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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A survey is given on the clinical relevance of microaggregates in stored blood. Initially the pathophysiology of aggregation led by electrostatic and humoral changes on the surface and membrane of the platelets is presented, and the well known pathomechanisms of embolization as well as the functional pulmonary impact of these emboli are discussed. The ever increasing importance of humoral factors is stressed, the mechanic obstruction of pulmonary capillaries by microaggregates having not that clinical importance as the general opinion in earlier days has been. New therapeutic aspects therefore are mentioned: The blockade of aggregation and the release syndrome by adding aspirin, aprotinin or prostaglandin E 1 to the stored blood, pharmacologically influencing the metabolism of arachidonic acid by inhibiting negative effects of prostaglandins (injecting ibuprofen as inhibitor of thromboxane-synthesis) and stimulating positive prostaglandin effects (infusion of prostacyclin), and finally the application of fibronectin (cryoprecipitates) for increasing the RES-function thus also enhancing the clearance of microaggregates, fibrinogen/fibrin complexes and intestinal serotonin. The latter way only, however, is also clinically feasable. The purely mechanical microfiltration should therefore still be used (3 pints of blood at least, pulmonary damage by trauma, shock or sepsis) and the methods of giving aggregate-poor red cell preparations (buffy coat free or saline washed) should be remembered. For the future one could speculate that more or less complete humoral block might be used in conjunction with a "midi-filtration" (Eckert: 40-100 mu diameter standard blood filter).
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PMID:[Clinical relevance of microaggregates in stored blood]. 665 92

Thromboxane (TX) has been reported to cause mortality in endotoxin or septic shock. Cyclooxygenase inhibition improves survival in gram-negative or gram-positive shock. The exact level in the prostaglandin system of which the protection occurs is unknown. This study was designed to compare the effects of a cyclooxygenase inhibitor (indomethacin, IND) to a thromboxane synthetase inhibitor (IMI) on survival and on the production of Tx and prostacyclin (PGI2) in a clinically relevant rat gram-negative sepsis model. Three groups were studied: 1) control (N = 35) animals received E coli only; 2) IND (N = 35) treated animals received 3 mg/kg IP; 3) IMI (N = 35) treated animals received 30 mg/kg IP. All drugs were given 1 h after an IP injection of E coli (LD70) organisms. In this model only IND significantly improved survival. IND and IMI significantly blocked the production of Tx seen in septic shock. IND blocked PGI2 production whereas IMI increased the production. These results show that Tx may not be important in the irreversible stages of shock. Shunting prostaglandin production to PGI2 with thromboxane synthetase inhibitors needs to be considered when using this group of compounds. The mechanism of protection by IND remains unknown.
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PMID:Thromboxane synthetase inhibitors in septic shock. 668 24

We investigated a rat fecal peritonitis model of acute intraabdominal sepsis in order to evaluate the potential role of arachidonic acid metabolites in septic shock. Immunoreactive TxB2, the stable metabolite of thromboxane A2, and i6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Plasma levels of iTxB2 rapidly increased from nondetectable (ND less than 200 pg/ml) to 1,052 +/- 208 pg/ml, one hour after feces injection. iTxB2 then increased to 1,681 +/- 248 pg/ml at four hours and remained unchanged through six hours. Plasma i6-keto-PGF1 alpha increased from ND to 3,848 +/- 489 pg/ml a one hour. Four hours after feces, i6-keto-PGF1 alpha levels rose to 7, 450 +/- 933 pg/ml then continued to rise to 9,465 +/- 792 pg/ml at six hours. Either essential fatty acid deficiency (arachidonic acid depletion) or indomethacin treatment (cyclo-oxygenase inhibition) significantly decreased (P less than 0.01) the elevation of plasma iTxB2 and i6-keto-PGF1 alpha associated with fecal peritonitis. Thrombocytopenia occurred within six hours after injection of feces and was significantly improved (P less than 0.05) by indomethacin. Elevated fibrin degradation products at six hours (18 +/- 3 micrograms/ml) were significantly reduced in essential fatty acid-deficient (7 +/- 2 micrograms/ml; P less than 0.05) and indomethacin-treated (4 +/- 0.7 micrograms/ml; P less than 0.01) rats. Survival time (8.6 +/- 0.2 hours) was significantly enhanced by essential fatty acid-deficiency (10.2 +/- 0.4 hours; P less than 0.01) or indomethacin treatment (13.3 +/- 0.6 hours; P less than 0.01). These studies show that fecal peritonitis is associated with increased synthesis of thromboxane A2 and prostacyclin and suggest that these arachidonic acid metabolites may play a role in the pathophysiology of septic shock.
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PMID:Thromboxane and prostacyclin production during septic shock. 675 28

The use of prostaglandins is currently undergoing clinical trials in respiratory failure accompanying sepsis. The effect of prostaglandin E1 (PGE1) and prostacyclin (PGI2) infusion on endotoxin-induced lung injury, with attention to interstitial fluid flux (QL), pulmonary vascular pressure (Ppa), leukocytes, platelets, and release of the lysosomal enzyme beta-glucuronidase, was investigated. A chronic lung lymph fistula model in sheep was used. Seven sheep alternately received Escherichia coli endotoxin and endotoxin plus PGE at a dosage of 1 microgram/kg/min. Six sheep received PGI2 (0.2 microgram/kg/min) instead of PGE1. Both PGE1 and PGI2 decreased the pulmonary hypertension and the interstitial edema produced by endotoxin primarily through their vasodilatory properties. Prostacyclin seemed to have an additional membrane-stabilizing effect. A rebound increase in QL, Ppa, and platelets occurred when PGE1 or PGI2 infusion was discontinued.
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PMID:Prostaglandin infusion and endotoxin-induced lung injury. 703 77

In acute hypoxemic respiratory failure of term and near-term neonates, extra- and intrapulmonary right-to-left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation-perfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near-term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO concentration which improved PaO2 varied considerably between patients. Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (+/- SE) PaO2 from 41 +/- 6 to 57 +/- 9 mm Hg (P < 0.05). Optimum NO concentrations determined by dose-response measurements performed during the first 8 hr of NO inhalation were 8-16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report. 756 4

The development of techniques for manipulating nucleic acids and strategies for delivering DNA to humans has made gene therapy a reality. Although mostly focused on genetically based diseases so far, there is every reason to expand the concept to include acquired diseases. Critical illness may be a good target for gene therapy because of the high mortality and need for only transient treatment. Genes can be delivered in vivo using viral vectors (replication-deficient adenovirus and adeno-associated virus most often). Viral vectors have some negatives, mainly the triggering of an inflammatory and an immune response. Nonviral DNA delivery systems include liposomes (cationic or anionic), direct DNA injection, and polycation-DNA-glycoconjugates. Combining liposomes with viral components to deliver plasmids with a transgene may improve efficiency of delivery without causing toxicity. In a model of acute lung injury, in vivo delivery of a vector hyperexpressing the prostaglandin synthase gene using cationic liposomes resulted in increased production of prostaglandin E2 and prostacyclin in the lungs, and protected the lungs from the effects of endotoxin. This end-result demonstrates the feasibility of this approach. A similar rationale for the treatment of sepsis could be used. Other promising therapeutic genes would include those encoding antioxidant enzymes or antiproteases. The logistics for moving to initial studies of gene therapy in critically ill humans have been worked out for other diseases; such steps should expedite the exploration of this new category of therapies.
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PMID:Gene therapy in acute critical illness. 758 73

The study deals with an animal model for the problems of surgical intensive care patients. Following repeated applications of E. coli endotoxin WO 111:B4 under standard conditions, specific hemodynamic and biochemical (TNF, TXA2, PGI2, IL-6, PAF) and morphological (endothelium of the lung) alterations were detected. ARDS patterns induced by the sepsis were analyzed by high-frequency measurement of pressure and flow (385 measurements per breathing cycle). The role of the intestine in sepsis was investigated by ion-selective monitoring of surface potassium activity comparing mucosa and serosa. Every injection of endotoxin was followed by a selective increase of the potassium activity revealing relative ischemia induced by the endotoxin. The profile of the potassium levels on the surface correlates both with the cardiac output and with the prostacyclin levels. The continuous narrowing of the difference between mucosa and serosa, potassium during the period of investigation can be regarded as evidence for pathologic change in permeability fostering the septic course.
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PMID:[Septic shock and multiple organ failure in surgical intensive care. An animal experiment model on the analysis of pulmonary and intestinal dysfunction]. 769 Jan 6

Neonatal group B streptococcal (GBS) sepsis and pneumonia cause lung endothelial cell injury. GBS invasion of the lung endothelium may be a mechanism for injury and the release of vasoactive eicosanoids. Pulmonary artery endothelial cells (PAEC) and lung microvascular endothelial cells (LMvEC) were isolated from neonatal piglets and were characterized as endothelial on the basis of morphology, uptake of acyl low-density lipoprotein, factor VIII staining, and formation of tube-like structures on Matrigel. PAEC and LMvEC monolayers were infected with COH-1 (parent GBS strain), isogenic mutants of COH-1 devoid of capsular sialic acid or all capsular polysaccharide, or a noninvasive Escherichia coli strain, DH5 alpha. Intracellular GBS were assayed by plate counting of colony-forming units resistant to incubation with extracellular antibiotics. All GBS strains invaded LMvEC significantly more than PAEC, showing that the site of lung endothelial cell origin influences invasion. DH5 alpha was not invasive in either cell type. Both isogenic mutants invaded PAEC and LMvEC more than COH-1 did, showing that GBS capsular polysaccharide attenuates invasion. Live GBS caused both LMvEC and PAEC injury as assessed by lactate dehydrogenase release; heat-killed GBS and DH5 alpha caused no significant injury. Supernatants from PAEC and LMvEC were assayed by radioimmunoassay for prostaglandin E2 (PGE2), the stable metabolite of prostacyclin (6-keto-PGF1 alpha), and the thromboxane metabolite thromoxane B2. At 4 h, live COH-1 caused no significant increases in eicosanoids from both PAEC and LMvEC. At 16 h, live COH-1, but not heat-killed COH-1, caused a significant increase in 6-keto-PGF1 alpha greater than PGE2 from LMvEC, but not PAEC. We conclude that live GBS injure and invade the lung microvascular endothelium and induce release of prostacyclin and PGE2. We postulate that GBS invasion and injury of the lung microvasculature contribute to the pathogenesis of GBS disease.
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PMID:Group B streptococci (GBS) injure lung endothelium in vitro: GBS invasion and GBS-induced eicosanoid production is greater with microvascular than with pulmonary artery cells. 780 66

The baboon model of E. coli sepsis illustrates three concepts with respect to the host response and vascular endothelium. First, the endothelium is the primary target. E. coli sepsis is an acute inflammatory disease of the vascular endothelium. Second, the endothelium is not a passive target. Initially it regulates both the inflammatory and coagulopathic aspects of E. coli sepsis through membrane associated regulatory receptor/plasma protein assemblies including protein C/thrombomodulin, activated protein C/protein S, C4bBP/protein S, tissue factor pathway inhibitor/Xa, antithrombin III/glycosaminoglycans. Third, when overridden by inflammatory events, the endothelium can change its anticoagulant phenotype and mount a massive procoagulant fibrinolytic counter-attack on its luminal side through the expression of tissue factor and release of tissue plasminogen activator. Fourth, again when overridden by inflammatory events, the endothelium can change its antioxidant phenotype and produce a "distal" tissue hypoxia on its abluminal side through induction of free radical generation and peroxidation of mitochondrial lipid membranes of those tissues with high metabolic rates. It has become increasingly clear that the so-called anticoagulant systems which act on the proximal factors of the clotting cascade (protein C, TFPI, AT-III, PGI2) also attenuate the amplification of the inflammatory response. Aspects of the mechanism by which this occurs are coming to light. This includes the attenuation of Il-6 response by TFPI and the attenuation of the complement effects by C4bBP/PS. The specifics of these observations in the E. coli sepsis model will be reviewed.
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PMID:Studies on the inflammatory-coagulant axis in the baboon response to E. coli: regulatory roles of proteins C, S, C4bBP and of inhibitors of tissue factor. 783 58

To examine the roles of leukotriene B4 (LTB4) and prostaglandin I2 (PGI2), the metabolites of arachidonic acid found in patients with sepsis, we measured the serum levels of LTB4 and a stable metabolite of PGI2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), in 22 patients with sepsis. Results were analyzed in relation to patients' survival. The serum levels of both LTB4 and 6-keto-PGF1 alpha were significantly higher in patients who died than in those who survived, thus serving as indicators of illness severity. There was a significant correlation between LTB4 and 6-keto-PGF1 alpha levels. The present study suggests that LTB4, a potent leukocyte activator, induces damage to vascular endothelial cells in patients with sepsis, resulting in the excessive production of PGI2 and, consequently, serious illness.
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PMID:Relationship between leukotriene B4 and prostaglandin I2 in patients with sepsis. 785 Feb 55


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