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S Post

Publications and source records attributed to S Post.

At least 73 records · Page 4Linked to original sources
PubMed1994

Short-term T cell receptor directed immunotherapy induces organ specific peripheral tolerance in a strongly incompatible rat model.

We analysed the effect of selective alpha/beta-T cell elimination on allograft survival in a strongly histoincompatible DA-->LEWIS rat model by treatment of recipients with the mouse monoclonal antibody R73 two times before and seven times after transplantation. R73 induced virtually indefinite cardiac allograft survival in 44% of six-week-old LEWIS recipients, whereas donor-type skin allografts were rejected within 11 days. The remaining 56% of animals presented a mean cardiac survival time of 41 +/- 13 days. Graft prolongation was age dependent since in ten-week-old animals the survival time was only of 19 +/- 5 days (untreated controls: 7 +/- 1 days). R73 induced a rapid decrease of R73-positive T cells in the peripheral blood from 70% before treatment to 2%. From the fifth day of treatment a gradual T cell recovery was registered. The T cell marker CD5 decreased from 72% to 17% but recovered already from the second day of treatment. Determination of alpha/beta-TCR, CD3 and CD5 density on T cells during R73 therapy showed that the initial T cell decrease was due to T cell elimination, whereas modulation of alpha/beta-TCR was predominant during the following days. Anti-R73 antibodies appeared regularly during the first week of treatment and blocked R73 activity, indicating their anti-idiotypic nature. The present findings show that short-term R73 therapy is able to induce long-lasting allograft survival. This experimental model can be used to study the basis of peripheral organ specific T cell tolerance.

Animals↗
PubMed1994

Depressed phagocytic activity of Kupffer cells after warm ischemia-reperfusion of the liver.

Phagocytic activity of Kupffer cells following hepatic ischemia/reperfusion was studied in 39 livers of male Sprague-Dawley rats by in vivo fluorescence microscopy. Animals were subjected to either 20 min (group B, n = 9) and 60 min left hepatic lobar ischemia (group C, n = 9) or to 20 min of global hepatic ischemia (group D, n = 11). Sham-operated animals without ischemia served as controls (group A, n = 10). After 60 min postischemic reperfusion, fluorescent latex beads (3 x 10(8).kg body wt-1; diameter: 1.1 microns) were injected intra-arterially. The zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. After 20 min of left hepatic lobar ischemia, 50%, 38% and 12% of injected latex beads adhered in zones 1, 2 and 3, respectively, and did not significantly differ from control livers (group A: 57%, 32% and 11%). In contrast, after 60 min of left hepatic lobar ischemia (group C) as well as after 20 min of global hepatic ischemia (group D), a more homogeneous distribution of latex beads adherent in zones 1, 2 and 3 was observed (group C: 48%, 36% and 16%; group D: 48%, 36% and 16%). Kinetic analysis of phagocytosis (% adherence of visible latex beads 1 min and 3 min after injection) showed no significant difference between 20 min left hepatic lobar ischemia (group B: 84% and 95%) and control (group A: 81% and 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Ischaemic preconditioning by partial occlusion without intermittent reperfusion.

OBJECTIVE: The aim was to investigate whether ischaemic preconditioning can be obtained by a partial coronary artery occlusion without intermittent reperfusion. METHODS: In seven anaesthetised open chest pigs, the flow in the proximal left anterior descending coronary artery was reduced to 30% of baseline during 30 min before the vessel was occluded completely for 60 min (60 min total coronary occlusion, TCO). After 2 h of reperfusion, the area at risk (AR) and infarct size (IS) were determined using standard procedures. Infarct sizes were compared to those observed in control animals (n = 12), which were subjected to 60 min TCO and 2 h reperfusion, and to infarct sizes determined in animals preconditioned by 10 min TCO with either 15 min (n = 10) or 60 min (n = 5) of reperfusion before the 60 min TCO and 2 h reperfusion. In the last three groups of animals, area at risk was varied by occluding the coronary artery or its branches at different sites. RESULTS: In the control animals infarct size was linearly related (r = 0.99, p < 0.001) to the area at risk with a positive intercept on the AR axis: IS/LVmass (x100%) = 0.88 AR/LVmass (x100%)-3.6. At comparable areas at risk, the infarct size of the animals preconditioned with a 10 min TCO was less than for the control animals. For the animals preconditioned with 10 min TCO and 15 min reperfusion, the relationship between infarct size and area at risk was again linear (r = 0.88) and also had a positive intercept on the AR axis: IS/LVmass (x100%) = 0.68 AR/LVmass (x100%)-4.8. All animals with the flow reduction to 30% of baseline immediately preceding the 60 min TCO had infarct sizes smaller (p < 0.05) than predicted from the regression equation for the control animals, but the infarct size limitation could not be simply related to variables such as changes in regional systolic and postsystolic segment length shortening, ATP, or ADP during the partial occlusion period. CONCLUSIONS: Myocardium can be preconditioned with a flow reduction to 30% of baseline for 30 min without intermittent reperfusion (two stage Harris model). The positive intercept on the AR axis of the IS-AR relationship warrants caution of the use of IS/AR as an index for infarct size limitation.

Animals↗
PubMed1994

Timing of arterialization in liver transplantation.

OBJECTIVE: This study analyzed the pathophysiologic sequela of different modes of graft reperfusion in liver transplantation. SUMMARY BACKGROUND DATA: The grafted liver may be reperfused either immediately after completion of portal anastomosis followed by delayed arterial reconstruction or simultaneously by portal and arterial blood if all vascular anastomoses are completed during the anhepatic period. METHODS: Delayed arterialization, that is, arterial reperfusion 8 minutes after portal revascularization (n = 12), was compared with simultaneous arterialization (n = 8) using the model of syngeneic orthotopic liver transplantation in male Lewis rats. After cold storage for 24 hours in University of Wisconsin (UW) solution, intravital fluorescence microscopy was employed 30 to 90 minutes after reperfusion to assess hepatic microvascular perfusion, leukocyte accumulation, and phagocytic activity of Kupffer cells. RESULTS: Compared with delayed arterialization, the number of both nonperfused acini and nonperfused sinusoids was reduced after simultaneous reperfusion by 71% (p = 0.008) and 78% (p < 0.001), respectively. Leukocyte accumulation in sinusoids and postsinusoidal venules after simultaneous arterialization decreased by 17% (p = 0.01) and 64% (P < 0.001), respectively. In addition, simultaneous revascularization was able to attenuate Kupffer cell activation, indicated by significantly slower adherence of latex beads injected 80 minutes after reperfusion. Improved hepatocellular excretory function after simultaneous arterialization was demonstrated by increased bile flow during the observation period of 90 minutes after reperfusion (2.24 +/- 0.7 vs. 0.95 +/- 0.4 mL/100 g liver [mean +/- SEM], p < 0.05). CONCLUSIONS: Timing of arterial reperfusion in liver transplantation may be of critical importance in the prevention of various manifestations of reperfusion injury.

Animals↗
PubMed1994

Effects of warm Carolina rinse on microvascular reperfusion injury in rat liver transplantation.

Recently, it has been demonstrated that the use of both cold Carolina rinse (CR, 4 degrees C) as well as warm Ringer's lactate (RL, 37 degrees C) attenuates microvascular perfusion failure and leukocyte (WBC) accumulation in liver grafts. The aim of this study was to analyse in vivo whether warming of CR can also lead to a reduction in microvascular reperfusion injury in rat liver transplantation. Syngeneic orthotopic liver transplantation, including arterial reconstruction, was performed in male Lewis rats (180-300 g). Livers were stored in University of Wisconsin (UW) solution for 24 h and rinsed with 15 ml CR which was either cold 4 degrees C (n = 7) or warm 37 degrees C (n = 8) prior to reperfusion. Hepatic microcirculation and WBC accumulation were assessed by intravital fluorescence microscopy, and graft function was determined by analysis of bile flow during the 90-min reperfusion period. Warm CR yielded significantly (P < 0.01) improved sinusoidal perfusion when compared with cold CR; however, the extent of WBC adherence in both sinusoids and postsinusoidal venules did not vary between the groups. In addition, bile flow was slightly increased after warm CR. We conclude that after 24 h of cold storage in UW solution, warming of CR may offer additional benefit in the prevention of microcirculatory reperfusion injury without affecting WBC accumulation.

Adenosine↗
PubMed1994

Prolonged rat allograft survival induced by temporary elimination of alpha/beta T cells with monoclonal antibody.

We tested the ability of lewis (LEW; RT-1(1)) recipients to reject DA (RT-1av1) cardiac allografts following the selective elimination of alpha/beta T cells with the mouse monoclonal antibody R73. One group of adult rats (6 weeks old) received 1000 microg R73 i.p. on days 2 and 1 before transplantation, and 100 microg R73 every third day after transplantation up to day 18. Prolonged cardiac graft survival was noted (30, 30, 32, 51, 62, 108, > 500, > 500, > 500 days). Untreated controls (n = 10) rejected their grafts within 7 +/- 1 days. R73 therapy induced a dramatic decrease in alpha/beta T cells from 69% before treatment to 5% within the first 5 days, followed by an increase to 64% by day 8. The T cell increase was paralleled by the appearance of anti-mouse antibody. A second group of adult rats (10 weeks old) received the same treatment. These "older" recipients rejected their grafts within 20 +/- 5 days. Chronic R73 therapy from birth until the day of transplantation (100 microg R73 i.p. twice a week) resulted in graft survival of 37 +/- 9 days in eight animals. Two rats had a graft survival of more than 200 days. When chronic R73 therapy was continued to day 70 after transplantation, DA hearts were accepted well in all animals for more than 100 days. Alpha/beta T cells were virtually absent throughout the whole time of treatment. Antibodies against R73 were not detected. We concluded that selective elimination of alpha/beta T cells has a strong effect on allograft survival.

Age Factors↗
PubMed1994

Heart allograft survival in rats following immunization with soluble peptide MHC class I donor antigens: evidence for the role of indirect recognition in rejection.

The current series of experiments addressed the question of whether indirect priming with donor MHC antigens affects heart allograft survival. LEW (RT-1(1)) rats were immunized with a mixture of two peptides corresponding to the variable region of MHC class I locus Aa antigen (alpha1 and alpha2 domain). The recipients were transplanted with a DA (RT1-1a) heart 1 month after immunization, and graft survival was closely monitored by ECG. All peptide-treated recipients presented with anti-peptide antibodies at the time of transplantation and developed a strongly accelerated graft rejection. These findings indicated that indirect recognition of MHC I donor antigens promotes heart allograft rejection.

Amino Acid Sequence↗
PubMed1994

Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion.

Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of sinusoidal perfusion and decrease of erythrocyte flux, indicating the decisive role of microvascular perfusion failure for the manifestation of hepatic tissue damage and liver dysfunction.

Alanine Transaminase↗
PubMed1994

[Shunt surgery in portal hypertension. Pathophysiology and indications].

Portosystemic shunts are well established methods of avoiding recurrent hemorrhage from esophageal varices. Hemodynamic aspects and clinical results suggest that distal splenorenal shunts should be preferred over non-selective shunts. The functional capacity of the liver is crucial for any type of shunt. In patients with Child C cirrhosis, mortality is known to be particularly high following an emergency shunt so that, this procedure is recommended only as a rescue operation. Although prophylactic shunting decreases the risk of bleeding from varices, it leads to higher liver-related mortality. Prophylactic shunts are, therefore, indicated only in exceptional cases.

Catheterization↗
PubMed1993

Effects of Carolina rinse and adenosine rinse on microvascular perfusion and intrahepatic leukocyte-endothelium interaction after liver transplantation in the rat.

Flushing hepatic grafts immediately before revascularization with a specially designed rinse solution such as "Carolina rinse" has been reported to improve survival after liver transplantation in the rat. This study investigated the influence of Carolina rinse and adenosine rinse on early graft function, microcirculation, and leukocyte (WBC)-endothelial cell interaction of arterialized syngeneic orthotopic liver transplants in Lewis rats. Livers were preserved for 24 hr in University of Wisconsin solution and flushed immediately before reperfusion with either Ringer's lactate (group A: n = 7), Ringer's lactate + 0.2 mmol/liter adenosine (group B: n = 6), or Carolina rinse (group C: n = 7). Microvascular perfusion and WBC accumulation were assessed by intravital fluorescence microscopy. In group C, acinar perfusion was significantly improved, accompanied by a lower percentage of nonperfused sinusoids 1 hr after reperfusion (mean +/- SEM: 26 +/- 2% [group A], 21 +/- 2% [B], 11 +/- 1% [C], P < 0.01 for C vs. A or B). In addition, Carolina rinse and, to a lesser extent, adenosine rinse reduced the number of WBC sticking in sinusoids and postsinusoidal venules. Better graft function in group C was indicated by increased bile flow during the observation period of 90 min after reperfusion (0.5 +/- 0.3 ml/100 g liver [group A], 1.5 +/- 0.7 [B], 3.7 +/- 0.6 [C], P < 0.01 for C vs. A or B). We conclude that Carolina rinse is able to improve early excretory hepatocellular function, microvascular perfusion, and intrahepatic WBC accumulation after prolonged cold ischemia and reperfusion, but adenosine is unlikely to be the key component of this rinse solution.

Adenosine↗
PubMed1993

Differential impact of Carolina rinse and University of Wisconsin solutions on microcirculation, leukocyte adhesion, Kupffer cell activity and biliary excretion after liver transplantation.

This quantitative in vivo fluorescence microscopy study investigated the relative impact of an optimized rinse solution (warm Carolina rinse) and that of an established storage solution (University of Wisconsin solution) on various pathomechanisms of hepatic reperfusion injury after cold storage. Syngeneic orthotopic, arterialized liver transplantation was performed in male Lewis rats after 24 hr of cold ischemia (n = 24). The four experimental groups differed according to the type of preservation/rinse solution used: University of Wisconsin solution/albumin rinse (group 1), autologous blood (just external cooling)/albumin rinse (group 2), blood/Carolina rinse (group 3) and University of Wisconsin solution/Carolina rinse (group 4). Hepatic microvascular perfusion, leukocyte accumulation and phagocytic activity of Kupffer cells were assessed by means of intravital fluorescence microscopy 30 to 90 min after reperfusion. Disturbances of microvascular perfusion were most pronounced in group 2, markedly reduced by University of Wisconsin solution (group 1) and Carolina rinse (group 3) and minimized by combined use of University of Wisconsin solution and Carolina rinse in group 4. Intrahepatic leukocyte-endothelium interaction in sinusoids and postsinusoidal venules was found to depend on the application of Carolina rinse before reperfusion rather than the use of University of Wisconsin solution during cold storage. Activation of phagocytosis by Kupffer cells was most pronounced in group 1, intermediate in groups 2 and 3 and not noticeable in group 4. Hepatocellular excretory function as assessed on the basis of total bile flow and excretion of bile acids during the first 90 min after reperfusion was found to be improved by application of Carolina rinse, both after storage in blood or in University of Wisconsin solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗