thromboxane-b2 and Multiple-Organ-Failure

The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor alpha (TNF-alpha and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis.. The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada.. Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection.. Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle).. Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-alpha and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients).. Hypothermic sepsis has an incidence of approximately 10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-alpha and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Epoprostenol; Female; Fever; Humans; Hypothermia; Ibuprofen; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Sepsis; Survival Analysis; Thromboxane B2; Time Factors; Tumor Necrosis Factor-alpha

Acute organophosphorus pesticides poisoning has a serious threat on people's health. This study aimed to investigate the pathogenesis and molecular mechanism of multiple organ dysfunction syndrome (MODS) in severely monocrotophos-poisoned rabbits.. Chinchilla rabbits were used to build the monocrotophos-poisoned animal model via subcutaneous abdominal injection. Acetylcholinesterase activity was determined using the dithiobisnitrobenzoic acid enzyme kinetics method, and the free organophosphorus (FOP) toxic substances content was analyzed using the enzyme inhibition method. The contents of tumor necrosis factor (TNF-α), interleukin 1-β (IL-β) and thromboxane B. Twenty-four hours after exposure, in comparison to the plasma, blood cells and homogenates of various tissues, the bile had a significantly different FOP content (P < 0.05). In different phases, HE staining results confirmed that several degrees of pathological lesions (such as hemorrhage, edema, degeneration and necrosis) were detected in FOP poisoned rabbits. The TXB. FOP stored in the gallbladder may play important role in enterohepatic circulation. In MODS rabbits, caused by OP poisoning, the TXB

Topics: Acetylcholinesterase; Animals; Insecticides; Interleukin-1beta; Kidney; Liver; Monocrotophos; Multiple Organ Failure; Rabbits; Radioimmunoassay; Thromboxane B2; Tumor Necrosis Factor-alpha

In this study the authors assessed the sequential release of lipid mediators (TXB2, PGE2, 6-keto-PGF1alpha, LTB4, LTC4, PAF), pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-10) in 17 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Time course of appearance of inflammatory mediators revealed the early and transient increase in lipid mediator plasma concentrations (6-keto-PGF1alpha, LTB4, LTC4, PAF) whereas cytokines (IL-6, IL-8, IL-10) were involved only in late pre- and post-operative periods. No variation of TXB2, PGE2, IL-4 and TNF-alpha levels were found. No correlation was documented between the levels of lipid mediators and pro- or anti-inflammatory cytokines suggesting that lipidic compounds are not implicated in the genesis of cytokines which appear much later involved. Despite the common use of high doses of aprotinin (a non-specific enzyme inhibitor) in hope to abrogate the inflammatory response to cardiopulmonary bypass procedure, this study reports the persistent release of several inflammatory compounds that might be involved in the post-CABG multiple organ failure syndromes.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents; Cardiopulmonary Bypass; Cytokines; Dinoprostone; Extracorporeal Circulation; Humans; Inflammation Mediators; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Leukotriene B4; Leukotriene C4; Lipid Metabolism; Lipids; Multiple Organ Failure; Platelet Activating Factor; Prospective Studies; Thromboxane B2; Tumor Necrosis Factor-alpha

These serial clinical and experimental studies were designed to clarify the pathogenesis of postburn MODS. Both animal and clinical studies were performed. In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were used as controls). The burned dogs were randomly divided into 4 groups: immediate infusion, delayed infusion, delayed fast infusion and delayed fast infusion combined with ginsenosides. All dogs were kept under constant barbiturate sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase (SDH), organ water content as well as light and electron microscopy of visceral tissues were determined. In the clinical study, 61 patients with extensive deep burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2, interleukin-1, total organ water content and pathological observations of visceral tissues from patients who died of MODS were carried out. Results demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and inhalation injury are three main causes of postburn death. All inflammatory mediators increased markedly in both animals and patients who sustained organ damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings suggested that ischemic damage and systemic inflammatory response syndrome (SIRS) initiated by mediators or cytokines might be important in the pathogenesis of postburn MODS.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Adenosine Triphosphate; Adult; Animals; Body Water; Burns; Central Nervous System Agents; Dinoprostone; Dogs; Female; Fluid Therapy; Ginsenosides; Hemodynamics; Humans; Hypnotics and Sedatives; Interleukin-1; Male; Malondialdehyde; Mitochondria; Multiple Organ Failure; Oxygen Consumption; Panax; Plants, Medicinal; Platelet Aggregation; Random Allocation; Reperfusion Injury; Saponins; Sepsis; Shock; Succinate Dehydrogenase; Superoxide Dismutase; Syndrome; Systemic Inflammatory Response Syndrome; Thromboxane B2; Tumor Necrosis Factor-alpha

To evaluate the posttraumatic course of several inflammatory mediators or markers (complement components C3, C3a, terminal complement complex, thromboxane B2, C-reactive protein, elastase, and neopterin) in relation to the development of multiple organ failure and mortality.. Prospective study of a selected patient group.. Surgical intensive care units in three European trauma hospitals.. Patients (n = 56) with severe blunt trauma (Injury Severity Score of > or = 33).. Arterial blood samples were sequentially obtained.. Nonsurvivors (n = 8) had significantly higher circulating C3a and elastase concentrations on the first postinjury day, compared with survivors (n = 48). No differences between these groups were found for terminal complement complex, thromboxane B2, C-reactive protein, and the neopterin/creatinine ratio. Five patients died before day 5. Eighteen patients developed multiple organ failure, which was diagnosed from day 5 onward, leaving 33 patients without multiple organ failure. The patients with subsequent multiple organ failure showed significantly higher mean circulating concentrations of C3a (914 +/- 190 [SEM] ng/mL), terminal complement complex (57 +/- 17 U/mL), and thromboxane B2 (275 +/- 37 pg/mL) at the first postinjury day than the patients without multiple organ failure (566 +/- 110 ng/mL, 27 +/- 2 U/mL, and 169 +/- 14 pg/mL, respectively). In patients with multiple organ failure, elastase concentrations were significantly higher on days 2, 3, 4, and 5 postinjury. Neopterin/creatinine ratios, on the other hand, were significantly higher in patients with multiple organ failure when the multiple organ failure had already become established (on days 8 and 10).. In multiple trauma patients, excessive triggering of the inflammatory cascade-as expressed by complement activation and stimulation of neutrophils producing elastase--plays an important and early role in the development of multiple organ failure.

Topics: Adolescent; Adult; Aged; Biopterins; C-Reactive Protein; Complement C3; Complement C3a; Complement Membrane Attack Complex; Female; Humans; Inflammation Mediators; Injury Severity Score; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Neopterin; Pancreatic Elastase; Prospective Studies; Thromboxane B2; Wounds, Nonpenetrating

To define the pathogenesis of hemodynamical and hemorrheological changes as well as multiple organ failure (MOF) during early postburn stage, we determined the levels of thromboxane A2(TXA2) and prostacyclin (PGI2) and some other related variables in 57 patients, of which 14 were complicated by MOF. The results showed that TXA2/PGI2 ratio increased markedly within 3 days postburn, and its dynamic change paralleled well with changes of hemodynamical and hemorrheological parameters as well as myocardial enzyme spectrum. Both plasma and visceral levels of TXA2/PGI2 ratio were significantly higher in MOF than those in non-MOF cases. The altered TXA2/PGI2 ratio coincided with the clinical course of MOF patients. These findings suggested that TXA2/PGI2 imbalance may be one of the important factors of early postburn damage.

Topics: 6-Ketoprostaglandin F1 alpha; Burns; Female; Humans; Male; Multiple Organ Failure; Thromboxane B2

A prospective study was carried out on 57 patients with total burned surface area (TBSA) over 30%. It was found that myocardial damage occurred early postburn, which was one of the major causes of cardiac dysfunction and failure. The postburn respiratory failure (RF) might be classified into three patterns. The etiology of each pattern varied. The imbalance between thromboxane and prostacyclin in plasma and visceral tissues played important roles in the genesis and development of postburn MOF as well as the causes of pathophysiological alterations in the main factors (including inhalation injury, severe shock and systemic infection) which contributed to occurrence of visceral damage and MOF.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Burns, Inhalation; Child; Female; Humans; Male; Multiple Organ Failure; Prospective Studies; Shock, Traumatic; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Dinoprost; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Thromboxane B2

51 burned patients with TBSA over 30% were studied prospectively. MOF developed in 17 of them. Postburn MOF occurred mainly in those with TBSA over 70%. Mortality of MOF was directly proportional to the number of organs involved. The incidence of pulmonary failure was the highest, and the highest mortality was attributed to renal failure. MOF occurring in the early stage was more related to burn shock, and those occurring in the late stage was predisposed mainly by infection. Oxygen free radicals play an important role in the genesis and development of postburn MOF. In this study, it was revealed that antiperoxidation ability declined, active oxygen was increased, and lipid peroxidation became excessive after the burn injury. It was also found that oxygen free radical-mediated effects produced more serious damages in patients with MOF than those without, and also more in those died than the survivors. The hypoxanthine-xanthine oxidase system was a significant source of oxygen radicals after the burn injury. There were also significant changes in plasma TXA2 and PGI2 levels postburn. The marked increase in TXA2/PGI2 ratio indicated imbalance between TXA2 and PGI2, which was correlated well with burn size and closely related to the development of postburn MOF. The excessive production of TXA2 might trigger or accelerate the formation of microaggregates and thromboxane, subsequently leading to visceral damages and failure.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Burns; Female; Humans; Male; Malondialdehyde; Multiple Organ Failure; Shock, Traumatic; Superoxide Dismutase; Thromboxane B2; Xanthine Oxidase

Forty dogs were divided randomly into four groups. The portal circulation was reduced to 50%-60% for one hour by partially occluding the superior mesenteric artery (SMA) for the purpose of determining the relationship between the reperfusion injury, bacterial translocation, and multiple system organ failure. Escherichia coli 0111 B4 (1 x 10(10)/kg) was fed to each animal 12 hours before operation. Group I constituted the controls, in which a sham operation was done. The experimental procedure was completed in all the animals of the other three groups. The group-II animals received no further manipulation. Rubia yunnanensis, an antioxidant, was given to the animals in group III. Amikacin was given to the animals in group IV. The results showed that the animals in group II developed bacteremia, hypoxemia, and hypotension compared with the animals in group I. The levels of superoxide dismutase (SOD) in whole blood were markedly lowered in group-II animals, with malondialdehyde (MDA) values significantly elevated after reperfusion when compared with group I. Plasma levels of anaphylatoxin C5a and thromboxane B2 (TXB2) were significantly raised in group-II animals beginning from reperfusion when compared with the animals in group I, group III, and group IV. Pathologic changes in the intestine, liver, and lung were marked only in the group-II animals, including acute necrosis of the intestinal mucosa, granulocyte infiltration, and bacterial invasion of the liver and lung. These results suggested that bowel ischemia and reperfusion may promote gut barrier failure and bacterial translocation, then contribute to the development of MSOF by allowing bacteria or endotoxin normally contained within the gut to reach the portal and systemic circulations, where it fuels the septic process. Oxygen free radicals, anaphylatoxin, and thromboxane may be potential factors in the development of gut barrier failure and MSOF.

Topics: Animals; Bacteremia; Complement C5a; Dogs; Escherichia coli; Intestines; Ischemia; Malondialdehyde; Multiple Organ Failure; Reperfusion; Superoxide Dismutase; Thromboxane B2

We compared the time course of plasma and pulmonary lymph levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin (PG)F1 alpha during the development of either the hyperdynamic phase of sepsis or of the multiple organ failure syndrome (MOFS) associated with sepsis in 26 chronically instrumented awake sheep with intravascular catheters and a chronic pulmonary lymph fistula. Using a continuous i.v. infusion of Escherichia coli endotoxin administered at a rate of 20 ng.kg-1.min-1 (group E20, n = 9) resulted in hyperdynamic septic shock with more than 75% of animals surviving after 72 h of continuous endotoxin administration. Infusing endotoxin at a higher dosage (40 ng.kg-1.min-1; group E40, n = 9) resulted in the development of respiratory failure and MOFS with death occurring within 55 hr of endotoxemia. Eight similarly instrumented sheep served as controls. Administration of endotoxin produced within 4 hr in both endotoxin groups a significant increase in arterial plasma concentration of TxB2, which was not significantly different between both endotoxin groups. Thereafter, plasma TxB2 concentrations progressively decreased in the E20 group to reach at 36 hr values significantly lower than those measured in control sheep not given endotoxin. In the E40 group, plasma TxB2 concentrations returned to baseline values during the development of a MOFS. The time course of TxB2 concentrations in pulmonary lymph in both endotoxin groups was similar to that measured in each group in plasma. 6-Keto-PGF1 alpha concentrations in arterial plasma and pulmonary lymph were significantly higher than in controls during the first 20 hr following the start of endotoxin infusion in both endotoxin groups and were not different between these groups. Thereafter, plasma and pulmonary lymph 6-keto-PGF1 alpha concentrations progressively returned to baseline values in the E20 group and remained at these levels up to the end of the study period (72 hr). In the E40 group, plasma 6-keto-PGF1 alpha concentrations also decreased to baseline values during the second day of endotoxemia but then significantly increased in sheep that survived more than 36 hr and developed a hypodynamic septic state. During the first 24 hr of endotoxemia, the plasma TxB2/6-keto-PGF1 alpha ratio was similar in controls and in both endotoxin groups. During the second study day, TxB2/6-keto-PGF1 alpha ratio progressively decreased in both endotoxin groups to reach and maintain values significantly lower than tho

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Escherichia coli; Female; Hemodynamics; Kinetics; Lung; Lymph; Male; Multiple Organ Failure; Sheep; Shock, Septic; Thromboxane B2

Topics: Animals; Digestive System; Endothelium; Humans; Interleukin-1; Lung; Macrophages; Multiple Organ Failure; Neutrophils; Prostaglandins; Rabbits; Respiratory Distress Syndrome; Shock, Septic; Syndrome; Thromboxane B2