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

15 out of 68 patients with severe sepsis were examined in an early stage of shock and analyzed for objective hemodynamic and functional shock criteria. These data were correlated to endogenous plasma concentrations of the vasoactive arachidonate derivatives: prostaglandin F2 alpha (PGF2 alpha), thromboxane A2 (TXA2) and prostacyclin (PGI2). Marked differences in invasively measured data of cardiac, pulmonary and renal functions divided clinically otherwise comparable patients into group I and II. Group I was characterized by a hypodynamic response as compared to group II which was hyperdynamic. In spite of similar levels of PGF2 alpha (570 +/- 80 vs. 560 +/- 103 pg/ml) in both groups indicating a comparable state of arachidonate turnover, opposing profiles with regard to the TXA2/PGI2 ratio as measured from their stable degradation products were found (TXB2 [I]: a 740 +/- 184; TXB2 [II]: 280 +/- 75; 6-k-PGF1 alpha [I]: 260 +/- 117; 6-k-PGF1 alpha [II]: 940 +/- 190 pg/ml). It is concluded that early sepsis in man leads to variable profiles of endogenously released prostaglandins and thromboxane in which the predominance of PGI2 over TXA2 is associated with better cardiovascular performance and organ functions, and vice versa.
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PMID:Profiles of endogenous prostaglandin F2 alpha, thromboxane A2 and prostacyclin with regard to cardiovascular and organ functions in early septic shock in man. 354 46

An evaluation was made of 106 surgical patients with Gram-negative septic shock, both for clinical criteria as well as the biochemical mediators endotoxin, prostaglandin F2 alpha, prostaglandin I2 (prostacyclin), and thromboxane. These data were correlated to various defined shock phases, functional data of vital organs, and clinical outcome. Patients underwent invasive organ function monitoring and the usual laboratory tests of intensive care. Prostaglandins and thromboxane were measured radioimmunologically, endotoxin by the limulus amebocyte lysate test. Endotoxin proved to be a more accurate predictor of severe sepsis than did positive blood cultures. Endotoxin as well as prostaglandins and thromboxane are predominantly released in early shock phases, appearing in plasma concentrations, which correlate with the severity of organ failure. Sepsis-induced respiratory failure coincides with a deterioration of pulmonary prostaglandin inactivation, which contributes to the release mechanism. High systemic prostacyclin activity benefits the patients' organ functions and clinical outcomes, while a predominance of thromboxane seems to effect the opposite. Transpulmonary-thromboxane gradients correlate significantly with pulmonary hypertension in the early phases of septic shock.
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PMID:The clinical significance of prostaglandins and thromboxane as mediators of septic shock. 355 Feb 66

Acute, overwhelming sepsis or endotoxemia in experimental animals is associated with increased circulating levels of thromboxane (Tx)B2 (stable metabolite of TxA2) and 6-keto PGF1 alpha (stable metabolite of prostacyclin). The purpose of the present investigation was to determine the plasma prostanoid response to sepsis using an animal paradigm in which the septic process evolved more slowly than in previous similar studies. Bacterial peritonitis was induced in rats by cecal ligation (group B) or cecal ligation plus puncture with a 22-gauge needle (group C). Compared to sham-operated controls (group A), levels of immunoreactive 6-keto PGF1 alpha were significantly (p less than .05) elevated in group C rats at 6, 12, and 24 hr after surgery. At 48 hr after surgery, levels of this prostanoid were significantly (p less than .05) elevated in group B animals. In contrast, TxB2 levels were never significantly increased in septic (groups B and C) as compared to control (group A) rats. These data are consistent with results from several clinical studies and emphasize an important difference between the cecal ligation model and other experimental sepsis paradigms.
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PMID:Plasma levels of 6-keto PGF1 alpha but not TxB2 increase in rats with peritonitis due to cecal ligation. 384 Apr 15

Our purpose was to determine whether peripheral soft tissues produce and release prostanoids in response to local sepsis, and whether this mediator release can produce pulmonary dysfunction. Escherichia coli endotoxin (2 micrograms/kg in 100 mL of saline) was injected below the hide of the flank in seven unanesthetized sheep. In three additional sheep, ibuprofen (12.5 mg/kg of body weight) was injected with the endotoxin. Thromboxane B2 and 6-keto-PGF1 alpha (prostacyclin) levels were measured in tissue lymph draining the flank, lung lymph, pulmonary artery (Ppa), and aortic plasma. One hour after endotoxin administration, mean PaO2 decreased from 90 to 74 mm Hg and Ppa increased from 22 to 35 mm Hg. Lung lymph flow (QL) increased only 50% with QL being protein poor. No increase in lung or peripheral soft-tissue vascular permeability was noted. Tissue lymph (TxB2) increased from 220 +/- 114 to greater than 10,000 pg/mL with levels in Ppa plasma increasing from 300 +/- 128 to 595 +/- 124 pg/mL and aortic plasma from 270 +/- 141 to 410 +/- 104 pg/mL. Lung lymph TxB2 paralleled aortic values. Peak levels of 6-keto-PGF1 alpha in systemic lymph exceeded 2,000 pg/mL while levels in lung lymph remained relatively constant. The pulmonary injury and the increase in TxB2 was prevented by ibuprofen. We conclude that the response of soft tissue to local endotoxin is to release thromboxane in quantities sufficient to raise plasma levels and to produce hypoxia and pulmonary hypertension. The lung dysfunction is not produced by an increase in lung water or vascular permeability.
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PMID:Pulmonary dysfunction secondary to soft-tissue endotoxin. 388 49

High cardiac output sepsis is a major clinical problem. We have designed a sheep endotoxin model to simulate this condition and have evaluated how closely it approximates the clinical situation. The animals were prepared for chronic study by the implantation of cardiopulmonary catheters. One week later, endotoxin (0.75 microgram/kg/30 min) was administered following baseline measurements, and the animals were studied for an additional 15 hr. From 6-15 hr after the administration of endotoxin, there was a statistically significant twofold increase in cardiac output. Simultaneously, the total peripheral vascular resistance and mean arterial pressure was reduced. Eicosanoid measurements made at this time indicated that the vasodilator prostanoid, prostacyclin, was not elevated. A high cardiac output (hyperdynamic) model of sepsis has thus been established by the 30 min infusion of a small quantity of endotoxin. Prostacyclin is not a mediator of this response.
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PMID:A model of ovine endotoxemia characterized by an increased cardiac output. 390 75

Manipulation of prostaglandins (PG) in animal models of sepsis and acute respiratory failure (ARF) is promising. Prostacyclin (PGI2), a short-acting vasodilator, was evaluated in a porcine model of ARF produced by continuous infusion of live Pseudomonas aeruginosa (Ps.). Cardiopulmonary parameters were monitored in three groups of spontaneously breathing animals that received 0.1 micrograms PGI2/kg/min begun 20 min after baseline (Group I); 2 X 10(8) Ps./20 kg/min (Group II); identical Ps. infusion and then PGI2 begun at 20 min (Group III). The decrease in mean arterial blood pressure and cardiac index with Ps. infusion was improved by PGI2 treatment. In Groups II and III, mean pulmonary artery pressure (PAP) doubled (P less than 0.005) and pulmonary vascular resistance (PVR) tripled (P less than 0.01) by 15 min. Both PAP and PVR were decreased significantly with PGI2 treatment. In both Ps. groups, significant hypoxemia occurred. PGI2 improves cardiac output and acts as a pulmonary vasodilator, but does not improve oxygenation in this porcine model of severe ARF.
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PMID:Prostacyclin in experimental septic acute respiratory failure. 633 18

Prostacyclin, or prostaglandin I2 (PGI2), and thromboxane A2 (TXA2) are potent, endogenously produced, vasoactive substances that have been implicated as mediators in the pathophysiologic nature of septic shock. We investigated the contribution and production of PGI2 and TXA2 in sepsis and septic shock, using an intact rabbit model and an in vitro rabbit isolated cardiac perfusion model. Continuous hemodynamic monitoring of both experimental models, along with serial radioimmunoassays of the metabolites of PGI2 and TXA2, indicated that myocardial depression is a common finding in subjects with septic shock and that septic shock causes a suppression of PGI2 production while augmenting TXA2 production. In addition, PGI2 and TXA2 were mediators of some cardiovascular changes in septic shock but were themselves not the toxic factor(s) responsible for the associated myocardial depression.
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PMID:The role of prostacyclin and thromboxane in sepsis and septic shock. 636 31

Seventeen piglets were infected with a continuous intravenous infusion of live group B beta-hemolytic streptococci (GBS). Hemodynamic changes were recorded, and blood samples were drawn for measurement of thromboxane B2 (TxB2) (stable metabolite of thromboxane A2) and 6-keto-PGF1 alpha (stable metabolite of prostacyclin). Control animals (n = 9) received only bacteria, while treatment animals (n = 8) received indomethacin, 3 mg/kg IV, 15 min after the start of the bacterial infusion. Control animals responded to the bacteria within 15 min with marked elevation in mean pulmonary artery pressure (Ppa) from 15 +/- 8 to 39 +/- 6 mm Hg and decline in PaO2 from 80 +/- 11 to 51 +/- 6 mm Hg and cardiac output (CO) from 0.24 +/- 0.07 to 0.13 +/- 0.07 liters/min/kg. Mean arterial blood pressure (AoP) significantly decreased from baseline value of 95 +/- 13 to 51 +/- 32 mm Hg by 180 min. In animals treated with indomethacin, these changes were reversed or significantly attenuated. The hemodynamic changes were associated temporally with elevations in plasma concentrations of TxB2 or 6-keto-PGF1 alpha. In the first 60 min, TxB2 levels in both groups correlated with Ppa (r = 0.72, p less than 0.001) and PaO2 (r = -0.60, p less than 0.001). A strong negative correlation between TxB2 and CO was observed over the first 180 min (r = -0.73, p less than 0.001). There was a statistically significant correlation between AoP and 6-keto-PGF1 alpha concentration between 60 and 180 min (r = -0.54, p less than 0.002). Indomethacin improved the hemodynamic function in this model of GBS sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular changes in group B streptococcal sepsis in the piglet: response to indomethacin and relationship to prostacyclin and thromboxane A2. 638 9

Levels of both thromboxane B2 and 6-keto-prostaglandin-F1a, the stable metabolites of thromboxane A2 and prostacyclin, respectively, were quantitated in plasma samples from burn patients at various times postinjury. Our results indicate that, although thromboxane B2 levels were elevated throughout the burn course, quite large increases occurred both in the acute stage (less than three days postinjury) and during septic episodes. The results of our study demonstrate that, at the same time thromboxane B2 levels were elevated, 6-keto-prostaglandin-F1a levels were unchanged and remained at control levels. Increased production of thromboxane B2 without a concomitant increase in 6-keto-prostaglandin-F1a in the plasma of burn patients gives support to the hypothesis that elevated thromboxane A2 production contributes to post-thermal injury systemic responses, both in the acute phase as well as during sepsis.
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PMID:Increased thromboxane B2 levels in the plasma of burned and septic burned patients. 643 94

The potential role of thromboxane (TxA2), a platelet aggregator and vasoconstrictor, and prostacyclin (PGI2) a platelet anti-aggregator and vasodilator, in endotoxic and septic shock was investigated. Early endotoxic shock in the rat is associated with marked elevations of plasma TxB2 (the stable metabolite of TxA2) and lesser increases in plasma 6-keto-PGF1 alpha (the stable metabolite of PGI2). Selective inhibition of TxA2 synthesis by several different chemical classes of Tx synthetase inhibitors was beneficial in endotoxic shock. In contrast, shock induced by acute intra-abdominal sepsis in the rat was characterized by high levels of plasma 6-keto-PGF1 alpha, which exceeded plasma TxA2 six- to eight fold at most time intervals studied. Tx synthetase inhibitors were not protective in this model of acute sepsis, but treatment with fatty acid cyclo-oxygenase inhibitors, an antibiotic (gentamicin), or reduction in arachidonic acid metabolism by essential fatty acid (EFA) deficiency significantly prolonged survival time. An important aspect of the latter study is that decreased arachidonic acid metabolism was an effective adjunct to antibiotic therapy. Conjoint administration of gentamicin in EFA-deficient rats or with indomethacin synergistically improved long-term survival, a result that was not evident with single treatment interventions. In addition to experimental studies, plasma TxB2 levels were measured during clinical sepsis. These studies demonstrated that plasma TxB2 levels were elevated tenfold in patients dying of septic shock compared with septic survivors or nonseptic controls. These composite experimental and clinical observations suggest that arachidonic acid metabolites play a role in the pathogenesis of endotoxic and septic shock.
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PMID:The potential role of thromboxane and prostacyclin in endotoxic and septic shock. 644 May 69


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