| 1. |
- Asaduzzaman, Muhammad, et al.
(författare)
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LFA-1 AND MAC-1 MEDIATE PULMONARY RECRUITMENT OF NEUTROPHILS AND TISSUE DAMAGE IN ABDOMINAL SEPSIS.
- 2008
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1540-0514 .- 1073-2322. ; 30, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil-mediated lung damage is an insidious feature in septic patients, although the adhesive mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of the present study was to define the role of lymphocyte function-antigen 1 (LFA-1) and membrane-activated complex 1 (Mac-1) in septic lung injury. Pulmonary edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, and CXC chemokines were determined after cecal ligation and puncture (CLP). Mice were treated with monoclonal antibodies directed against LFA-1 and Mac-1 before CLP induction. Cecal ligation and puncture induced clear-cut pulmonary damage characterized by edema formation, neutrophil infiltration, and increased levels of CXC chemokines in the lung. Notably, immunoneutralization of LFA-1 or Mac-1 decreased CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 64%. Moreover, functional inhibition of LFA-1 and Mac-1 abolished CLP-induced lung damage and edema. However, formation of CXC chemokines in the lung was intact in mice pretreated with the anti-LFA-1 and anti-Mac-1 antibodies. Our data demonstrate that both LFA-1 and Mac-1 regulate pulmonary infiltration of neutrophils and lung edema associated with abdominal sepsis. Thus, these novel findings suggest that LFA-1 or Mac-1 may serve as targets to protect against lung injury in polymicrobial sepsis.
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| 2. |
- Claesson, Jonas, et al.
(författare)
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Evaluation of intestinal preconditioning in a porcine model using classic ischemic preconditioning or lung recruitment maneuvers.
- 2008
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 21:1, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.
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| 3. |
- Cunha Goncalves, Doris, et al.
(författare)
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Cardiovascular effects of levosimendan in the early stages of endotoxemia.
- 2007
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 28:1, s. 71-7
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.
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| 4. |
- Lipcsey, Miklós, et al.
(författare)
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Effect of the Administration Rate on the Biological Responses To A Fixed Dose of Endotoxin in the Anesthetized Pig
- 2008
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 29:2, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 μg kg-1 h-1, which after 1 h was tapered to 0.5 μg kg-1 h-1, and after 2 h to 0.063 μg kg-1 h-1 (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-α, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly. Abbreviations - BE-Base excess; CI-Cardiac index; DO2-Oxygen delivery; Fio2-fraction of oxygen; Hb-Hemoglobin; LVSWI-Left ventricular stroke work index; MPAP-Mean pulmonary arterial pressure; Paco2-Arterial partial pressure of carbon dioxide; Pao2-Arterial partial pressure of oxygen; pH-Potentia Hydrogenii; SEM-Standard error of the mean; Svo2-Venous oxygen saturation
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| 5. |
- Nelson, Axel, et al.
(författare)
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INCREASED LEVELS OF GLYCOSAMINOGLYCANS DURING SEPTIC SHOCK: RELATION TO MORTALITY AND THE ANTIBACTERIAL ACTIONS OF PLASMA.
- 2008
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Ingår i: Shock. - : Biomedical press. - 1540-0514 .- 1073-2322. ; 30, s. 623-627
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Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycans (GAGs) are structurally heterogeneous negatively charged polysaccharides. Endothelial GAGs, also known as glycocalyx, are involved in capillary permeability. In rat venules stimulated with proinflammatory substances ex vivo, the GAG-containing proteoglycan, syndecan-1, is shed from the endothelium. We wanted to investigate if we could trace the same response during septic shock as reflected in the circulating GAG levels. Arterial plasma samples were collected from 18 consecutive septic shock patients admitted to our intensive care unit. Plasma GAGs were measured with an Alcian blue slot binding assay, and syndecan-1 levels were measured with enzyme-linked immunosorbent assay. Effects of GAGs on the antibacterial activity of plasma were assessed by a radial diffusion assay. The median plasma GAG level was significantly higher in the septic shock patients than in matched controls (median [interquartile range], 2.7 mug/mL [1.9 - 4.8 mug/mL] vs. 1.8 mug/mL [1.7 - 2.0 mug/mL]). Furthermore, the GAG levels were significantly higher in nonsurvivors (4.6 mug/mL [3.1 - 8.8 mug/mL], n = 8) than survivors (1.8 mug/mL [1.6 - 2.6 mug/mL], n = 10). The syndecan-1 levels were also increased in the patients compared with controls (246 ng/mL [180 - 496 ng/mL] vs. 26 ng/mL [23 - 31 ng/mL]) and correlated to the cardiovascular Sequential Organ Failure Assessment score. The GAGs inhibited the endogenous antibacterial activity of plasma as well as isolated antimicrobial peptides. The concentrations required were in the same range as the GAG levels measured in the patients. These results show that the GAG levels are increased in septic shock patients, possibly reflecting peripheral endothelial cell damage. We also found that GAGs in relevant concentrations neutralize antimicrobial peptides in plasma.
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| 6. |
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| 7. |
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| 8. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
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Endothelin b receptors preserve renal blood flow in a normotensive model of endotoxin-induced acute kidney dysfunction
- 2008
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322. ; 29:3, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the role of endothelin 1 receptor subtypes in the early renal response to lipopolysaccharide (LPS) during normotensive endotoxemia with acute kidney dysfunction. Endotoxemia was induced in thiobutabarbital-anesthetized rats (n = 9 per group) by infusion of LPS (dosage, 1 mg/kg per hour i.v.). The study groups (1) sham-saline, (2) LPS-saline, (3) LPS-BQ123, (4) LPS-BQ788 and (5) LPS-BQ123 + BQ788 received isotonic saline, the ETA receptor antagonist BQ-123 (dosage, 30 nmol/kg per minute i.v.), and/or the ETB receptor antagonist BQ-788 (dosage, 30 nmol/kg per minute i.v.) before and during 2 h of LPS infusion. Renal clearance measurements, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (Clark-type microelectrodes) were analyzed throughout. Before LPS administration, there were no significant differences between groups in glomerular filtration rate (GFR), RBF, or in cortical (CLDF) and outer medullary perfusion. However, mean arterial pressure (MAP) was elevated in LPS-BQ788 group compared with LPS-BQ123 + BQ788 group (P < 0.05). In saline-treated rats, endotoxin induced an approximate 35% reduction in GFR (P < 0.05), without significant effects on MAP, RBF, or on CLDF and cortical PO2. In addition, LPS increased outer medullary perfusion and PO2 (P < 0.05). The fractional urinary excretion rates of sodium, potassium, and water were not significantly different in LPS-saline group compared with sham-saline group. Neither selective nor combined ETA and ETB receptor blockade improved GFR. In BQ-788-infused rats, endotoxin produced marked reductions in RBF (-18% +/- 4% [P < 0.05]) and CLDF (-18% +/- 2% [P < 0.05]). Similarly, endotoxin decreased RBF (-14% +/- 3% [P < 0.05]) and CLDF (-10% +/- 2% [P < 0.05]) in LPS-BQ123 + BQ788 group. Endotoxin reduced MAP (-22% +/- 4% [P < 0.05]) in BQ-123-treated rats but did not significantly influence MAP in other groups. We conclude that in early normotensive endotoxemia, ETB receptors exert a renal vasodilator influence and contribute to maintain normal RBF.
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| 9. |
- Nitescu, Nicoletta, 1974, et al.
(författare)
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Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats with endotoxin-induced acute kidney dysfunction.
- 2008
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Ingår i: Shock (Augusta, Ga.). - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322. ; 30:2, s. 166-72
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis is associated with an activation of the renin-angiotensin system and causes acute kidney injury. The aim was to examine the effects of a low, nondepressor dose of the selective angiotensin II type 1 receptor antagonist candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8; 7.5 mg kg(-1), i.p.). At 16 h after endotoxin administration, renal clearance experiments were performed in thiobutabarbital anesthetized rats. Study groups (1) sham-saline, (2) LPS-saline, and (3) LPS-candesartan received isotonic saline or candesartan (10 microg kg(-1), i.v.) after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (P(O2); Clark-type microelectrodes) were analyzed during 2 h after drug administration. At baseline, endotoxemic rats showed an approximately 50% reduction in glomerular filtration rate and RBF (P < 0.05), a decline in cortical and outer medullary perfusion, and Po2 (P < 0.05), but no significant alterations in MAP compared with saline-injected controls. Candesartan treatment significantly improved RBF (+40% +/- 6% vs. baseline), cortical perfusion (+18% +/- 3% vs. baseline), and cortical (+19% +/- 7% vs. baseline) and outer medullary (+22% +/- 10% vs. baseline) P(O2) in endotoxemic rats (P < 0.05 vs. LPS-saline). Candesartan did not significantly influence MAP or glomerular filtration rate, whereas filtration fraction was reduced by 27% +/- 5% vs. baseline (P < 0.05 vs. LPS-saline). In conclusion, candesartan, in a dose that did not significantly decrease MAP, caused renal vasodilation and markedly improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest renoprotective effects of candesartan in sepsis.
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| 10. |
- Nygren, Andreas, 1967, et al.
(författare)
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Norepinephrine and intestinal mucosal perfusion in vasodilatory shock after cardiac surgery
- 2007
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322. ; 28:5, s. 536-543
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Tidskriftsartikel (refereegranskat)abstract
- Patients with norepinephrine-dependent vasodilatory shock after cardiac surgery (n = 10) were compared with uncomplicated postcardiac surgery patients (n = 10) with respect to jejunal mucosal perfusion, gastric-arterial PCO2 gradient, and splanchnic oxygen demand/supply relationship. Furthermore, the effects of norepinephrine-induced variations in MAP on these variables were evaluated in vasodilatory shock. Norepinephrine infusion rate was randomly and sequentially titrated to target MAPs of 60, 75, and 90 mmHg (0.25 +/- 0.24, 0.37 +/- 0.21, and 0.55 +/- 0.39 mug/kg per minute, respectively). Data on jejunal mucosal perfusion, jejunal mucosal hematocrit, and red blood cell (RBC) velocity (laser Doppler flowmetry) as well as gastric-arterial PCO2 gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained. Splanchnic oxygen extraction was 71 +/- 16% in the vasodilatory shock group and 41 +/- 9% in the control group (P < 0.001), whereas splanchnic lactate extraction did not differ between the two groups. Jejunal mucosal perfusion (61%; P < 0.001), RBC velocity (35%; P < 0.01), and arterial-gastric mucosal PCO2 gradient (150%; P < 0.001) were higher in the vasodilatory shock group compared with those of the control group. Jejunal mucosal perfusion, jejunal mucosal hematocrit, RBC velocity, arterial-gastric mucosal PCO2 gradient, splanchnic oxygen extraction, and splanchnic lactate extraction were not affected by increasing infusion rates of norepinephrine. In patients with norepinephrine-dependent vasodilatory shock after cardiac surgery, intestinal mucosal perfusion was higher, whereas splanchnic and gastric oxygen demand/supply relationships were impaired compared with postoperative controls, suggesting that intestinal mucosal perfusion is prioritized in vasodilatory shock. Increasing MAP from 60 to 90 mmHg with norepinephrine in clinical vasodilatory shock does not affect intestinal mucosal perfusion and gastric or global splanchnic oxygen demand/supply relationships.
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