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M D Menger

Publications and source records attributed to M D Menger.

At least 181 records · Page 10Linked to original sources
PubMed1996

Determinants of pancreatic microcirculation in acute pancreatitis in rats.

The aim of the study was to evaluate the effects of arterial hypotension, high-volume crystalloid resuscitation, and isovolemic hemodilution on pancreatic microvascular perfusion during acute pancreatitis. Using intravital microscopy, pancreatic functional capillary density was analyzed in rats 1 and 2 hr after onset of acute pancreatitis. Pancreatic microvascular perfusion in acute pancreatitis was characterized by a (-62%) significant reduction of functional capillary density predominantly in perinecrotic but also in nonnecrotic tissue (-43%). Pancreatic microvascular perfusion failure was aggravated by arterial hypotension but attenuated by treatment with high-volume crystalloid resuscitation. Isovolemic hemodilution was found superior to high-volume crystalloid resuscitation in maintaining pancreatic functional capillary density and therefore has the best potential in preserving tissue integrity and thereby limiting progression of disease. This study underlines the importance of early fluid resuscitation/hemodilution in patients presenting with acute pancreatitis.

Acute Disease↗
PubMed1996

A new method for the intravital microscopic quantification of hepatic sinusoidal perfusion failure using the dye bisbenzamide H33342.

In hepatic pathology, in vivo assessment of microvascular perfusion failure by intravital microscopic determination of functional sinusoidal density is a time-consuming procedure, which requires accurate identification of blood-flow conditions within each individual sinusoid. Herein we report a new method, which is easily applicable and which allows for rapid analysis of hepatic microvascular perfusion deficits by intravital fluorescence microscopy using Bisbenzamide H33342 staining of hepatocytes (excitation 330-390 nm/emission > 430 nm). To validate this method hepatic microvascular perfusion failure was induced in eight spontaneously breathing, chloralhydrate-anesthetized rats by 90-min left lobar ischemia and reperfusion. For quantitative assessment of hepatocellular bisbenzamide fluorescence intensity, gray levels were determined densitometrically, and the area of positive-stained cells was calculated automatically as percentage of the whole area of observation. Within identical acini (n = 67) area of positive hepatocellular fluorescence was correlated with functional sinusoidal density, i.e, total length of perfused sinusoids per observation area (cm/cm2), which was determined simultaneously by contrast enhancement with sodium fluorescein (450-490/ > 520 nm) using a computer-assisted image analysis system. Postischemic reperfusion was characterized by a marked heterogeneity of nutritive perfusion with a considerable number of nonperfused sinusoids. Visualization of bisbenzamide fluorescence revealed brightly stained hepatocytes in well-perfused areas, but faint hepatocellular fluorescence in areas presenting with sinusoidal perfusion failure. Linear regression analysis between area of positive hepatocellular fluorescence and functional sinusoidal density revealed a significant (P < 0.01) correlation (r2 = 0.926), indicating that automated densitometric analysis of hepatocellular bisbenzamide fluorescence represents a valid method to determine hepatic nutritive perfusion failure in vivo.

Animals↗
PubMed1996

Impact of enalapril on microvascular perfusion and leukocyte adherence in a model of rat liver transplantation assessed by in vivo microscopy.

ACE inhibitors have been proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. In an attempt to investigate this effect in a model of syngeneic liver transplantation in the rat, we compared a control group with an ACE inhibitor treatment group, in which enalapril was given i.v. before and during reperfusion. By means of in vivo microscopy, sinusoidal perfusion rate, permanent leukocyte sticking in sinusoids and postsinusoidal venules, and leukocyte rolling in postsinusoidal venules were assessed. Liver function was evaluated by measuring bile output. The sinusoidal perfusion rate was significantly improved by enalapril treatment. Leukocyte sticking in both sinusoids and postsinusoidal venules was found to be remarkably reduced in enalapril-treated animals; the fraction of rolling leukocytes remained unchanged. Bile output was increased in enalapril-treated animals. These results demonstrated, in a model of rat liver transplantation, that ACE inhibition by enalapril is effective in reducing hepatic ischemia/reperfusion damage as assessed by the leukocyte-endothelium interaction using in vivo microscopy and postreperfusion bile production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

First experience with laparoscopic spine fusion in an experimental model in the pig.

BACKGROUND: We elucidated whether anterior lumbar spine fusion with interbody implants (BAK) can be performed in an experimental model in the pig using a transperitoneal laporoscopic approach. METHODS: In seven animals, a pneumoperitoneum with an intraabdominal pressure of 12 mmHg was induced, and five trocars were placed in the middle, as well as in the left and right lateral aspect of the abdomen. With the use of specially designed instruments, the bifurcations of the aorta and vena cava were prepared. The sacral artery, overlying the anterior aspect of the L5/S1 disc space, was retracted, allowing the exposure of the disc space. A working trocar was then fixed to the spine bodies above (L6) and below (S1) the disc, and instrumentation was completed by destruction of the disc, insertion of distraction plug, and implantation of the BAK cage. X-ray control allowed exact positioning of the cage. RESULTS: There were no major complications during the operative procedure, in particular no bleeding from major blood vessels and no injury to intraperitoneal organs. Cages were implanted in all animals in correct position, as indicated by postoperative X-ray control. CONCLUSIONS: We conclude from our experiments that in the pig model implants for anterior interbody lumbar spine fusion can be inserted successfully using the laparoscopic approach. We propose that the pig model represents an ideal tool for training before applying this operative procedure in men.

Animals↗
PubMed1996

Intravital studies on beneficial effects of warm Ringer's lactate rinse in liver transplantation.

This quantitative in vivo fluorescence microscopy study investigated the impact of warm versus cold Ringer's lactate (RL) graft rinse on various microvascular manifestations of ischemia-reperfusion injury after liver transplantation in the rat. Syngeneic orthotopic liver transplantation, including arterial revascularization, was performed in male Lewis rats following 24 h of cold storage in University of Wisconsin (UW) solution. In one group (n = 8) liver grafts were rinsed with 4 degrees C (cold) RL, whereas in the other group (n = 8) grafts were rinsed with 37 degrees C (warm) RL immediately prior to revascularization. Hepatic microvascular perfusion, leukocyteendothelium interaction, and Kupffer cell activation were quantified 30-90 min after graft reperfusion by direct visualization with intravital fluorescence microscopy. Moreover, biliary excretory graft function was analyzed by determination of bile flow and bile salt excretion during the first 90 min after reperfusion. Compared to grafts rinsed with cold RL, acinar and sinusoidal perfusion were found to be significantly increased after rinsing the grafts with warm RL. The amount of nonperfused acini declined from 18.1% +/- 4.0% to 7.4% +/- 1.6% (P < 0.05), and the total percentage of perfused sinusoids increased from 80.1 +/- 1.4 to 88.4 +/- 1.2 (P < 0.001) after cold and warm rinse, respectively. After rinsing the graft with warm RL, WBC adherence in sinusoids and especially in postsinusoidal venules decreased significantly by 28% (P < 0.001) and 33% (P < 0.001), respectively. Kupffer cell activation was markedly reduced after rinsing with RL at 37 degrees C, as indicated by a decelerated adherence of latex particles injected 80 min after reperfusion. Excretory graft function was dramatically increased following warm RL rinse during the 90-min observation period. Bile flow was enhanced from 1.04 +/- 0.5 to 3.9 +/- 0.8 ml/100 g liver per 90 min (P < 0.01), with a parallel rise in bile salt excretion from 24.3 +/- 5.8 to 128.0 +/- 19.8 mmol/ 100 g liver per 90 min (P < 0.05) when compared to cold RL. These data strongly suggest that rinsing liver grafts with warm RL prior to reperfusion represents a simple and inexpensive way to reduce the incidence of primary graft failure secondary to ischemia and reperfusion injury in liver transplantation.

Animals↗
PubMed1996

Ischemia-reperfusion-induced pancreatic microvascular injury. An intravital fluorescence microscopic study in rats.

With the concept that ischemia-reperfusion injury may contribute to the pathogenesis of acute pancreatitis, we have quantitatively analyzed the pancreatic microcirculation of rats during postischemic reperfusion using intravital fluorescence microscopy. Ischemia to the pancreas of Sprague-Dawley rats (N = 7) was induced by clamping the arteriae gastroduodenalis, lienalis, gastrica sinistra, and gastricae breves for 60 min followed by 120 min of reperfusion. Ischemic conditions were verified by measurement of microvascular hemoglobin oxygenation using reflection spectrophotometry (n = 9). Postischemic reperfusion was characterized by a significant (P < 0.05) reduction of functional capillary density to approximately 69% of baseline (no reflow). Reperfusion-induced inflammatory response was reflected by a marked increase (100-fold; P < 0.01) of the number of permanently adherent leukocytes in postcapillary venules (reflow paradox). Postischemic reperfusion was further associated with increased serum lipase activities, and histomorphological analysis revealed alterations, similar as known in acute interstitial pancreatitis, ie, neutrophil infiltration, interstitial edema, and hemorrhagic lesions. We, therefore, conclude that ischemia-reperfusion- associated events, ie, no reflow and reflow paradox, may be considered as trigger mechanisms in the manifestation of distinct types of acute pancreatitis, in particular posttransplant pancreatitis.

Acute Disease↗
PubMed1996

Xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular reperfusion injury of the liver.

Although reactive oxygen metabolites may play a pivotal role in mediating microvascular reperfusion injury, the source of these radicals is still a matter of controversy. With the use of spectrophotometry and intravital microscopy we studied the role of xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular injury in rats. After 20 min of global hepatic ischemia and splanchnic vascular congestion, followed by 40 min of reperfusion (n = 8), xanthine oxidase activities in hepatic venous (26.9 +/- 4.7 nmol/ml x min) and systemic arterial blood (16.3 +/- 2.5 nmol/ml x min) were found significantly (p < .01) increased when compared with sham-operated controls (6.8 +/- 0.9 and 6.0 +/- 0.8 nmol/ml x min, n = 8). The increase of xanthine oxidase activity was accompanied by oxygen radical-mediated intravascular hemolysis. Intravital microscopy (n = 6) revealed accumulation of leukocytes within the postischemic hepatic microvasculature with stasis in sinusoids (75.9 +/- 8.9 per liver lobule) and adherence to the endothelial lining of postsinusoidal venules (534.7 +/- 125.3 per mm2 endothelial surface). Concomitantly, compromised microvascular reperfusion was characterized by perfusion deficits of individual sinusoids (25.6 +/- 4.0% nonperfused sinusoids). The xanthine oxidase inhibitor allopurinol (50 mg/kg b.wt., orally, n = 6) and the radical scavenger superoxide dismutase (60000 IU/kg b.wt., IV, n = 6) effectively (p < .01) inhibited both sinusoidal leukostasis (16.1 +/- 2.6 and 32.1 +/- 3.1 cells/lobule) and venular leukocyte adherence (247.6 +/- 7.9 and 205.0 +/- 38.0 cells/mm2), and, hence, reduced microcirculatory deteriorations, indicated by the attenuation of sinusoidal perfusion failure (2.8 +/- 0.8 and 9.0 +/- 3.1%). Our results support the hypothesis that portal triad crossclamping-induced microvascular reperfusion injury is triggered by superoxide radicals derived from the xanthine oxidase system.

Allopurinol↗
PubMed1996

Small-volume resuscitation restores hemorrhage-induced microcirculatory disorders in rat pancreas.

OBJECTIVES: Pancreatic hypoxia/ischemia, as a consequence of shock-induced microcirculatory failure, is considered a causative factor in the initiation and/or progression of pancreatic tissue injury. The aim of this study was to compare the effects of "small volume resuscitation" with conventional isovolemic colloid and hypervolemic crystalloid resuscitation on pancreatic microcirculation after hemorrhagic shock. DESIGN: Randomized, controlled intervention trial. SETTING: University laboratory. SUBJECTS: Twenty-three male Sprague-Dawley rats anesthetized with á-chloralose mechanically and ventilated. INTERVENTIONS: Rats subjected to 1 hr of hemorrhagic shock (mean arterial pressure of 40 mm Hg) were resuscitated with lactated Ringer's solution (four-fold shed volume/20 mins), 10% hydroxyethyl starch (shed volume/5 mins), or 7.2% sodium chloride-10% hydroxyethyl starch (10% shed volume/2 mins). MEASUREMENTS AND MAIN RESULTS: The microcirculation of pancreatic acinar tissue was studied by means of intravital fluorescence microscopy and laser Doppler flowmetry. At 1 hr after resuscitation, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux were found to be significantly increased when compared with those values in the shock state. However, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux did not completely return to preshock values, regardless of the type of fluid used for resuscitation. At 15 mins and 1 hr after resuscitation, shock-induced capillary perfusion failure (reduction of functional capillary density) was restored to 91% to 94% of baseline values in all groups. Pancreatic capillary narrowing, indicating microvascular endothelial cell swelling, was abolished by resuscitation with both isotonic hydroxyethyl starch and hypertonic hydroxyethyl starch (p<.05 vs. lactated Ringer's solution). CONCLUSIONS: Despite replacement of only 10% of actual blood loss, small-volume resuscitation with hypertonic hydroxyethyl starch is as effective as the ten-fold volume of isotonic hydroxyethyl starch and, due to prevention of microvascular endothelial cell swelling, superior to the 40-fold volume of isotonic lactated Ringer's solution in regard to restoration of the shock-induced microcirculatory disturbances of rat pancreatic acinar tissue.

Analysis of Variance↗
PubMed1996

In vivo documentation of an arteriovenous shunt in rat pancreatic acinar tissue.

With the use of epiilumination fluorescence microscopy, we demonstrate for the first time in vivo the existence and function of direct arteriovenous communication (arteriovenous shunt) in rat pancreatic acinar tissue. In eight Sprague-Dawley rats the corpus and tail of the pancreatic gland were reviewed for arteriovenous anastomoses. In seven animals the technique did not allow us to visualize completely the arteriolar and venular vascular system due to overlying pancreatic tissue. In one animal, however, the vascular trees could be identified in their continuity over a length of several millimeters, including an arteriovenous shunt with a diameter of 12.0 microns. Analysis of volumetric blood flow revealed that 86.2% (15.61 nl/min) of the arteriolar blood volume was shunted into the venule, while only 13.8% (2.50 nl/min) of the blood volume was carried by the arteriole distal to the arteriovenous shunt to the nutritive capillary bed. There were no changes in diameter, i.e., vasoconstriction, vasodilation, or vasomotion, over an observation period of 30 min, indicating that, at least under physiological conditions, this arteriovenous communication functioned as a real "fare-through" channel.

Animals↗
PubMed1996

Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation.

To study the role of Kupffer cells (KC) as a cellular source of proinflammatory cytokines in hepatic ischemia/reperfusion, Sprague-Dawley rats were subjected to 20 min global hepatic ischemia. Sham-operated animals served as controls. Blood levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interleukin 6 (IL-6) were determined after 10, 30, 60, 120, and 240 min of reperfusion and compared with spontaneous cytokine release by KC isolated after 60 min of reperfusion. Hepatic ischemia/reperfusion resulted in an enhanced (p < .01) spontaneous release of TNF-alpha (+482%), IL-1 alpha (+33%), and IL-6 (+175%) by KC. Kinetic analysis of cytokinemia revealed an early increase (p < .01) of TNF-alpha and IL-1 alpha within minutes upon reperfusion, while an elevation of IL-6 serum levels was observed with a delay of 2 h. Early cytokinemia was associated with dysfunction/injury of the liver, lung, and kidney after 4 and 24 h of reperfusion, respectively. These data indicate that hepatic ischemia/reperfusion results in Kupffer cell activation and increased cytokine levels, which may produce systemic inflammation and may be responsible for tissue injury locally and on remote sites.

Animals↗
PubMed1996

Modulation of kupffer cell activity by gadolinium chloride in endotoxemic rats.

Gadolinium chloride (GdCl3) has been reported to block Kupffer cell (KC) phagocytic activity in rats. In this study, we investigated the action of GdCl3 on Kupffer cells and related effects in response to lipopolysaccharide (LPS) exposure of rats. Using intravital fluorescence microscopy (IVFM), the hepatic microcirculation (phagocytic activity and zonal distribution of KC, sinusoidal perfusion, leukocyte-endothelial cell interaction) of rats pretreated with either saline or GdCl3 (10 mg/kg i.v. for 2 days) was studied at 1 h (n = 14) and 16 h (n = 16) after exposure to Escherichia coli LPS (10 mg/kg i.v.). LPS-exposure (1 h) resulted in KC activation with increased phagocytic activity (IVFM), intracellular enrichment of phagocytic vacuoles, and marked rise of cytokines (tumor necrosis factor-alpha, interleukin-6) in serum, whereas GdCl3-pretreatment completely inhibited the LPS-related KC response. 16 h after LPS-exposure, saline-treated animals revealed high serum levels of LPS, associated with microvascular perfusion deficits, marked KC destruction, and hepatocellular disintegration, which finally resulted in a mortality rate of 47% (7/15). In contrast, none of the GdCl3-treated animals died (0/8). GdCl3-pretreatment significantly attenuated LPS-induced hepatic microvascular perfusion failure and parenchymal cell injury at 16 h after LPS exposure. Intact KC morphology and low serum levels of LPS indicated adequate clearance capacity. Based on these results, we propose that modulation of LPS-induced KC phagocytic activity and KC function by GdCl3 is effective to protect from LPS-induced hepatic injury and systemic toxicity, probably by inhibition of overwhelming inflammatory response.

Animals↗
PubMed1996

Leukocyte stasis in hepatic sinusoids.

There is ongoing debate on the significance of capillary leukostasis for the manifestation of ischemia-reperfusion (I/R)-induced capillary "no-reflow". Using intravital fluorescence microscopy, we studied leukocyte trafficking through the hepatic microvasculature and the relevance of sinusoidal leukostasis for nutritive perfusion failure in rats after hepatic I/R (n = 8). Sham-operated animals (n = 8) served as controls. Hepatic reperfusion was characterized by perfusion failure of individual sinusoids and a significant increase of sinusoidal leukostasis. However, in both nonischemic and postischemic livers, the major fraction of sinusoids presenting with stagnant leukocytes were found perfused (97 +/- 1 and 73 +/- 5%, respectively), whereas only 3 +/- 1 and 27 +/- 5% failed to conduct flow. Analysis of leukocyte trafficking in sinusoids with leukostasis revealed a marked reduction of leukocyte velocity and leukocyte flux in nonischemic and postischemic livers compared with sinusoids without leukostasis. Thus stagnant leukocytes retard cellular passage through hepatic sinusoids, probably due to an increase of flow resistance. However, the fact that during postischemic reperfusion > 70% of the sinusoids accommodating stagnant leukocytes are still perfused indicates that sinusoidal leukostasis per se does not necessarily determine perfusion failure ("no-reflow") after I/R of the liver.

Animals↗
PubMed1996

Systemic and subcutaneous microvascular Po2 dissociation during 4-h hemorrhagic shock in conscious hamsters.

The relationship between systemic and microvascular Po2 in subcutaneous connective tissue and hemodynamics was investigated during 4-h hemorrhagic shock (40 mmHg) in conscious Syrian hamsters (n = 66) fitted with a dorsal skinfold window. Systemic blood gases, metabolic parameters, arteriolar, venular, and tissue Po2, microvascular red blood cell velocity, and blood flow were evaluated in survivors (S) and nonsurvivors (NS). Surviving animals were resuscitated with shed blood. Microvascular and tissue Po2 were measured by phosphorescence decay of Pd-meso-tetra (4-carboxyphenyl) porphyrin (30 mg/kg body wt iv). Shock caused a significant dissociation between systemic arterial and microvascular arteriolar Po2 levels. Arterial Po2 increased from 59.7 +/- 12.0 to 110.8 +/- 19.7 mmHg (S) and from 64.0 +/- 13.7 to 128.5 +/- 10.1 mmHg (NS), whereas Po2 in large arterioles decreased from 56.9 +/- 5.5 (control) to 29.5 +/- 20.1 (S) and 6.0 +/- 5.7 mmHg (NS). Correspondingly, tissue Po2 fell from 24.1 +/- 6.8 (control) to 0.9 +/- 0.6 (S) and 0.4 +/- 0.3 mmHg (NS). Venous Po2 decreased from 28.8 +/- 3.7 to 20.4 +/- 4.1 (S) and from 28.0 +/- 2.9 to 16.3 +/- 0.5 mmHg (NS). Shock outcome and tissue oxygenation were predicted by arterial blood gases and metabolic and microcirculatory conditions but not by central venous Po2.

Animals↗
PubMed1996

[Laparoscopic 2-level fusion of the lumbar spine with Bagby and Kuslich implants].

In a 50-year-old female patient, presenting with permanent low lumbar back pain and intermittent neurological alterations due to degenerative disc disease L4-5 and L5-/S1 we demonstrate that two-level anterior interbody fusion can be performed via laparoscopic transabdominal instrumentation using BAK interbody implants. Intervertebral disc space L5-/S1 was stabilized approaching the spine caudally of the aortic bifurcation, while disc space L4-L5 required an approach from the left lateral aspect, mobilizing the aorta and vena cava to the right. The postoperative course was without complications and allowed discharge from the hospital on day 8. X-ray control 4 months later demonstrated restoration of adequate disc space at L4-L5 and L5-/S1 and appropriate positioning of the implants.

Female↗
PubMed1995

Angiogenesis and vascularization of murine pancreatic islet isografts.

Although the microvascular endothelium has been identified as the primary target site for the initiation of pancreatic islet graft rejection, little is known of the microvascular and cellular mechanisms involved, partly due to the lack of adequate models. Herein, we present a model for the in vivo assessment of the microcirculation of pancreatic islet grafts in mice. Isolated islets of Langerhans from immunocompetent hairless mice and immunoincompetent athymic nude mice were transplanted syngeneically into a specially designed dorsal skinfold chamber mounted on nondiabetic recipients. The islets' microcirculation was visualized by means of intravital fluorescence microscopy, and microcirculatory parameters were quantitatively analysed over a period of 14 days in the awake animal. Between day 2 and 4 after transplantation 84% (31/37; hairless mice) and 69% (36/52; nude mice) of the islet grafts revealed capillary sprouts and formation of new microvessels. On day 6, these sprouts were found interconnected, and red blood cell movement within the newly formed microvascular network was observed. The process of angiogenesis and revascularization was completed within 10 days after transplantation yielding a glomerulus-like network of capillaries as known for pancreatic islets in situ. Functional capillary density of the islet grafts ranged between 650 and 700 cm-1 in both hairless and nude mice. Within the islets' microvessels neither accumulation of leukocytes nor leukocyte-endothelial cell interaction was observed, indicating the lack of rejection and inflammation in these syngeneic islet grafts. We propose that this model provides a wide spectrum of promising experimental approaches for the study of microcirculatory and cellular mechanisms in free pancreatic islet transplantation.

Animals↗
PubMed1995

In vivo evidence that intercellular adhesion molecule-1 does not mediate endotoxin-induced hepatic leukocyte-endothelial cell interaction.

BACKGROUND/AIMS: We have previously demonstrated that endotoxemia induces an immediate leukocytic response within the hepatic microvasculature, with leukostasis in sinusoids and leukocyte adherence in post-sinusoidal venules. We have now studied the role of intercellular adhesion molecule-1 in endotoxin-induced hepatic leukocyte-endothelial cell interaction in vivo using fluorescence microscopy. METHODS: Sprague-Dawley rats were pretreated with either 1 mg/kg (n = 5) or 2 mg/kg (n = 4) of a monoclonal anti-rat anti-intercellular adhesion molecule-1 antibody intravenously, followed by exposure to endotoxin (E. coli LPS 10 mg/kg iv). Animals pretreated with an isotype-matched IgG1 control antibody (n = 5) served as controls. Intravital fluorescence microscopy for analysis of the hepatic microcirculation was performed prior to and 1 h after lipopolysaccharide exposure. RESULTS: At 1 h after lipopolysaccharide-exposure, control animals showed a marked reduction of systemic leukocyte count, which was associated with a significant (p < 0.01) hepatic microvascular accumulation of leukocytes with stasis in sinusoids, as well as rolling and adherence in postsinusoidal venules. Pretreatment with anti-intercellular adhesion molecule-1 was not effective in preventing either systemic leukopenia or intravascular sequestration of leukocytes in endotoxemic livers. CONCLUSIONS: Intercellular adhesion molecule-1 does not mediate endotoxin-induced early leukocytic response within the hepatic microcirculation.

Animals↗
PubMed1995

Leukocytes contribute to hepatic ischemia/reperfusion injury via intercellular adhesion molecule-1-mediated venular adherence.

BACKGROUND: Leukocytes are suggested to modulate ischemia/reperfusion injury via membrane receptor-controlled interaction with the microvascular endothelium. METHODS: With the use of intravital fluorescence microscopy we investigated the role of the intercellular adhesion molecule-1 (ICAM-1) in a rat model of hepatic reperfusion injury with a neutralizing monoclonal antibody (anti-ICAM-1). RESULTS: Sixty minutes of left lobar ischemia and reperfusion (isotype-matched immunoglobulin G1 control antibody) caused leukostasis in sinusoids (240 +/- 15 cells per liver lobule), leukocyte adherence in postsinusoidal venules (679 +/- 76 cells per mm2 endothelial surface of postsinusoidal venules), nutritive perfusion failure (15% +/- 2% nonperfused sinusoids), excretory dysfunction (bile flow, 1.2 +/- 0.3 microliters.min-1.gm-1), and loss of hepatocellular integrity (serum aspartate aminotransferase, 1353 +/- 317 units.L-1; serum alanine aminotransferase, 1055 +/- 265 units.L-1). Anti-ICAM-1 did not affect sinusoidal leukostasis; however, it effectively inhibited postischemic leukocyte adherence to the venular endothelial lining (217 +/- 38 cells/mm2, p < 0.01). Concomitantly, hepatic reperfusion injury, including sinusoidal perfusion (6% +/- 1% nonperfused sinusoids, p < 0.01), excretory function (bile flow, 1.8 +/- 0.1 microliters.min-1.gm-1, p < 0.05), and hepatocellular integrity (aspartate aminotransferase, 480 +/- 108 units.L-1; alanine aminotransferase, 447 +/- 80 units.L-1, p < 0.05), was significantly ameliorated by anti-ICAM-1. CONCLUSIONS: These findings prove in vivo the pivotal role of ICAM-1 in leukocyte-dependent manifestation of postischemic liver damage.

Animals↗