Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Comparison of live bacteria infusions in a porcine model of acute respiratory failure. 633 4

Infusion of Escherichia coli endotoxin into sheep causes a syndrome analogous to the adult respiratory distress syndrome. Physiologic measurements show an initial phase of marked pulmonary hypertension followed by a phase characterized by the production of large quantities of protein-rich lung lymph. The present study relates the structural changes that occur during endotoxemia to concomitant functional changes. In five anesthetized open-chest sheep, we monitored pulmonary and systemic artery pressure for a 1 hour baseline period and for 4 hours after the start of E. coli endotoxin infusion (1.25 microgram/kg, intravenously). We also measured cardiac output, arterial blood gases and pH, and number of circulating leukocytes. In addition, we sequentially biopsied random lobes from the lungs of each sheep at baseline and at 15, 30, 60, 120, 180, and 240 minutes after the start of endotoxin. Five control sheep were treated identically except that they received saline instead of endotoxin. By 15 minutes after the start of endotoxin infusion, light microscopy revealed margination and accumulation of leukocytes in the lungs' microcirculation. Counts of the number of peripheral lung granulocytes in biopsy specimens showed a 3-fold increase above baseline by 15 minutes and a 6-fold increase by 4 hours. By electron microscopy, the leukocytes were identified as both granulocytes and lymphocytes, present in approximately equal numbers. Some granulocytes were fragmented, and specific granules were found free in the vessel lumen. By 30 minutes, some leukocytes were migrating into the interstitium. By 60 minutes, interstitial edema was seen, and there was focal endothelial cell damage. Correlation of the structural with the physiologic changes shows that the initial accumulation of leukocytes in the microcirculation occurs when pulmonary hypertension develops. The migration of leukocytes into the interstitium and endothelial cell damage precedes the physiologic changes that we interpret as increased pulmonary vascular permeability. Since gram negative septicemia is a frequent occurrence in the adult respiratory distress syndrome the changes described here may be similar to the alterations that occur early in the development of the syndrome in man.
 ...
PMID:Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep structure:function relationships. 633 12

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.
 ...
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.
 ...
PMID:Effect of endotoxin on the integrity of the peripheral (soft tissue) microcirculation. 637 Apr 90

Using a piglet model of neonatal sepsis, we have determined that Group B streptococcal (GBS) bacteremia is associated with a state of vascular hyper-resistance in both the pulmonary and systemic circulations. This elevated vascular resistance is accompanied by a significant fall in cardiac output despite the assurance of constant intravascular fluid volume. Pulmonary artery pressure rises extensively while systemic blood pressure remains essentially unchanged during this GBS infusion protocol. We report here our attempts to relieve the vascular hyperresistance of GBS infusion by administration of an alpha-sympathetic antagonist, tolazoline (Tz). We found that Tz, in a dose-related fashion, decreased both systemic and pulmonary vascular resistance over the entire range from 2 to 25 mg/kg. Further, at all doses tested, the resistance-reducing effect of Tz was equal in the systemic and pulmonary vascular beds. No selective pulmonary or systemic vasodilatory effect was demonstrated by Tz in this model of neonatal pulmonary hypertension. The reduction of systemic vascular resistance was accompanied by a significant elevation in total body cardiac output at all Tz doses. Compared to pre-Tz values, cardiac output rose by 24, 55, and 55% after Tz at 2, 8.3, and 25 mg/kg respectively. In addition, administration of Tz to septic normovolemic piglets reliably produced a transient decrease of systemic blood pressure. For Tz doses of 2 and 8.3 mg/kg, steady state systemic blood pressure returned to pre-Tz levels within 10 min. However, after Tz at 25 mg/kg, steady state systemic blood pressure remained significantly below pre-Tz levels.
 ...
PMID:Hemodynamic consequences of tolazoline in neonatal group B streptococcal bacteremia: an animal model. 638 8

Ventriculoatrial shunts were first developed in the 1940s and shortly thereafter became the treatment of choice for noncommunicating hydrocephalus. Although the mortality rate for noncommunicating hydrocephalus has fallen from 80% to 20%, ventriculoatrial shunts continue to have major life-threatening complications such as thromboemboli, infection, and shunt malfunction. This report presents the cases of two adult hydrocephalic patients who developed pulmonary emboli and sepsis after being treated with ventriculoatrial shunts. One patient, whose complications were not recognized until late in the course, died of pulmonary hypertension and right heart failure despite removal of the shunt and aggressive medical therapy. Complications in the second patient were discovered early, the shunt was removed, and intravenous antibiotics were used for weeks to combat sepsis and bacterial endocarditis.
 ...
PMID:Thromboembolic complications of ventriculoatrial shunts. 649 51

Two of 30 patients with esophageal varices had respiratory distress develop within 8-24 h of esophageal sclerotherapy. Evidence of aspiration and sepsis were absent in these two patients with the clinical picture of adult respiratory distress syndrome. To investigate the possible etiologic role of sodium morrhuate in this syndrome, a sheep model was established and pulmonary hemodynamics, lung lymph flow, and albumin concentration were measured before and after the intravenous injection of 2.5-15.0 cm3 of sodium morrhuate. In all 8 animals studied, mean pulmonary artery pressures increased from 11.6 +/- 2.8 to 32.8 +/- 4.9 mmHg (p less than 0.01) 30 s after injection. These pressures returned to baseline values over 120 min. Lymph flow increased from 0.91 +/- 0.89 to 2.8 +/- 1.5 ml/30 min at 90 min postinjection (p less than 0.05) and returned to baseline values in animals monitored for 6-8 h. The lymph/plasma albumin ratio decreased from 0.856 +/- 0.08 to 0.74 +/- 0.01 (p less than 0.05) 120 min postinjection. Pulmonary edema was not evident histologically or gravimetrically (wet/dry weight ratio was 3.65 +/- 0.3 and not different from normal). It was concluded that sodium morrhuate injection in sheep causes marked but transient pulmonary hypertension associated with an increased lymph flow of relatively protein-poor lymph. Sodium morrhuate esophageal sclerotherapy may affect pulmonary hemodynamics and contribute to respiratory difficulties in patients.
 ...
PMID:Acute respiratory failure after sodium morrhuate esophageal sclerotherapy. 660 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>