ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—Plasma protein loss during abdominal surgery is a known phenomenon, but its possible pathophysiological relevance has remained unknown. The present study evaluates the effects of albumin Substitution on systemic and local hemodynamics and cellular interactions in the mesenteric microcirculation. Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Plasma protein concentrations, systemic and local hemodynamics were recorded during the follow up period, with or without albumin Substitution. Depending on the time course of plasma protein loss in control experiments, 80% of the calculated protein loss was infused during the first 2 h of surgery, and the other 20% over the following 5 h of intravital microscopy. The control group received a continuous infusion of normal saline. Plasma protein loss was mainly due to loss of albumin. A significant increase in adherent and rolling leukocytes was observed during the course of mesenteric exteriorization, which was almost entirely reversed by albumin replacement. Albumin Substitution led to stabilisation of mean arterial pressure and abdominal blood flow and also attenuated reductions in arterial base excess. Albumin infusions to replace plasma protein loss may be a simple and effective measure to attenuate microcirculatory disturbances and may be of benefit in patients undergoing abdominal surgery.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—G‐protein coupled (GPC) chemoattractants are important neutrophil (PMN) activators in human shock and sepsis, acting in part by increasing cytosolic calcium ([Ca2+]i). Rats are widely used as laboratory models of shock and sepsis, but reports of [Ca2+]iflux in circulating rat PMN are rare. Moreover, the [Ca2+]ivalues reported often differ markedly from human systems. We developed study methods where basal [Ca2+]ivalues in circulating rat PMN were comparable to human PMN, but rat PMN still mobilized calcium poorly after stimulation. Trauma (laparotomy) did not change rat PMN basal [Ca2+]i, but induced brisk [Ca2+]iresponses to chemokine and lipid mediators that approximated human PMN responses. This was associated with marked loading of microsomal calcium stores. Formyl peptides still mobilized calcium less well in rat than human PMN. Normal rat PMN appear to circulate in a less mature or primed form than human PMN. A very limited injury rapidly converts rat PMN to a more activated phenotype. PMN thus activated act quite similar to human PMN in terms of GPC receptor‐mediated calcium mobilization. Trauma enhances rat PMN responses to GPC agonists at least in part by loading cell calcium stores.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell‐deficient mice (W/Wv), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of125l‐albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/Wvmice was 62% less than that of mast cell sufficient (+/+) animals and similar to +/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D‐PRO2,D‐TRP7,9‐Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured w/wvmice and +/+ animals treated with chymostatin or dpdt‐sp, but was decreased to 65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in injured untreated +/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after acid aspiration. This mast cell activity likely is regulated by the release of substance P.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—Procalcitonin (PCT) has been described as an early and discriminating marker of bacteria‐associated sepsis in patients. However, little is known of its source and actions, especially with regard to its relation to tumor necrosis factor (TNF). TNF is responsible for the release of several other mediators of sepsis e.g., chemokines. We tested the hypothesis that plasma PCT levels during sepsis differ with regard to the degree of TNF availability. Severe hyperdynamic sepsis was induced in baboons (n = 14) by i.v. infusion of liveE. coli(≌2 × 109colony‐forming units/kg) over 2 h. Animals were pretreated 2 h beforeE. colieither with 1 mg/kg humanized anti‐TNF antibody (CDP571) or placebo (Ringer solution). Plasma PCT levels at baseline was barely detectable, but increased to about 4000 pg/mL at 4 h afterE. coliinfusion. Levels were maximal between 8 and 24 h and had returned nearly to baseline at 72 h. Although no TNF could be measured in the treated group, PCT levels were not different between the placebo and the TNF antibody treatment group. We conclude that PCT levels are not dependent on the systemic presence of TNF in anE. colisepsis model in baboons. Such sepsis induced PCT release is clearly different from the previously reported PCT release during infusion of rhTNF in volunteers or chimpanzees.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—Translocation of luminal bacteria and their products through the intestinal mucosa during ischemiareperfusion (I/R) may modify I/R injury. To test this hypothesis, 16 germ‐free pigs were studied prior to and after clamping the superior mesenteric artery (SMA) and 12 pigs served as controls. Nine pigs in the I/R and 5 in the control group received endotoxin intragastrically, 60 min before baseline. Gut absorption of an inert indicator (polyethyleneglycol [PEG] 3350), gut intraluminal PCO2(tonometry), and systemic and regional hemodynamic variables were measured up to 4 h after baseline. Gut blood flow was stopped during clamping, some reactive hyperemia occurred up to 30 min after declamping in the I/R groups, independently of prior endotoxin administration. Gut intraluminal‐arterial PCO2gradients were elevated in I/R versus control groups during I and for some time during R, prior endotoxin had no effect. However, in controls without and with luminal endotoxin, PEG urinary excretion, as percentage of the dose administered, was 0.12 ± 0.12 and 0.17 ± 0.07, respectively, while it measured 1.82 ± 0.70 in the I/R group and 0.55 ± 0.37% in the I/R and endotoxin groups, respectively (P< 0.001). The data suggest that gut luminal endotoxin ameliorates I/R injury of the gut wall in germ‐free pigs, without altering changes in gut perfusion adequacy and systemic hemodynamics.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—Changes in Ca2+‐induced Ca2+release in cardiac sarcoplasmic reticulum (SR) during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The45Ca2+release studies show that the amount of Ca2+released from the passively and the actively loaded SR vesicles was unaffected during the early sepsis (9 h after CLP), but it was significantly decreased during the late phase (18 h after CLP) of sepsis. The [3H]ryanodine binding assays reveal that the Bmaxfor ryanodine binding was unaffected during the early phase, but was decreased by 32.1% during the late phase of sepsis. The affinity of ryanodine receptor for Ca2+remained unchanged during sepsis. ATP, AMP‐PCP, and caffeine stimulated binding, while MgCI2and ruthenium red inhibited [3H]ryanodine binding in control, early sepsis, and late sepsis groups. The EC50and IC50values for these regulators were unaffected during the progression of sepsis. Digestion of control SR with phospholipase A2decreased [3H]ryanodine binding and the decrease was reversible by the addition of phosphatidylcholine (PC), phosphatidylethanolamine (PE), or phosphatidylserine (PS). Addition of PC, PE, or PS to the SR isolated from septic rats stimulated [3H]ryanodine binding. These data demonstrate that Ca2+‐induced Ca2+release from cardiac SR remained relatively unaffected during the early phase, but was significantly impaired during the late phase of sepsis. The sepsis‐induced impairment in SR Ca2+release is a result of a quantitative reduction in the number of Ca2+release channels. Furthermore, the reduction is associated with a mechanism involving a modification of membrane lipid profile in response to certain stimuli such as activation of phospholipase A2+.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—Chronic sepsis leads to an impaired intestinal microcirculation, which might reflect altered microvascular control. We hypothesized that intestinal microvascular sensitivity to norepinephrine (NE) is decreased during chronic sepsis. Chronic sepsis was induced by a polymicrobial inoculation of implanted subcutaneous sponges in rats. Septic rats were studied either 24 or 72 h after a single inoculation (1‐hit) of bacteria. Other rats received a second inoculation (2‐hit) of bacteria 48 h later and were studied at 24 h after the second inoculation. NE (0.01‐1.0 &mgr;M) responses in the non‐absorbing terminal ileal arterioles (inflow A1, proximal‐p and distal‐d premucosal A3) were measured by video microscopy. NE threshold sensitivity (pDT20= ‐log of 20% response dose) was analyzed. pDT20was significantly decreased in A1, pA3and dA3of 1‐hit 24‐h septic rats (P< 0.05), and was further decreased in all vessels of 2‐hit 72‐h septic rats (P< 0.05). In contrast, the pDT20of all three vessels significantly returned toward normal values after 72 h in rats that had only 1 bacteria inoculation. We conclude that an initial bacterial challenge decreases vasoconstrictor reactivity of the intestinal microcirculation and that subsequent repeated bacterial challenge exacerbates this defect in vasoconstrictor control in the non‐absorbing intestine.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—While there is a growing body of evidence suggesting that hypercholesterolemia prior to the onset of atherosclerosis renders tissues more susceptible to inflammation, the mechanisms that underlie this exaggerated inflammatory response remain poorly defined. The overall objective of this study was to assess the influence of hypercholesterolemia on endotoxin‐induced endothelial cell adhesion molecule (CAM) expression in different vascular beds. Another objective was to determine whether the altered endothelial CAM expression in hypercholesterolemic animals is associated with a corresponding change in plasma cytokine levels. Male Sprague/Dawley rats (SD) were placed either on a normal (control) or high cholesterol (HC) diet for 3 weeks. The dual radiolabeled monoclonal antibody (mAb) technique was used to measure the expression of P‐selectin, E‐selectin, ICAM‐1, and VCAM‐1 in different vascular beds after intraperitoneal injection of endotoxin (LPS) derived from Salmonella abortus equi. LPS induced a significant increase in the expression of all endothelial CAMs in both normocholesterolemic and hypercholesterolemic groups. However, hypercholesterolemia enhanced LPS‐induced expression of P‐selectin, E‐selectin, and ICAM‐1 in several vascular beds, while VCAM‐1 expression was unaffected. Thrombocytopenia, induced with anti‐platelet serum, did not alter LPS‐induced P‐selectin expression in either group, suggesting that platelets do not contribute to this response. Hypercholesterolemia was associated with an exaggerated increase in plasma TNF‐&agr;, but not IL‐1&bgr;, after LPS treatment. These results indicate that hypercholesterolemia in rats may render tissues more vulnerable to the inflammatory effects of LPS by enhancing the expression of certain endothelial CAMs.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ABSTRACT—In the present study, by comparing the responses in wild‐type mice (+/+) and mice lacking (−/−) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of non‐septic shock. A severe inflammatory response characterized by peritoneal exudation, high peritoneal levels of nitrate/nitrite, and leukocyte infiltration into peritoneal exudate was induced by zymosan administration in iNOS +/+ mice. This inflammatory process coincided with the damage of lung, liver, and small intestine, as assessed by histological examination. Lung, small intestine, and liver myeloperoxidase (MPO) activity, indicative of neutrophil infiltration and lipid peroxidation, were significantly increased in zymosan‐treated iNOS +/+ mice. Peritoneal administration of zymosan in the iNOS +/+ mice induced also a significant increase in the plasma levels of nitrite/nitrate and in the levels of peroxynitrite at 18 h after zymosan challenge. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine and to poly ADP‐ribose synthetase (PARS) in the lung, liver, and intestine of zymosan‐treated iNOS +/+ mice. The intensity and degree of nitrotyrosine and PARS were markedly reduced in tissue section from zymosan‐iNOS −/− mice. Zymosan‐treated iNOS −/− mice showed a significantly decreased mortality and inhibition of the development of peritonitis. In addition, iNOS −/− mice showed a significant protection on the development of organ failure since tissue injury and MPO were reduced in lung, small intestine, and liver. Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage, and reduction of cellular levels of NAD†was observed inex vivomacrophages harvested from the peritoneal cavity of iNOS −/− mice subjected to zymosan‐induced non‐septic shock.In vivotreatment with aminoguanidine (300 mg/kg 1 and 6 h after zymosan administration) significantly prevents the inflammatory process. Taken together, our results clearly demonstrate that iNOS plays an important role in zymosaninduced non‐septic shock.

ISSN:1073-2322    

出版商:OVID    

年代:2001

数据来源: OVID