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

Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containing MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A2 and prostacyclin was investigated by the determination of urinary thromboxane B2 and 6-keto-prostaglandin F2 alpha, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary prostaglandin content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions.
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PMID:Fat emulsions containing medium chain triglycerides in patients with sepsis syndrome: effects on pulmonary hemodynamics and gas exchange. 143 May 88

Tumor necrosis factor-alpha (TNF alpha) has been implicated as an endogenous mediator of the cardiovascular manifestations of sepsis and septic shock. We studied the acute effects of a single dose (50 or 200 micrograms/kg) of intravenous recombinant human TNF alpha (rhTNF alpha) on myocardial function in halothane-anesthetized dogs. Regional cardiac dimensions were measured by using sonomicrometry. Intracavitary left ventricular, ascending aortic, and pulmonary artery pressures were measured by use of micromanometers. Cardiac index was determined by means of thermodilution. Myocardial performance was analyzed by assessing changes in the slope of the left ventricular end-diastolic length-stroke work relationship obtained by performing transient vena caval occlusions. Animals were resuscitated by means of normal saline solutions to maintain baseline regional end-diastolic length. Over a 3-hour period of observation, rhTNF alpha decreased systemic vascular resistance index, but the cytokine did not compromise intrinsic myocardial performance. The circulatory response to rhTNF alpha was a hyperdynamic state characterized by tachycardia, augmented cardiac index, and increased intrinsic myocardial contractility (leftward shift of the left ventricular end-diastolic length-stroke work relationship). In addition, rhTNF alpha caused systemic acidosis and increased plasma levels of prostacyclin metabolite (6-keto-prostaglandin F1 alpha). After the dose of rhTNF alpha large volumes of fluid were required to maintain baseline end-diastolic length. We conclude that in the acute setting, rhTNF alpha elicits abnormalities in peripheral vascular tone that are not accompanied by depression of myocardial function.
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PMID:Load-insensitive assessment of myocardial performance after tumor necrosis factor-alpha in dogs. 159 65

Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.
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PMID:Modulators of coagulation. A critical appraisal of their role in sepsis. 162 18

Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia.
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PMID:Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs. 182 93

Excessive production of prostaglandins may be of importance for the development of organ damage in generalized infection. To investigate the role of tumor necrosis factor (TNF) in systemic prostacyclin release in gram-negative septicemia, the plasma concentrations of its stable metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were sequentially measured after intravenous bolus injections of recombinant human TNF (50 micrograms/m2; n = 6) and Escherichia coli endotoxin (2 ng/kg; n = 3) in healthy men. TNF induced a rapid increase in plasma 6-keto-PGF1 alpha from 0.11 +/- 0.01 to 0.44 +/- 0.15 ng/ml after 30 min (P less than .001). Endotoxin also elicited a rise in plasma 6-keto-PGF1 alpha, but peak values were reached only after 90 min (from 0.07 +/- 0.01 to 0.19 +/- 0.04 ng/ml; P less than .002). These results indicate that TNF may serve as an intermediate factor in systemic elaboration of prostacyclin in endotoxemia and gram-negative septicemia.
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PMID:Comparison of the early dynamics of systemic prostacyclin release after administration of tumor necrosis factor and endotoxin to healthy humans. 186 46

Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macrophages become highly activated for enhanced secretory, phagocytic and cidal functions by LPS. Macrophage-derived cytokines are responsible for many of the pathophysiologic consequences of endotoxemia. The arachidonic acid metabolites, prostacyclin and thromboxane A2 likely mediate early hemodynamic dysfunction and the leukotrienes may potentiate tissue ischemia during endotoxemia. Interleukin 1 (IL-1) induces fever and is responsible for the inflammatory cascade, which constitutes the acute phase response. Tumor necrosis factor (TNF), an important proximal mediator of the effects of LPS, acts to initiate events and formation of other molecules that affect shock and tissue injury. Systemic administration of TNF produces most of the physiologic derangements that are associated with endotoxemia and antibodies that are directed against TNF significantly reduce LPS-induced mortality in experimental animals. In response to endotoxins, mononuclear phagocytes express thromboplastin-like procoagulant activity (PCA), which initiates microvascular thrombosis. Both IL-1 and TNF induce PCA expression, creating a positive feedback loop for LPS-induced coagulopathy. A macrophage-derived platelet activating factor contributes to coagulation dysfunction and further stimulates arachidonic acid metabolism. The ultimate consequences of endotoxemia are multiple system organ failure and death. The numerous feedback loops and intertwining cascades of mediators during endotoxemia defy simplistic methods of treatment. The optimal therapy likely involves methods to alter the generation of inflammatory mediators by mononuclear phagocytes.
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PMID:Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis. 192 Feb 54

In vitro production of PGI2 in canine gallbladders subjected to hypovolemic shock and Escherichia coli sepsis was studied to determine whether a precursor above arachidonic acid in the cyclooxyenase cascade might be operative in the production of prostacyclin, which, in turn, may play a role in the pathogenesis of acute acalculous cholecystitis (AC). L-alpha-phosphatidylcholine (LaP), an arachidonic acid precursor, was used as the test agent. LaP did not stimulate PGI2 production from either gallbladder surface in the hypovelimic animals or the mucosa of the septic shock group. However, it did stimulate PGI2 production from the SS serosa compared with controls, 1375 +/- 432 versus 633 +/- 198 pg/cm2/min (P less than .05). In conclusion, lack of stimulation of PGI2 in the hypovolemic model suggests that PGI2 does not play a role in AC. Alternatively, it may play a role in preventing this disease process in septic shock. This study demonstrates the use of precursors of arachidonic acid and the cyclooxygenase pathway as active participants in the production of PGI2, although it is unclear whether the prostacyclin produced helps prevent AC in septic shock.
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PMID:L-alpha-phosphatidylcholine-induced stimulation of PGI2 production in canine gallbladders following hypovolemic shock and Escherichia coli sepsis. 192 May 4

The role of various chemical mediators in the development of complications after major surgery was investigated. Phospholipase A2 activity (PLA2), and the levels of pancreatic secretory trypsin inhibitor (PSTI), polymorphonuclear leukocyte elastase (PMNE), thromboxane B2 (TxB2), 6-keto-PGF1 alpha (6-KF), leukotriene (LT) B4, C4, D4, interleukin-beta (IL-1 beta), tumor necrosis factor (TNF), and endotoxin (Et) in the serum were measured in 134 surgical patients of whom 36 developed postoperative complications. PLA2, arterial TxB2 and 6-KF showed significant changes in the patients with post-operative complications, associated with elevated Et levels. The majority of these patients had a significantly higher ratio of TxB2/6-KF. These results suggest TxB2 and 6-KF, and the TxB2/6-KF ratio are useful indices of outcome in critically ill patients with hepatic failure. Our findings revealed marked production of prostanoids in sepsis and indicate a severity of the complication in balance of the thromboxane/prostacyclin axis. It was also suggested that the opsonin and eicosanoid levels are closely related to the serum endotoxin level. LTB4, C4 and D4 were increased in the patients with postoperative sepsis or DIC, especially at the initial onsets. The increased levels of IL-1 beta or TNF were observed in some patients with postoperative complications, especially those with severe postoperative complications.
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PMID:[The relationship between opsonin, endotoxin and chemical mediators in postoperative complications after surgery]. 194 9

Arachidonic acid metabolites, especially thromboxane-A2 and prostacyclin, have been shown to be increased in experimental models of sepsis and the adult respiratory distress syndrome (ARDS) and play a major pathophysiologic role. This study was designed to determine if these metabolites are increased in human sepsis syndrome and if inhibition of fatty acid cyclooxygenase affects their formation and their pathophysiologic sequelae. We conducted a double-blind, placebo-controlled trial of ibuprofen (800 mg given rectally every 4 h for three doses) in 30 patients with sepsis syndrome defined by abnormal vital signs, the appearance of serious infection, and at least one major organ failure. Urinary concentrations of the metabolite of thromboxane-A2, 2,3-dinor-TxB2, and prostacyclin, 2,3-dinor-6-keto-prostaglandin F2 alpha, were elevated 10 to 20 times normal and declined to four to five times normal by 12 h after entry in the ibuprofen-treated group and remained elevated in the placebo-treated patients. The urinary concentration of TxB2 and 6-keto-prostaglandin F1 alpha, which reflect renal production of TxA2 and prostacyclin, respectively, were also increased approximately 10-fold over normal and were subsequently decreased by ibuprofen. Coincident with the reduction in metabolite levels, the ibuprofen-treated group, but not the placebo-treated group, experienced a significant decline in temperature, heart rate, and peak airway pressure, and a trend towards more rapid reversal of shock (p = 0.12).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome. Effects of cyclooxygenase inhibition. 195 38

Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiologic features in human newborns and neonatal animal models of sepsis. Previous reports suggest that mediators in addition to TxA2 and PGI2 contribute to the late effects of GBS infusion (2 to 4 h), which include persistent increases in Ppa, hypoxemia, systemic hypotension, and a progressive fall in CO. Tumor necrosis factor (TNF) infusion in animals produces several of the late GBS effects. We hypothesized that GBS causes increased serum TNF levels 2 to 4 h into infusion in neonatal piglets. We also postulated that the TNF inhibitor, pentoxifylline (PTF), would attenuate both GBS-induced TNF production and late GBS effects. In piglets infused with 1.25 x 10(9) cfu/kg/h of GBS, serum TNF levels (pg/ml, ELISA assay) significantly increased at 2 h (231 +/- 41) and at 4 h (1,047 +/- 290, n = 9). In piglets infused with concomitant GBS + PTF, serum TNF levels at 4 h (208 +/- 39, n = 8) were reduced compared to GBS alone piglets (p less than 0.02). Control piglets infused with 0.9% saline or PTF alone for 4 h had no detectable serum TNF (less than 35). GBS alone and GBS + PTF infusion caused similar increases in serum TxB2 levels at 1, 2, and 4 h. Serum 6-keto-PGF1 alpha levels (pg/0.1 ml) significantly increased at 4 h (85 +/- 18) with GBS alone, and were more elevated at 4 h (306 +/- 75) with GBS + PTF infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Group B streptococcus induces tumor necrosis factor in neonatal piglets. Effect of the tumor necrosis factor inhibitor pentoxifylline on hemodynamics and gas exchange. 200 Oct 73


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