyspergualin (DSG), on heart allografts in presensitized rats. Heart grafts from male ACI rats were heterotopically transplanted to male LEW rats. All recipient rats were sensitized with donor-type whole blood admixed with immunoadjuvant (adjuvant complete Freund) 7 days prior to transplantation. FK-506, Cs and DSG were administered from day 0 to day 14 posttransplantation. The results showed that both FK-506 and Cs significantly prolonged heart allograft survival of presensitized recipients in a dose-dependent manner. The minimum effective dose in the treatment was less for FK-506 than for Cs. However, DSG showed almost no effect of prolongation in this experiment.

ISSN:0014-312X    

DOI:10.1159/000129153

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was detemined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative period; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.

ISSN:0014-312X    

DOI:10.1159/000129154

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The purpose of this prospective randomized study was to determine whether prophylactic administration of urinary trypsin inhibitor prevents postoperative damage to the pancreas caused by R2 gastrectomy in patients with gastric cancer, by analyzing related enzyme activities. Among the 22 patients who underwent distal partial gastrectomy together with R2 lymphadenectomy, 12 were given the drug for 3 days postoperatively, and 10 no therapeutic agent. These groups were otherwise comparable. Postoperatively, the control patients had significantly higher levels of total amylase activity in the serum and P-type amylase when compared to the preoperative data. These amylase activities almost remained at the preoperative level in those given the drug. When the ratio of increase in enzyme activities (postoperative value divided by preoperative value) were compared, on the 7th postoperative day, total amylase activity in the serum and P-type amylase were significantly different between the two groups (p < 0.05). This difference was also evident when comparing total amylase activity in the urine (p < 0.05). These findings indicate that prophylactic administration of urinary trypsin inhibitor would aid in preventing postoperative hyperamylasemia caused by R2 gastrectomy in patients with gastric cancer.

ISSN:0014-312X    

DOI:10.1159/000129155

出版商:S. Karger AG    

年代:1991

数据来源: Karger