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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology of the shock state includes a variety of hemodynamic changes such as systemic hypotension, pulmonary hypertension and increased vascular permeability leading to the extravasation of protein rich plasma. These changes can be initiated by different etiological factors, but many of them have been related to the stimulation of activation systems (complement, kinins, etc.) or to the generation of inflammatory mediators. The purpose of the present study has been to obtain evidence of the involvement of paf-acether in the pathogenesis of the shock state initiated in rat and mouse by Gram-negative bacteria and soluble aggregates of immunoglobulin G. The injection of 1-2 MDa aggregates of immunoglobulin G to normal Sprague-Dawley rats, induced a dose-dependent systemic hypotension which appeared about five minutes after completion of the intravenous challenge. Simultaneously, extravasation of protein-rich plasma occurred as judged from the finding of an increased clearance of 125I-BSA. In similar experiments in mice, a reduction of the vascular volume was observed using 51Cr-labelled homologous red blood cells. Under these conditions, a lipid compound analogous to paf-acether was obtained from the liver and the spleen of these animals. The generation of this compound preceded the development of blood volume depletion and could be suppressed by either quinacrine or depletion of mononuclear phagocytes by total irradiation with 700 rads. The previous treatment of the rats with the compound BN 52021 (a specific antagonist of the paf-acether receptor) at a dose of 5mg/kg, i.v., prevented the appearance of hypotension and extravasation in response to an i.v. challenge with soluble aggregates of immunoglobulin G. Interestingly, the reversal of hypotension was also observed when BN 52021 was infused after the immunoaggregates (5mg/kg). The possible involvement of paf-acether in the hemodynamic changes of Gram-negative sepsis was studied in rats which had received an intraperitoneal inoculation of E. coli. The animals inoculated with the doses of bacteria which produced mortality showed a time- and dose-dependent increase of vascular permeability as judged from the presence of abundant peritoneal exudate and the reduction of the circulating volume. Simultaneously, significant amounts of paf-acether could be obtained from the peritoneal exudate and from the spleen preceding to the development of the circulating volume depletion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence of a role for PAF-acether in the pathophysiology of the shock state. 377 44

Although gram-negative sepsis is a major cause of neonatal morbidity and mortality, our understanding of endotoxemia in the neonate has been hampered by the lack of experimental models. Previous studies have suggested neonatal hyporesponsiveness to endotoxin. We studied unanesthetized neonatal lambs which had been exposed to the environment prior to study. These animals demonstrated the classic early phase changes of endotoxemia including pulmonary hypertension which was dependent upon prostanoid production. This model allows further studies of endotoxemia in the neonate.
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PMID:Endotoxemia in the neonatal lamb. 388 82

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

Myocardial performance in critically ill patients is primarily responsive to the need to supply O2 to the periphery. An increase in CO is the common finding in an acute illness characterized by an increase in systemic VO2 (for example, sepsis and trauma), since acute variations in flow are the most efficacious mode of augmenting systemic O2t to match the VO2. The lower systemic VO2 of a patient with an acute cardiac illness explains why the CO in this disease is not as elevated as that found in the acutely ill patient with sepsis or trauma. Endogenous compensatory mechanisms used to vary flow according to the need for O2t include heart rate, ventricular preload, contractility, and afterload. An increase in LV contractility and a reduction in afterload facilitate LV stroke volume, hence O2t. Conversely, pulmonary hypertension may result in a restriction of LV preload if RV pump failure ensues. Other factors relevant to the care of the critically ill that will decrease LV preload--and thus reduce the heart's left-sided adaptation to maintain O2t--include the presence of underlying cardiac disease, which will limit any necessary increase in contractility, and the use of PEEP, which will restrict venous return to the RV. Therapeutic intervention is required when O2t does not balance systemic VO2 and arterial lactate levels rise. The use of resuscitative fluid to improve flow by the Frank-Starling (preload) mechanism may be limited by the compliance properties of either ventricle, but it is a reasonable first choice, with guidelines for administration determined by the PCWP, which influences fluid flux across the pulmonary microvascular exchanging membrane. Vasodilators may be used to increase CO by reducing impedance to ventricular ejection; they may also improve LV compliance, thereby allowing the administration of more fluid (that is, increasing preload) without an untoward rise in the PCWP. If vasodilators are without effect or are potentially dangerous because of concomitant hypotension, inotropic support to increase O2t is required. A brief summary of interventional pharmacologic support in acute illness is depicted in Figure 8.
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PMID:Myocardial function in the critically ill: factors influencing left and right ventricular performance in patients with sepsis and trauma. 390 47

The effects of prophylactic and delayed treatment with high-dose methylprednisolone were evaluated in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with methylprednisolone i.v., 60 mg . kg-1, followed by an i.v. infusion at a rate of 10 mg . h-1 . kg-1. Ten animals received the same dosage of methylprednisolone beginning 2 h after the start of endotoxin infusion. Pretreatment with methylprednisolone prevented the endotoxin-induced impairment in pulmonary gas exchange and the development of pulmonary oedema. The pulmonary hypertension was counteracted. Cardiac output (Qt) and O2 delivery were improved. Mean arterial blood pressure (MAP) increased and was higher than in the untreated endotoxin group. The profound fall in PMN count was inhibited, while the accumulation of these cells in the lung was still substantial. Survival was improved. Delayed methylprednisolone treatment prevented further deterioration in pulmonary gas exchange and tended to restore it towards baseline. The pulmonary oedema and pulmonary hypertension were reduced. Qt and O2 delivery did not improve. MAP was higher than in the untreated endotoxin group towards the end of the observation period. The decline in PMN count and the pulmonary accumulation of these cells were not significantly influenced. Survival was improved. These results indicate that high-dose methylprednisolone, when given early in the course of sepsis, might be of clinical value in prevention of the devastating pulmonary and circulatory complications of this disease.
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PMID:Prophylactic and delayed treatment with high-dose methylprednisolone in a porcine model of early ARDS induced by endotoxaemia. 390 10

Levels of thromboxane B2 (TxB2), the stable metabolite of thromboxane A2, are elevated in human and experimental septic shock. The thromboxane synthetase inhibitor dazoxiben has improved survival and decreased pulmonary hypertension in experimental endotoxemia. A randomized prospective study of 10 patients with the clinical diagnosis of sepsis and early adult respiratory distress syndrome (hypoxemia, radiologic evidence of the syndrome, and intrapulmonary shunt greater than 20%) was performed to test the efficacy of dazoxiben in ameliorating the effects of human sepsis. Five subjects received dazoxiben and five received placebo. Dazoxiben, 100 mg, or placebo was injected intravenously every 4 hours for a maximum of 72 hours. Plasma immunoreactive TxB2 (iTxB2) levels were determined by radioimmunoassay. Before dazoxiben, the plasma iTxB2 level was 752 +/- 261 pg/ml (n = 5) and was reduced within 1 hour to 333 +/- 137 pg/ml. The plasma levels of iTxB2 remained significantly decreased with subsequent doses of dazoxiben and it was 201 +/- 67 pg/ml (n = 4) 60 hours after dosing. In contrast, placebo had no significant effect on plasma iTxB2 levels (n = 5) throughout the entire period of observation. Dazoxiben did not induce any significant changes in pulmonary or systemic vascular resistance, intrapulmonary shunting, clotting studies, or extravascular lung water. One of the five subjects in the placebo group died and two of the five subjects in the dazoxiben group died. We conclude that dazoxiben was safe and effectively lowered plasma iTxB2 levels in patients with sepsis and incipient adult respiratory distress symptom, but did not significantly alter the hemodynamic and pulmonary sequelae of established sepsis.
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PMID:Dazoxiben in human sepsis and adult respiratory distress syndrome. 397

The case of a pregnant patient with diffuse scleroderma who died following Caesarean section under general anaesthesia is presented. The patient's postoperative course was complicated by pulmonary oedema and pulmonary hypertension, sepsis, thrombocytopenia and renal failure. Aspects of the disease which possess anaesthetic implications are reviewed.
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PMID:Scleroderma and pregnancy. Anaesthetic considerations. 405 5

Acute respiratory failure (ARF) related to sepsis continues to have a high mortality and uncertain pathogenesis. With a reproducible live Pseudomonas aeruginosa infusion pig model, the gas exchange, hemodynamics, and pulmonary clearance of this organism were compared with live Staphylococcus aureus and Escherichia coli. Lightly anesthetized, male, mixed-breed pigs, 15-30 kg, were intubated, allowed to breathe spontaneously, and had femoral artery, central venous, and Swan-Ganz catheterization through cutdowns. After baseline data were collected, approximately 1 X 10(9) organisms/20 kg/min were infused into a central vein for 4 hr with frequent monitoring of the variables. Immediate autopsies were done for related quantitative tissue culture studies. S. aureus pigs maintained a high rate of lung bacterial clearance with pulmonary hypertension, a nonsignificant decrease in PaO2, and relatively normal lungs at autopsy. Ps. aeruginosa and E. coli animals developed systemic hypotension, pulmonary hypertension, increased pulmonary vascular resistance, hypoxemia, and decreased pulmonary clearance. Their lungs had gross congestion and edema. These studies confirm the suitability of E. coli and Ps. aeruginosa infusion into pigs as a model of sepsis-induced ARF in man. The findings also indicate that neither pulmonary hypertension nor bacterial clearance by the lungs is sufficient to cause ARF.
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PMID:Comparison of live bacteria infusions in a porcine model of acute respiratory failure. 633 4

The lung is very susceptible to sepsis or endotoxin injury in the trauma patient. We studied the effect of an episode of hemorrhagic shock and resuscitation on the prostaglandin-induced pulmonary hypertension and leukocyte-induced increased permeability phase of endotoxin lung injury. Eight unanesthetized sheep with chronic lung lymph fistula were bled 50% of blood volume for 2 hr, then resuscitated. Thromboxane, TxA2, levels increased from 0.1 to 0.6 ng/ml during shock, while blood white cell count decreased. Both parameters returned to baseline while lung lymph flow increased twofold during resuscitation with lymph being protein-poor, indicating no increase in permeability. Lung water was not increased but some pulmonary leukostasis was evident histologically after resuscitation. We then studied the effect of this process on all immediate endotoxin insult. Seven unanesthetized sheep were given 0.7 microgram/kg E. coli endotoxin alone, and again after shock and resuscitation, in paired studies performed 3 days apart. There was no difference in either the early pulmonary hypertension or the later increased permeability phase of endotoxin lung injury when comparing the paired studies, as measured by lymph flow and protein flux. Hemorrhagic shock, despite producing a transient increase in thromboxane and pulmonary leukocyte sequestration, does not accentuate the lung injury of endotoxin if the shock state is adequately resuscitated.
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PMID:Effect of hemorrhagic shock on endotoxin-induced pulmonary hypertension and increased vascular permeability in unanesthetized sheep. 636 38

Peripheral edema, hypoproteinemia, and increased fluid requirements are characteristically seen with sepsis. Our purpose was to determine whether the soft tissue edema is caused by a direct vascular injury from sepsis or is secondary to hypoproteinemia. We determined the effect of endotoxin on peripheral (soft tissue) microvascular integrity using lymph flow (QL) and lymph/plasma (L/P) protein ratio to reflect fluid flux and increased permeability. Response was compared with that seen in the lung. Fourteen unanesthetized sheep were given intravenous E. coli endotoxin 2 micrograms/kg. Vascular pressures and cardiac output (CO) were maintained constant with the necessary fluid infusion. Lung QL increased two- to fourfold in all animals with lymph being protein-rich, indicating increased permeability. Peripheral QL increased transiently in response to an initial increase in vascular pressure returning rapidly to baseline except in those animals (N = 5) demonstrating hypoproteinemia where QL remained increased by 50 to 75%. The increased QL was totally explained by the degree of protein depletion, with no evidence of increased permeability. To assure an adequate endotoxin exposure to the peripheral microvessels, endotoxin (2 micrograms/kg) was also directly injected into the tissue drained by the soft tissue lymphatic. We noted a characteristic endotoxin pulmonary hypertension phase but, again, no increase in peripheral microvascular permeability was found. We conclude that endotoxemia does not alter peripheral microvascular permeability if tissue perfusion is maintained, while the lung is clearly a target organ. Hypoproteinemia may be responsible for the early edema in soft tissues with sepsis.
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PMID:Effect of endotoxin on the integrity of the peripheral (soft tissue) microcirculation. 637 Apr 90


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