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

Inadequate tissue oxygenation may occur in critically ill patients with sepsis despite an apparently adequate O2 transport (QO2), and this may contribute to the development of an O2 debt and also to multiple organ failure. It has been shown that increasing QO2 by infusing a vasodilator may reveal this O2 debt in septic patients. To investigate whether the site of action of vasodilators may be of importance in unmasking such an O2 debt, we administered prostacyclin, a prostaglandin with a preferential effect on the microcirculation, and phentolamine, an arteriolar vasodilator, in 11 patients studied during the first 48 hours after the onset of sepsis, and compared their effect on whole body oxygen consumption (VO2) and skin microvascular blood flow. The results demonstrated that increasing QO2 by prostacyclin but not by phentolamine significantly increases VO2 in critically ill patients with sepsis. The site of action of vasodilators may therefore play an important role in their ability to unmask an O2 debt.
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PMID:Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. 224 90

Persistent pulmonary hypertension of the newborn (PPHN), initially described by Gersony et al as persistent foetal circulation (PFC syndrome), results from a flawed transition from foetal to extrauterine pulmonary circulation. It is characterised by the maintenance of a high pulmonary vascular resistance and right-to-left shunting through the ductus arteriosus and foramen ovale. Infants with a wide variety of underlying clinical conditions develop PPHN. According to Rudolph three main anatomic types of PPHN can be identified: normal pulmonary vascular development increased pulmonary vascular smooth muscle development decreased cross-sectional area of pulmonary vascular bed. It is important to realize that several pathophysiologic mechanisms may coexist and interact. Besides metabolic and respiratory acidosis, hypercapnia and hypoxaemia some other factors induce pulmonary vasoconstriction. Thromboxane, leukotrienes and prostaglandins play a decisive role. Since PPHN can be associated with a broad spectrum of clinical conditions, a specific clinical picture is lacking. The baby is usually term or post-term, cyanotic immediately after birth or some hours later. Birth asphyxia, hyperviscosity, sepsis and aspiration of meconium have been recognized as predisposing factors. The diagnosis can be confirmed by echocardiography. Contrast echo will indicate right-to-left shunting with normal anatomy. Currently hyperventilation, tolazolin, chlorpromazin and dopamine/dobutamine have been advocated as central foci for clinical therapy. Recently prostacyclin was introduced as a specific pulmonary vasodilatator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Persistent pulmonary hypertension of newborn. The PFC syndrome]. 229 36

Ibuprofen is a potent cyclooxygenase inhibitor known to reduce the production of arachidonic acid metabolites. Prostacyclin and thromboxane are well-studied metabolites that play a prominent role in inflammation. Many of the effects of ibuprofen can be linked to its anti-inflammatory properties. Beneficial results from ibuprofen therapy have been documented, and more widespread use of the drug seems indicated. Conditions ranging from immunologic response to trauma and sepsis to postburn lung dysfunction to wound edema are improved by the use of ibuprofen. The fact that ibuprofen is effective in the various conditions detailed above, while other steroidal and nonsteroidal drugs are effective only in selective instances, increases the value of ibuprofen. Other properties of the drug, aside from its anti-inflammatory effects, are not as well studied and not as well known. Their importance, however, should not be overlooked. Superoxide radical tissue injury may be very important in acute injury and this phenomenon needs further study. In several studies ibuprofen has been shown to antagonize this type of injury. Similarly fibrinolysis inhibition is known to occur in burn wounds, but its role in other injuries is unknown. The antagonism of this inhibitor by ibuprofen maintains vascular patency. The clinical use of ibuprofen will increase as research further elucidates the mechanisms of tissue injury in acute situations and the many and varied mechanisms of action of ibuprofen.
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PMID:Ibuprofen in acute-care therapy. 240 73

Septic shock was induced by intravenous infusion of live Escherichia coli in pigs to investigate the influences on central hemodynamic, coagulation, and fibrinolytic reactions by a thromboxane A2 (TxA2)-receptor blocker (BM 13.177; n = 6) and a prostacyclin analogue (iloprost or ZK 36,374; n = 7). The early pulmonary vasoconstriction following E coli infusion was attenuated, but not abolished, by BM 13.177. Only minor effects were seen after pretreatment with iloprost. Neither drug had any major effect on the coagulation and fibrinolytic activation. These results confirm that TxA2 is an important, but not the only, mediator of early pulmonary vascular response in porcine septicemia and that neither TxA2 nor prostacyclin is of major importance for the hemostatic reactions in this shock model.
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PMID:Thromboxane A2-receptor blockade and prostacyclin in porcine Escherichia coli shock. 247 90

The role of the various cyclo-oxygenase products of arachidonic acid metabolism in the production of the pathologic, physiologic, hemodynamic, and metabolic derangements of sepsis has been reviewed and there is a wide variation in different species and with different models of sepsis. The relationship of these potential mediators cannot be definitely determined. There is much circumstantial evidence that would incriminate the various arachidonic metabolites in the production of the sepsis manifestations; however, we must keep in mind that this may only be "guilt by association." Clearly, the available evidence does suggest that there is some role played by TXA2 and PGI2 in the physiologic and hemodynamic manifestations of sepsis, but the exact role remains undetermined.
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PMID:Prostaglandins, cyclo-oxygenase inhibitors, and thromboxane synthetase inhibitors in the pathogenesis of multiple systems organ failure. 249 47

Escherichia coli hemolysin has been implicated as a pathogenicity factor in extraintestinal E. coli infections including sepsis. In the present study the effects of intravascular administration of hemolysin were investigated in isolated blood-free perfused rabbit lungs. Low concentrations of the toxin in the perfusate (0.05-5 hemolytic units/ml, corresponding to approximately 5-500 ng/ml), caused a dose- and time-dependent release of potassium, thromboxane A2, and prostaglandin I2, but not of lactate dehydrogenase, into the recirculating medium, as well as a dose-dependent liberation of the prostanoids into the bronchoalveolar space. These events were paralleled by a dose-dependent pulmonary hypertension, and studies with different inhibitors collectively indicated that the vasoconstrictor response was mediated predominantly by pulmonary thromboxane generation. In addition, E. coli hemolysin elicited a protracted, dose-dependent increase in the lung capillary filtration coefficient, which was independent of the prostanoid-mediated pressor response and resulted in severe pulmonary edema formation. We conclude that E. coli hemolysin can elicit thromboxane-mediated pulmonary hypertension combined with severe vascular leakage in isolated lungs in the absence of circulating inflammatory cells and humoral mediator systems, mimicking the key events in the development of acute respiratory failure in states of septicemia.
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PMID:Thromboxane-mediated hypertension and vascular leakage evoked by low doses of Escherichia coli hemolysin in rabbit lungs. 250 Apr 55

Thirty multiply injured blunt-trauma patients at high risk for development of ARDS (multisystem trauma including more than one organ or extremity, Injury Severity Score of 26 or more, hypotension and need for 1500 mL or more blood within the first hour after admission, and PaO2 less than or equal to 70 torr) were studied sequentially with blood and physiologic evaluations beginning immediately after injury and every eight hours for eight days, or until death, to study the evolution of the ARDS process. Mixed venous blood samples were obtained for eicosanoids PGE2, PGF2 alpha, thromboxane B2, PGI2 (6-KetoPGF1 alpha) and leukotriene B4 (LTB4). Platelet (PLAT), and neutrophil (WBC) counts were also done and plasma elastase was measured. At 7:00 AM each day patient neutrophils were obtained for a study of zymosan-activated superoxide production using a chemiluminescence assay. These data were correlated with physiologic measurements of the Respiratory Index (RI), per cent pulmonary shunt (QS/QT), and respiratory compliance measures. Seven patients developed a fulminant post-traumatic ARDS syndrome within 96 hours after injury. Twelve patients without ARDS developed sepsis (TS) four or more days after injury, and 11 had uncomplicated postinjury courses (TR). Compared to both TR and TS, ARDS had a significant (p less than 0.01) rise in neutrophil superoxide production beginning on day 2 through day 4 after injury. This was preceded by rises in PGE2 and LTB4, which were significantly correlated with subsequent falls in PLAT and WBC and rises in TXB2, PGF1, and superoxide production and followed by increases in RI, QS/QT, and a fall in compliance. The significant difference in the pattern and sequence of events in ARDS compared to TR and TS patients suggests that in ARDS the earliest event may be related to peripheral release of PGE2 and LTB4 due to platelet activation and lung sequestration with release of PGF2 alpha, and by aggregation and leukocyte adherence with release of elastase. However, fulminant ARDS mortality appears to be related to the subsequent amplification of the LTB4 leukocyte activation with superoxide production that does not achieve significance before the second day after injury and rises to a maximum by day 4 after injury. These data suggest that post-trauma ARDS follows a different evolutionary pattern than that reported in animal models and is also different from that seen in human TS or TR patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sequential patterns of eicosanoid, platelet, and neutrophil interactions in the evolution of the fulminant post-traumatic adult respiratory distress syndrome. 254 91

Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.
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PMID:Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat. 267 Jul 94

The complex role of adrenergic mechanisms in the pathogenesis of sepsis and shock remains incompletely understood. Recent reports have suggested that adrenergic mechanisms may play an important modulatory role in arachidonate metabolism during early sepsis, specifically in the synthesis of the vasoactive metabolites thromboxane A2 and prostacyclin. The purpose of the present set of experiments was to evaluate the extent to which adrenergic mechanisms contribute to early alterations in regional perfusion during Gram-negative bacteremia, using the mixed alpha adrenergic receptor antagonist phenoxybenzamine hydrochloride. Male Sprague-Dawley rats received a 3-hour continuous intraarterial infusion of either saline (n = 7) or 6.6 +/- 0.4 x 10(8) live E. coli colony forming units (n = 7), after which regional perfusion was determined using 51Cr-labelled microspheres (16.5 +/- 0.1 micron). Significant reductions (p less than 0.05) in blood flows to the renal, gastric, cecal, pancreatic, and splenic beds, as well as a reduction (p less than 0.05) in the calculated portal venous flow, were observed in the bacteremic group while mean arterial blood pressure remained unchanged. Further experiments conducted in 14 rats with preexisting alpha adrenergic receptor blockade revealed relative preservation of renal, gastric, cecal, and portal venous blood flows during bacteremia. These data identify alterations in regional perfusion during early E. coli bacteremia occurring before changes in systemic arterial blood pressure, and indicate that adrenergic mechanisms participate in the modulation of such.
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PMID:Adrenergic mechanisms contribute to alterations in regional perfusion during normotensive E. coli bacteremia. 267 1

Endogenous formation of thromboxane A2 and prostacyclin were evaluated in seven neonatates with persistent pulmonary hypertension by serial gas chromatographic mass spectrometric determination of their urinary metabolites dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha, respectively. The patients were studied until their hypertension had resolved on clinical criteria. Urinary excretion of dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha was increased when the persistent pulmonary hypertension was associated with group B streptococcal (n = 2) and pneumococcal (n = 1) sepsis. Based on urinary metabolite excretion, endogenous formation of thromboxane A2 and prostacyclin did not consistently differ from normal neonates in four patients with non-septic persistent pulmonary hypertension (hyaline membrane disease (n = 2), asphyxia, and meconium aspiration). These data suggest that thromboxane A2 is not a universal mediator of persistent pulmonary hypertension. It may, however, have a role in the pathophysiology of early onset group B streptococcal disease, and persistent pulmonary hypertension of other infectious aetiology. If these findings are confirmed by further studies, thromboxane synthetase inhibition or receptor antagonism may offer a potential therapeutic approach in neonates with persistent pulmonary hypertension associated with sepsis.
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PMID:Endogenous formation of prostanoids in neonates with persistent pulmonary hypertension. 267 60


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