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John G. Wood - One of the best experts on this subject based on the ideXlab platform.
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Fructose, but Not Dextrose, Induces Leukocyte Adherence to the Mesenteric Venule of the Rat by Oxidative Stress
Pediatric Research, 2010Co-Authors: Leone F Mattioli, Naomi B Holloway, James H Thomas, John G. WoodAbstract:Recent evidence indicates that fructose is a pro-inflammatory molecule. Oral fructose induces serum and kidney inflammatory intercellular adhesion molecule-1 (ICAM-1) in rats. Fructose also induces ICAM-1 expression in human aortic endothelial cells (HAEC) and monocyte chemoattractant protein-1 in proximal tubular renal cells. It is not known whether fructose may directly promote inflammation on the intestinal microcirculation. Accordingly, using intravital microscopy we studied the effect of topical fructose and dextrose on Leukocyte Adherence to the mesenteric venule of the rat. Leukocyte Adherence was determined during a control period and after fructose was added to the mesentery, in the presence or absence of the NO donor spermine NONO-ate (SNO), and after i.v. injection of the antioxidant lipoic acid (LA). In separate experiments, we examined the effect of topical dextrose on Leukocyte Adherence to the mesenteric venule. Venular shear rate was calculated. Fructose, but not dextrose, induced significant inflammation independent of shear rate. This effect was completely blocked by SNO and LA, suggesting that fructose induces inflammation via reactive oxygen species (ROS) generation. These results suggest that fructose present in formulas may adversely affect the intestinal microcirculation of premature infants and potentially contribute to the pathogenesis of necrotizing enterocolitis (NEC).
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Leukotriene B4 promotes reactive oxidant generation and Leukocyte Adherence during acute hypoxia
Journal of applied physiology (Bethesda Md. : 1985), 2001Co-Authors: Dawn R. S. Steiner, Norberto C. Gonzalez, John G. WoodAbstract:Acute systemic hypoxia produces rapid Leukocyte Adherence in the rat mesenteric microcirculation, although the underlying mechanisms are not fully known. Hypoxia is known to increase reactive oxyge...
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Leukocyte Adherence and sequestration following hemorrhagic shock and total ischemia in rats
Shock, 1999Co-Authors: Ed W Childs, David M Smalley, John G. Wood, Felicia A. Hunter, Laurence Y CheungAbstract:The pathogenesis of generalized microvascular injury following hemorrhagic shock and total ischemia appears to be dependent on Leukocytes interacting with the venular endothelium. The purpose of this study was to compare Leukocyte Adherence and sequestration following hemorrhagic shock with that of total ischemia in the small bowel mesentery of rats. Leukocyte Adherence and sequestration was measured by direct visualization in vivo using intravital microscopy. In addition, sequestration was also quantitated by measuring tissue levels of myeloperoxidase, a marker of Leukocyte infiltration. Mean arterial blood pressure was decreased to 40 mm Hg for 30 min (hemorrhagic shock group). In the total ischemia group, both the superior and inferior mesenteric arteries were clamped for 30 min followed by reperfusion. Hemorrhagic shock (9.4+/-1.5 cell/100 microm) and total ischemia (8.3+/-3 cell/100 microm) caused a statistically significant increases in Leukocyte Adherence 60 min postinsult as compared with controls (.9+/-1.5 cell/100 microm). However, the increase in Leukocyte Adherence appeared earlier and to a greater degree initially following total ischemia. Leukocyte sequestration as measured by intravital microscopy was significant only after total ischemia [(24.6+/-1.7 cell/(100 microm)2; p<.01] and not hemorrhagic shock [3.4+/-.6 cell/(100 microm)2] versus controls [2.2+/-.2 cell/(100 microm)2]. This difference in sequestration was also confirmed by tissue levels of myeloperoxidase. The results of this study suggest that the microvascular response following hemorrhagic shock is different than that of total ischemia, and caution is warranted when extrapolating the experimental results of one to the other.
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Leukocyte Adherence and sequestration following hemorrhagic shock and total ischemia in rats.
Shock (Augusta Ga.), 1999Co-Authors: Ed W Childs, David M Smalley, John G. Wood, Felicia A. Hunter, Laurence Y CheungAbstract:The pathogenesis of generalized microvascular injury following hemorrhagic shock and total ischemia appears to be dependent on Leukocytes interacting with the venular endothelium. The purpose of this study was to compare Leukocyte Adherence and sequestration following hemorrhagic shock with that of total ischemia in the small bowel mesentery of rats. Leukocyte Adherence and sequestration was measured by direct visualization in vivo using intravital microscopy. In addition, sequestration was also quantitated by measuring tissue levels of myeloperoxidase, a marker of Leukocyte infiltration. Mean arterial blood pressure was decreased to 40 mm Hg for 30 min (hemorrhagic shock group). In the total ischemia group, both the superior and inferior mesenteric arteries were clamped for 30 min followed by reperfusion. Hemorrhagic shock (9.4+/-1.5 cell/100 microm) and total ischemia (8.3+/-3 cell/100 microm) caused a statistically significant increases in Leukocyte Adherence 60 min postinsult as compared with controls (.9+/-1.5 cell/100 microm). However, the increase in Leukocyte Adherence appeared earlier and to a greater degree initially following total ischemia. Leukocyte sequestration as measured by intravital microscopy was significant only after total ischemia [(24.6+/-1.7 cell/(100 microm)2; p
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Nitric Oxide Depletion during Acute Hypoxia Causes Leukocyte Adherence to the Rat Mesenteric Venule
Pediatric Research, 1999Co-Authors: Leone Mattioli, John G. Wood, Jennifer S. Johnson, Norberto C. GonzalezAbstract:Nitric Oxide Depletion during Acute Hypoxia Causes Leukocyte Adherence to the Rat Mesenteric Venule
Eike Martin - One of the best experts on this subject based on the ideXlab platform.
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C1-esterase inhibitor and its effects on endotoxin-induced Leukocyte Adherence and plasma extravasation in postcapillary venules.
Surgery, 1999Co-Authors: Werner Schmidt, Eike Martin, Martha Maria Gebhard, Katja Stenzel, Heinfried SchmidtAbstract:Abstract Background: C1-esterase inhibitor (C1-INH) has been shown to have beneficial effects in patients with sepsis. However, the microcirculatory effects of C1-INH during sepsis are unknown. This study investigated the influence of C1-INH on Leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics in postcapillary venules of rat mesentery during endotoxemia. Methods: Thirty-two anesthetized Wistar rats randomly received 1 of 4 treatments: pretreatment with infusion of C1-INH in a concentration of 7.5 U · kg -1 body weight (C1-INH-7.5 group, n = 8) or in a concentration of 15 U · kg -1 body weight (C1-INH-15 group, n = 8) followed by continuous infusion of Escherichia coli lipopolysaccharide (LPS). The LPS group (n = 8) was pretreated with saline solution 30 minutes before LPS infusion. The control group (n = 8) received equivalent amounts of saline infusion. Leukocyte Adherence, red blood cell velocity, and vessel diameters in postcapillary venules of rat mesentery were determined every 60 minutes during a period of 120 minutes using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from mean red blood cell velocity and vessel diameter. Results: LPS infusion induced a decrease in venular wall shear rate and an increase in Leukocyte Adherence and vascular permeability in postcapillary venules of rat mesentery. All microcirculatory disturbances were attenuated by pretreatment with C1-INH, showing no significant difference between the 2 concentrations. Conclusions: Pretreatment with C1-INH attenuates endotoxin-induced Leukocyte Adherence and macromolecular leakage in postcapillary venules of rat mesentery, indicating that complement inhibition might be a therapeutic tool in the treatment of sepsis. (Surgery 1999;125:280-7.)
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Influence of dopexamine on Leukocyte Adherence and vascular permeability during endotoxemia in rat mesenteric venules
Critical Care, 1997Co-Authors: Werner Schmidt, Heinfried Schmidt, Martha Maria Gebhard, A Häcker, Eike MartinAbstract:Dopexamine is a β2-adrenoceptor agonist with dopamine 1 and 2 receptor properties. It was recently shown that dopexamine was able to preserve the hepatic ultrastructure in a porcine sepsis model [1]. It seemed likely that the anti-inflammatory properties of dopexamine were associated with β2-adrenoceptor properties. The Adherence of Leukocytes to the vascular endothelium is an important step in the development of sepsis. The objective of this study was to investigate whether pretreatment with dopexamine could attenuate Leukocyte Adherence to venular endothelium and influence vascular permeability in post-capillary venules of the rat mesentery during endotoxemia.
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Influence of the Platelet-Activating Factor Receptor Antagonist BN52021 on Endotoxin-Induced Leukocyte Adherence in Rat Mesenteric Venules
The Journal of surgical research, 1996Co-Authors: Heinfried Schmidt, Dorothea Ebeling, Harald Bauer, Hubert Böhrer, Martha Maria Gebhard, Eike MartinAbstract:The aim of this study was to investigate the influence of the platelet-activating factor (PAF) antagonist BN52021 on endotoxin-induced Leukocyte–endothelium interactions and on venular microcirculation. The rates of Leukocyte Adherence and changes in red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate were monitored in rat mesenteric venules following intravenous lipopolysaccharide (LPS) exposure (15 mg/kg body wt). The experiments were performed in LPS-treated control animals and in animals pretreated with the PAF receptor antagonist BN52021. LPS exposure induced a marked increase in adherent Leukocytes in the control group compared to the BN52021-pretreated group. Thirty minutes after LPS injection, 6.1 ± 0.8 Leukocytes were adherent to 100 μm of venule in the control group compared to 2.5 ± 0.5 in BN52021-pretreated animals (P< 0.01). The increased Leukocyte Adherence in the control group was accompanied by leukocytopenia. Red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate did not differ between groups, indicating that increased Leukocyte Adherence in the control group was not due to diminished hydrodynamic dispersal forces. The attenuation of Leukocyte Adherence by the PAF receptor antagonist BN52021 suggests that PAF is involved in the mediation of the initial process of Leukocyte sticking to the endothelium after LPS stimulation.
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Ketamine attenuates endotoxin-induced Leukocyte Adherence in rat mesenteric venules.
Critical care medicine, 1995Co-Authors: Heinfried Schmidt, Dorothea Ebeling, Harald Bauer, Alfons Bach, Hubert Böhrer, Martha Maria Gebhard, Eike MartinAbstract:OBJECTIVES To determine the influence of ketamine on endotoxin-induced Leukocyte Adherence and venular microhemodynamics. DESIGN Randomized, controlled trial. SETTING Experimental laboratory. SUBJECTS Thirty male Wistar rats. INTERVENTIONS The rats were pretreated with ketamine (10 mg/kg iv) or 0.9% saline, and both groups were given endotoxin (Escherichia coli lipopolysaccharide; 5 mg/kg iv). The control group received two doses of 0.9% saline. MEASUREMENTS AND MAIN RESULTS The rates of Leukocyte Adherence and changes in microhemodynamics were monitored in rat mesenteric venules, using in vivo video microscopy. The number of adherent Leukocytes was determined on-line in 10-min intervals from 60 mins before until 2 hrs after endotoxin administration. Venular diameters, red blood cell velocity, volumetric blood flow, and the venular wall shear rate were monitored before and at 10, 30, and 60 mins after endotoxin exposure. A 6.3-fold increase in the number of adherent Leukocytes was observed 10 mins after administration of endotoxin when compared with control animals (5.87 +/- 0.69 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .001). This increase remained unchanged for 120 mins. In ketamine-pretreated rats, a 2.6-fold increase in Leukocyte Adherence occurred during the first 20 mins after endotoxin exposure (2.40 +/- 0.46 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .01). However, no difference in the number of adherent Leukocytes between ketamine-pretreated and control animals was found after this 20-min period. In animals of the control group, no increase in Leukocyte Adherence occurred during the entire observation time. Diameters of mesenteric venules did not change after endotoxin exposure in any of the groups. Red blood cell velocity and venular blood flow in the endotoxin-treated groups decreased 10 mins after the injection of endotoxin when compared with controls, but these values did not show any difference when they were compared between ketamine and saline-pretreated animals. Similarly, venular wall shear rate in the endotoxin-treated groups decreased 10 and 30 mins after injection of endotoxin. However, no significant difference occurred between ketamine and saline-pretreated animals. CONCLUSIONS Pretreatment with ketamine attenuates endotoxin-induced Leukocyte Adherence by a shear rate-independent mechanism, suggesting reduced expression of adhesion molecules. These results indicate that ketamine exerts an anti-inflammatory effect, which might be beneficial in septic patients.
Laurence Y Cheung - One of the best experts on this subject based on the ideXlab platform.
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heme oxygenase 1 mrna expression affects hemorrhagic shock induced Leukocyte Adherence
Journal of Trauma-injury Infection and Critical Care, 2003Co-Authors: Michael Moncure, Lijun Chen, Ed W Childs, David M Smalley, Kahdi F Udobi, Laurence Y CheungAbstract:BACKGROUND Hemorrhagic shock-related Leukocyte Adherence to endothelial cells is a key step in microvascular injury-related organ damage. Heme-oxygenase-1 (HO-1) metabolizes heme, a potent cytotoxic agent, to carbon monoxide and biliverdin. We hypothesized that changing HO-1 expression would change Leukocyte Adherence after hemorrhagic shock. METHODS Rats were administered hemin, zinc protoporphyrin, or vehicle 6 hours before surgery. HO-1 expression was determined by reverse-transcriptase polymerase chain reaction in various tissues. Shock was induced in urethane-anesthetized animals by decreasing mean arterial blood pressure to 40 mm Hg for 60 minutes, followed by standard resuscitation measures. Leukocyte Adherence was measured by intravital microscopy in rat mesenteric venules. RESULTS Hemin, hemorrhagic shock, and the combination resulted in significantly increased HO-1 expression, whereas zinc-protoporphyrin (ZNPP) resulted in significantly decreased Leukocyte Adherence. After hemorrhagic shock and hemin administration, Leukocyte Adherence was significantly decreased 60 minutes into resuscitation (7.92 +/- 2.29 vs. 4.84 +/- 0.71 cells/100 microm, p < 0.05) and significantly increased after ZNPP plus shock (14.08 +/- 3.95, p
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Heme-oxygenase-1 mRNA expression affects hemorrhagic shock-induced Leukocyte Adherence
The Journal of trauma, 2003Co-Authors: Michael Moncure, Lijun Chen, Ed W Childs, David M Smalley, Kahdi F Udobi, Laurence Y CheungAbstract:BACKGROUND Hemorrhagic shock-related Leukocyte Adherence to endothelial cells is a key step in microvascular injury-related organ damage. Heme-oxygenase-1 (HO-1) metabolizes heme, a potent cytotoxic agent, to carbon monoxide and biliverdin. We hypothesized that changing HO-1 expression would change Leukocyte Adherence after hemorrhagic shock. METHODS Rats were administered hemin, zinc protoporphyrin, or vehicle 6 hours before surgery. HO-1 expression was determined by reverse-transcriptase polymerase chain reaction in various tissues. Shock was induced in urethane-anesthetized animals by decreasing mean arterial blood pressure to 40 mm Hg for 60 minutes, followed by standard resuscitation measures. Leukocyte Adherence was measured by intravital microscopy in rat mesenteric venules. RESULTS Hemin, hemorrhagic shock, and the combination resulted in significantly increased HO-1 expression, whereas zinc-protoporphyrin (ZNPP) resulted in significantly decreased Leukocyte Adherence. After hemorrhagic shock and hemin administration, Leukocyte Adherence was significantly decreased 60 minutes into resuscitation (7.92 +/- 2.29 vs. 4.84 +/- 0.71 cells/100 microm, p < 0.05) and significantly increased after ZNPP plus shock (14.08 +/- 3.95, p
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The Local Effect of Paf on Leukocyte Adherence to Small Bowel Mesenteric Venules Following Intra-abdominal Contamination
Inflammation, 2000Co-Authors: David M Smalley, Ed W Childs, Laurence Y CheungAbstract:We have previously demonstrated that intra-abdominal contamination increases neutrophil infiltration into the gastrointestinal tract. The purpose of our current study was twofold: 1) to determine if Leukocyte Adherence to the mesenteric microvasculature occurred by local peritoneal contamination or by systemic mechanisms; and 2) to assess the role of platelet activation factor (PAF) in this process. Rats underwent cecal ligation and puncture (CLP), and 4 h after the procedure we used intravital microscopy to visualize the mesenteric microcirculation. Cecal ligation and puncture increased Leukocyte Adherence (22.3 ± 5.5 Leukocytes/100 μm) vs. sham (2.3 ± 0.9, P < 0.05). WEB-2086, a PAF receptor antagonist, prevented this increase (6.47 ± 4.8, P < 0.05). To assess if Leukocyte Adherence was due to topical effects, we performed similar experiments with the small bowel exteriorized. In such cases, CLP did not increase Leukocyte Adherence (1.2 ± 0.8 vs. 1.4 ± 0.9). In addition, topical application of highly diluted fecal matter (1 : 1000) increased Leukocyte Adherence (4.8 ± 1.2) vs. control (0.6 ± 0.3, P < 0.05). Our study demonstrates that Leukocyte Adherence in the mesenteric microcirculation following intra-abdominal contamination is due to direct topical exposure to fecal matter, and it is mediated by PAF.
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Effect of LFA-1β antibody on Leukocyte Adherence in response to hemorrhagic shock in rats
Shock (Augusta Ga.), 2000Co-Authors: Ed W Childs, Michael Moncure, David M Smalley, Jerrihlyn L. Miller, Laurence Y CheungAbstract:The activation and Adherence of Leukocytes to the venular endothelium are critical steps in the pathogenesis of generalized microvascular injury following hemorrhagic shock. Previous studies have shown that the integrins CD11/CD18 play a significant role in this interaction. The purpose of this study is to examine the efficacy of anti-LFA-1β, an antibody to CD11a/CD18, in attenuating Leukocyte Adherence before, during, and after hemorrhagic shock. Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small intestines were examined to quantitate Leukocyte Adherence using intravital microscopy. In sham-operated rats (control), there was minimal to no Leukocyte Adherence throughout the experiment. Hemorrhagic shock resulted in significant Leukocyte Adherence during resuscitation (10.8 ± 1.7 cells/100 μm, P < 0.01) when compared to control. Anti-LFA-1β, when given before hemorrhagic shock, significantly attenuated Leukocyte Adherence during resuscitation (1.1 ± 0.8, P < 0.01) when compared with hemorrhagic shock alone. This protective effect of anti-LFA-1β on Leukocyte Adherence was even demonstrated when it was given during (1.6 ± 0.3, P < 0.01) and 10 min after hemorrhagic shock (5.8 ± 0.4, P < 0.05). These results suggest that anti-LFA-1β may be of potential therapeutic benefit against microvascular injury caused by hemorrhagic shock.
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Effect of WEB 2086 on Leukocyte Adherence in response to hemorrhagic shock in rats.
The Journal of trauma, 2000Co-Authors: Ed W Childs, Michael Moncure, David M Smalley, Jerrihlyn L. Miller, Laurence Y CheungAbstract:BACKGROUND: The pathogenesis of generalized microvascular injury after hemorrhagic shock is known to involve the generation of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]). The release of PAF is manifested in several ways, including by increased vascular permeability, altered vascular reactivity, and increased Leukocyte Adherence to the endothelium. WEB 2086 is a PAF antagonist that has been shown experimentally to improve survival after hemorrhagic shock. The purpose of this study was to examine the efficacy of WEB 2086 in attenuating Leukocyte Adherence before, during, and after hemorrhagic shock. METHODS: After a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 minutes in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small bowel were examined to quantitate Leukocyte Adherence using intravital microscopy. RESULTS: In sham-operated rats (control), there was minimal to no Leukocyte Adherence throughout the experiment. Hemorrhagic shock resulted in a significant increase in Leukocyte Adherence postshock during resuscitation (10.9 +/- 1.8 cells/100 microm, p < 0.01) when compared with controls. WEB 2086, when given before shock, significantly attenuated Leukocyte Adherence (0.1 +/- 0.08 cells/100 microm, p < 0.01) when compared with hemorrhagic shock alone. This effect of WEB 2086 on Adherence could be demonstrated even when it was given during (3.5 +/- 0.9 cells/100 microm, p < 0.01) and 10 minutes into (5.8 +/- 1.1 cells/100 microm, p < 0.05) hemorrhagic shock. CONCLUSION: Our findings suggest that WEB 2086 may be of therapeutic benefit against the microvascular damage sustained after hemorrhagic shock.
Heinfried Schmidt - One of the best experts on this subject based on the ideXlab platform.
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C1-esterase inhibitor and its effects on endotoxin-induced Leukocyte Adherence and plasma extravasation in postcapillary venules.
Surgery, 1999Co-Authors: Werner Schmidt, Eike Martin, Martha Maria Gebhard, Katja Stenzel, Heinfried SchmidtAbstract:Abstract Background: C1-esterase inhibitor (C1-INH) has been shown to have beneficial effects in patients with sepsis. However, the microcirculatory effects of C1-INH during sepsis are unknown. This study investigated the influence of C1-INH on Leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics in postcapillary venules of rat mesentery during endotoxemia. Methods: Thirty-two anesthetized Wistar rats randomly received 1 of 4 treatments: pretreatment with infusion of C1-INH in a concentration of 7.5 U · kg -1 body weight (C1-INH-7.5 group, n = 8) or in a concentration of 15 U · kg -1 body weight (C1-INH-15 group, n = 8) followed by continuous infusion of Escherichia coli lipopolysaccharide (LPS). The LPS group (n = 8) was pretreated with saline solution 30 minutes before LPS infusion. The control group (n = 8) received equivalent amounts of saline infusion. Leukocyte Adherence, red blood cell velocity, and vessel diameters in postcapillary venules of rat mesentery were determined every 60 minutes during a period of 120 minutes using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from mean red blood cell velocity and vessel diameter. Results: LPS infusion induced a decrease in venular wall shear rate and an increase in Leukocyte Adherence and vascular permeability in postcapillary venules of rat mesentery. All microcirculatory disturbances were attenuated by pretreatment with C1-INH, showing no significant difference between the 2 concentrations. Conclusions: Pretreatment with C1-INH attenuates endotoxin-induced Leukocyte Adherence and macromolecular leakage in postcapillary venules of rat mesentery, indicating that complement inhibition might be a therapeutic tool in the treatment of sepsis. (Surgery 1999;125:280-7.)
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Influence of dopexamine on Leukocyte Adherence and vascular permeability during endotoxemia in rat mesenteric venules
Critical Care, 1997Co-Authors: Werner Schmidt, Heinfried Schmidt, Martha Maria Gebhard, A Häcker, Eike MartinAbstract:Dopexamine is a β2-adrenoceptor agonist with dopamine 1 and 2 receptor properties. It was recently shown that dopexamine was able to preserve the hepatic ultrastructure in a porcine sepsis model [1]. It seemed likely that the anti-inflammatory properties of dopexamine were associated with β2-adrenoceptor properties. The Adherence of Leukocytes to the vascular endothelium is an important step in the development of sepsis. The objective of this study was to investigate whether pretreatment with dopexamine could attenuate Leukocyte Adherence to venular endothelium and influence vascular permeability in post-capillary venules of the rat mesentery during endotoxemia.
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Influence of the Platelet-Activating Factor Receptor Antagonist BN52021 on Endotoxin-Induced Leukocyte Adherence in Rat Mesenteric Venules
The Journal of surgical research, 1996Co-Authors: Heinfried Schmidt, Dorothea Ebeling, Harald Bauer, Hubert Böhrer, Martha Maria Gebhard, Eike MartinAbstract:The aim of this study was to investigate the influence of the platelet-activating factor (PAF) antagonist BN52021 on endotoxin-induced Leukocyte–endothelium interactions and on venular microcirculation. The rates of Leukocyte Adherence and changes in red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate were monitored in rat mesenteric venules following intravenous lipopolysaccharide (LPS) exposure (15 mg/kg body wt). The experiments were performed in LPS-treated control animals and in animals pretreated with the PAF receptor antagonist BN52021. LPS exposure induced a marked increase in adherent Leukocytes in the control group compared to the BN52021-pretreated group. Thirty minutes after LPS injection, 6.1 ± 0.8 Leukocytes were adherent to 100 μm of venule in the control group compared to 2.5 ± 0.5 in BN52021-pretreated animals (P< 0.01). The increased Leukocyte Adherence in the control group was accompanied by leukocytopenia. Red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate did not differ between groups, indicating that increased Leukocyte Adherence in the control group was not due to diminished hydrodynamic dispersal forces. The attenuation of Leukocyte Adherence by the PAF receptor antagonist BN52021 suggests that PAF is involved in the mediation of the initial process of Leukocyte sticking to the endothelium after LPS stimulation.
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Ketamine attenuates endotoxin-induced Leukocyte Adherence in rat mesenteric venules.
Critical care medicine, 1995Co-Authors: Heinfried Schmidt, Dorothea Ebeling, Harald Bauer, Alfons Bach, Hubert Böhrer, Martha Maria Gebhard, Eike MartinAbstract:OBJECTIVES To determine the influence of ketamine on endotoxin-induced Leukocyte Adherence and venular microhemodynamics. DESIGN Randomized, controlled trial. SETTING Experimental laboratory. SUBJECTS Thirty male Wistar rats. INTERVENTIONS The rats were pretreated with ketamine (10 mg/kg iv) or 0.9% saline, and both groups were given endotoxin (Escherichia coli lipopolysaccharide; 5 mg/kg iv). The control group received two doses of 0.9% saline. MEASUREMENTS AND MAIN RESULTS The rates of Leukocyte Adherence and changes in microhemodynamics were monitored in rat mesenteric venules, using in vivo video microscopy. The number of adherent Leukocytes was determined on-line in 10-min intervals from 60 mins before until 2 hrs after endotoxin administration. Venular diameters, red blood cell velocity, volumetric blood flow, and the venular wall shear rate were monitored before and at 10, 30, and 60 mins after endotoxin exposure. A 6.3-fold increase in the number of adherent Leukocytes was observed 10 mins after administration of endotoxin when compared with control animals (5.87 +/- 0.69 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .001). This increase remained unchanged for 120 mins. In ketamine-pretreated rats, a 2.6-fold increase in Leukocyte Adherence occurred during the first 20 mins after endotoxin exposure (2.40 +/- 0.46 vs. 0.93 +/- 0.21 adherent cells/100 microns; p < .01). However, no difference in the number of adherent Leukocytes between ketamine-pretreated and control animals was found after this 20-min period. In animals of the control group, no increase in Leukocyte Adherence occurred during the entire observation time. Diameters of mesenteric venules did not change after endotoxin exposure in any of the groups. Red blood cell velocity and venular blood flow in the endotoxin-treated groups decreased 10 mins after the injection of endotoxin when compared with controls, but these values did not show any difference when they were compared between ketamine and saline-pretreated animals. Similarly, venular wall shear rate in the endotoxin-treated groups decreased 10 and 30 mins after injection of endotoxin. However, no significant difference occurred between ketamine and saline-pretreated animals. CONCLUSIONS Pretreatment with ketamine attenuates endotoxin-induced Leukocyte Adherence by a shear rate-independent mechanism, suggesting reduced expression of adhesion molecules. These results indicate that ketamine exerts an anti-inflammatory effect, which might be beneficial in septic patients.
Jeffrey M. Gidday - One of the best experts on this subject based on the ideXlab platform.
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hydroxyethyl starch reduces Leukocyte Adherence and vascular injury in the newborn pig cerebral circulation after asphyxia
Stroke, 2000Co-Authors: Stuart S. Kaplan, Tae Sung Park, Ernesto R. Gonzales, Jeffrey M. GiddayAbstract:Background and Purpose —Hydroxyethyl starch (HES) has beneficial effects on ischemic brain injury; however, its mechanism of action remains unclear. The present study was undertaken to test the hypothesis that HES can attenuate increases in Leukocyte Adherence and vascular permeability in the cerebral vasculature after global cerebral ischemia induced by asphyxia. Methods —Pial venular Leukocyte Adherence and permeability to sodium fluorescein were quantified in anesthetized newborn piglets by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2 hours of reperfusion after global ischemia induced by 9 minutes of asphyxia. Experimental animals received HES after the asphyxial insult (10% HES 257/0.47, 600 mg/kg IV bolus 5 minutes after asphyxia, followed by 600 mg/kg per hour IV drip during reperfusion; n=9). Results —A progressive and significant ( P <0.05) increase in adherent Leukocytes was observed during the initial 2 hours of reperfusion after asphyxia compared with nonasphyxial controls. In this model, vascular injury, as determined by significant ( P <0.05) increases in fluorescein permeability at 2 hours of reperfusion, is largely dependent on adherent Leukocytes. HES significantly reduced ( P <0.05) Leukocyte Adherence at 1 hour and 2 hours of reperfusion and reduced fluorescein permeability at 2 hours. HES did not change hematocrit or alter pial arteriolar diameter. Conclusions —These findings indicate that a vascular anti-inflammatory action may underlie the beneficial effects of HES in global cerebral ischemia secondary to asphyxia. Since this compound is well tolerated by patients, future preclinical and clinical studies may reveal improvements in functional outcome with the early introduction of this or similar agents after perinatal asphyxia or global ischemia.
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Hydroxyethyl Starch Reduces Leukocyte Adherence and Vascular Injury in the Newborn Pig Cerebral Circulation After Asphyxia
Stroke, 2000Co-Authors: Stuart S. Kaplan, Tae Sung Park, Ernesto R. Gonzales, Jeffrey M. GiddayAbstract:Background and Purpose —Hydroxyethyl starch (HES) has beneficial effects on ischemic brain injury; however, its mechanism of action remains unclear. The present study was undertaken to test the hypothesis that HES can attenuate increases in Leukocyte Adherence and vascular permeability in the cerebral vasculature after global cerebral ischemia induced by asphyxia. Methods —Pial venular Leukocyte Adherence and permeability to sodium fluorescein were quantified in anesthetized newborn piglets by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2 hours of reperfusion after global ischemia induced by 9 minutes of asphyxia. Experimental animals received HES after the asphyxial insult (10% HES 257/0.47, 600 mg/kg IV bolus 5 minutes after asphyxia, followed by 600 mg/kg per hour IV drip during reperfusion; n=9). Results —A progressive and significant ( P
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cd18 dependent Leukocyte Adherence and vascular injury in pig cerebral circulation after ischemia
American Journal of Physiology-heart and Circulatory Physiology, 1997Co-Authors: Jeffrey M. Gidday, Tae Sung Park, Ernesto R. Gonzales, Joel W BeetschAbstract:Recent accumulating evidence indicates that Leukocytes contribute importantly to ischemic brain injury. Although large numbers of Leukocytes are present in the ischemic territory of reperfused brain 24-48 h after the ischemic insult, little is known of the acute inflammatory response to cerebral ischemia, particularly regarding the time course and magnitude of Leukocyte Adherence to cerebrovascular endothelium and the functional consequences of such Adherence. To study these issues, we developed an epifluorescence videomicroscopy system for observing and quantifying the dynamic behavior of rhodamine-labeled Leukocytes in the cerebrovascular microcirculation. Anesthetized piglets equipped with closed cranial windows were used in these investigations. During the initial 2 h of reperfusion after 9 min of asphyxia (n = 6), a marked, progressive increase in adherent Leukocytes was noted in cerebral postcapillary venules that was significantly greater in magnitude than that seen in nonasphyxic, time-matched controls (n = 8). A similar response was observed after complete global ischemia of 10 min duration. A significant increase in sodium fluorescein permeability was also measured at 2 h of reperfusion in asphyxic animals. Pretreating a separate asphyxic animal group (n = 7) with a monoclonal antibody to the Leukocyte adhesion glycoprotein complex CD11/CD18 severely attenuated both Leukocyte Adherence and the increase in vascular permeability. These results provide evidence that adherent Leukocytes contribute to disruption of endothelial integrity during early reperfusion after global ischemic insults, the inhibition of which may reduce the vasogenic edema that occurs early during reperfusion after birth asphyxia, stroke, and cardiac arrest.