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

Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR). For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased. In survivors, these abnormalities reverse to normal within 7 to 10 days. The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia. In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high-energy stores, or abnormal myocardial oxygen utilization. However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury. The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time. The pathophysiology of this disease is complex. Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock. Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate. Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease.
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PMID:Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock. 151 2

The chemiluminescence of isolated neutrophils, stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine, latex, lipopolysaccharide from Escherichia coli, zymosan A, or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was inhibited up to 99% by the dose-dependent oxygen radical scavenging activity of 6 mmol/l ascorbic acid. The chemiluminescence of neutrophils in blood, stimulated with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, or with zymosan A was inhibited 35% or 48%, respectively, by 6 mmol/l ascorbic acid. Ascorbic acid, up to 6 mmol/l, did not inhibit the release of beta-N-acetylglucosaminidase and elastase from isolated neutrophils activated by the above stimulatory agents. During neutrophil/nylon fibre interaction ascorbic acid reduced the oxygen radical production dose-dependently (77% inhibition of the chemiluminescence response at 6 mmol/l ascorbic acid), whereas the adherence was unaffected. Hypoxanthine/xanthine oxidase-generated oxygen radicals were scavenged by ascorbic acid in a dose-dependent manner (99% inhibition of the chemiluminescence response at 100 mumol/l ascorbic acid). From these results, ascorbic acid can highly be recommended for animal experiments and clinical studies in patients with trauma, shock and sepsis and for studies to prevent or reduce reperfusion injuries.
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PMID:Effect of ascorbic acid on neutrophil functions and hypoxanthine/xanthine oxidase-generated, oxygen-derived radicals. 152 46

The purpose of the study reported here was to characterize the effects of acute exposure to 100% oxygen at a pressure of 202.6 kPa on hemodynamics and organ blood flow in antibiotic-controlled bacterial sepsis. An abscess containing known numbers and strains of live Escherichia coli and Bacteroides fragilis was established in the peritoneal cavity of rats. Sham-operated rats were used as controls. Cardiac output, fractional blood flow distribution, and blood flow were calculated from data obtained using the radiolabeled microsphere technique. Myocardial and renal blood flows were decreased (20-30%) in both experimental groups during hyperbaric oxygen (HBO) exposure. Renal blood flow remained diminished for at least 20 min after rats were removed from the hyperbaric chamber. Adrenal gland perfusion in abscess-containing rats was reduced both during and after HBO exposure. Skeletal muscle blood flow (quadriceps and gastrocnemius muscles) was reduced by one third in both experimental groups 20 min after acute exposure to HBO. The results of this study indicate that changes in organ perfusion induced by HBO are similar in abscess-containing and normal rats. We conclude that HBO does not alter the regulation of blood flow in antibiotic-controlled sepsis.
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PMID:Hyperbaric oxygenation decreases blood flows in normal and septic rats. 153 61

To investigate the mechanism of metabolic acidosis resulting from group B streptococcal sepsis, oxygen metabolism and lactate flux of the cerebrum, hindlimb, liver, splanchnic organs, and systemic vascular bed as a whole were examined. Nine 3- to 5-day-old awake and spontaneously breathing piglets were studied before and after 3, 4, and 5 h of continuous live group B Streptococcus infusion. After 5 h, oxygen delivery was decreased to all organs and to the whole systemic vascular bed. Increased oxygen extraction compensated for reduced oxygen delivery in the liver and splanchnic organs; however, it only partially offset reduced oxygen delivery to the hindlimb and systemic vascular bed. Cerebral oxygen extraction did not increase. As a result, oxygen uptake was reduced in the cerebrum, hindlimb, and systemic vascular bed. At 5 h of bacterial infusion, arterial lactate concentration was increased with regional lactate efflux from the cerebrum and hindlimb and influx to the liver (P less than 0.05 vs. zero or no net flux). We conclude that group B Streptococcus-induced metabolic acidosis is associated with regional lactate efflux from vascular beds in which oxygen uptake is reduced. We speculate that the quantity of net lactate efflux from vascular beds with insufficient oxygen uptake exceeds the net influx into organs such as the liver, resulting in metabolic acidosis.
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PMID:Group B Streptococcus-induced acidosis in newborn swine: regional oxygen transport and lactate flux. 153 25

Sepsis is frequently characterized by a number of metabolic abnormalities: increased plasma lactate concentration, metabolic acidosis, increased glycolysis, and an abnormal "delivery-dependent" oxygen consumption. Two hypotheses have been advanced to explain these metabolic abnormalities: (1) cellular hypoxia resulting from abnormal microcirculatory blood flow or (2) defect(s) in energy-producing metabolic pathways of cells. Results of our studies on rat muscle, liver, heart, brain, and plasma suggest that there is no evidence of bioenergetic failure in these septic tissues and that the increase in lactate production is not necessarily due to cellular hypoxia. The adequacy of cellular oxygenation and bioenergetics was verified using in vivo phosphorus 31 nuclear magnetic resonance spectroscopy, [18F]fluoromisonidazole, and microfluorometric enzymatic techniques. Findings from these studies as well as results from several clinical investigations indicate that neither hypothesis can adequately account for the metabolic features typical of sepsis and that the pathophysiology of sepsis awaits further clarification. These studies and important clinical implications are discussed.
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PMID:Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. 153 43

From 1987 to February 1991, we have repaired or replaced the aortic arch in ten patients using deep hypothermic systemic circulatory arrest with continuous retrograde cerebral perfusion (CRCP). CRCP can be implemented using the bypass connecting the arterial and venous lines of the extracorporeal circuit to reverse the flow into the superior vena cava cannula after induction of circulatory arrest. CRCP flow required to maintain an internal jugular vein pressure of 20 mmHg ranged from 100 to 500 ml/min. After completion of suturing of the aortic arch graft, air is evacuated retrogradely from the open arch vessels prior to reestablishing the usual arterial return. Two patients died, one from sepsis and the other from liver cirrhosis 1 month postoperatively. CRCP times ranged from 11 to 56 min, and minimal nasopharyngeal temperatures ranged from 16 degrees to 18 degrees C. The difference in oxygen content between the perfused blood and the blood draining from the arch vessels during CRCP most likely reflected the steady-state metabolism of the brain during the deep hypothermic state. This technique offers advantages including the need for dissecting and clamping the arch branches, providing sufficient metabolic support to the brain during deep hypothermia, and eliminating embolism of particulate debris from the aortic arch.
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PMID:Deep hypothermic systemic circulatory arrest and continuous retrograde cerebral perfusion for surgery of aortic arch aneurysm. 154

TNF is a major mediator in the pathogenesis of endotoxic shock, and its inhibition has a protective effect in various animal models of sepsis or endotoxin (lipopolysaccharide, LPS) toxicity. LPS treatment also induces an oxidative damage mediated by increased production of reactive oxygen intermediates. N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH) and was reported to protect against LPS toxicity and LPS-induced pulmonary edema. In this study we investigated the effect of NAC on TNF production and LPS lethality in mice. The results indicated that oral administration of NAC protects against LPS toxicity and inhibits the increase in serum TNF levels in LPS-treated mice. The inhibition was not confined to the released form of TNF, since NAC also inhibited LPS-induced spleen-associated TNF. On the other hand, the inhibitor of GSH synthesis, DL-buthionine-(SR)-sulfoximine (BSO), had the opposite effect of potentiating LPS-induced TNF production, and this was associated with a decrease in liver GSH levels. Repletion of liver GSH with NAC reversed this effect. NAC was also active in inhibiting TNF production and hepatotoxicity in mice treated with LPS in association with a sensitizing dose of Actinomycin D. These data indicate that GSH can be an endogenous modulator of TNF production in vivo. On the other hand, NAC pretreatment did not inhibit other effects of LPS, particularly induction of serum IL-6, spleen IL-1 alpha, and corticosterone, in the same experimental model, suggesting that the observed effect could be specific for TNF.
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PMID:N-acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. 154 68

From July 1988 to March 1991, extracorporeal membrane oxygenation (ECMO) was used in 8 infants (newborn to 16 months old) with unoperated cyanotic congenital heart disease and cardiopulmonary collapse, associated with hypercyanotic spells (4 infants), pulmonary hypertensive crises (3) and sepsis (1). Indications for ECMO support were arterial saturations less than or equal to 60% accompanied by hypotension and metabolic acidosis unresponsive to mechanical ventilation with 100% oxygen, paralysis and sedation, and pharmacologic support with inotropes or vasodilators, or both. Venoarterial bypass by carotid/jugular cannulation with flow rates of 100 to 840 ml/kg/min (mean 460) stabilized all patients. Duration of ECMO support ranged from 15 to 840 hours and was associated with transient seizures (1 patient) and renal failure (1). Seven patients underwent palliative (3 patients) or corrective (4) surgical procedures while on ECMO or within 48 hours of decannulation, including 1 patient bridged to double-lung transplantation with a long (840 hours) duration of ECMO. There was 1 operative and 2 late (greater than 1 month after decannulation) deaths, for an overall survival rate of 62%. These 5 survivors all have normal growth and development, and patent neck vessels at the site of cannulation. These early results indicate that ECMO can be effective mechanical support in cardiovascular crises untreatable with maximal conventional medical therapy and can be used as a bridge to successful surgical palliation or repair.
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PMID:Extracorporeal life support in cyanotic congenital heart disease before cardiovascular operation. 154 55

The relationship between outcome and hemoglobin (Hgb), oxygen extraction ratio (ER), history of cardiac, renal, pulmonary, and/or hepatic disease, diabetes, malignancy, sepsis, hypertension, and active bleeding was analyzed in 47 patients with severe anemia (Hgb less than 7.0 gm/dl, mean = 4.6 +/- .2 gm/dl) to evaluate the effect of Hgb on survival and to look for other predictors of outcome. All patients had refused blood transfusion on religious grounds and were participants in a randomized, controlled study of the blood substitute Fluosol DA-20 per cent. Patients were analyzed as a group and after stratifying by Hgb into four levels: (Hgb less than 3.0 gm/dl, N = 7; Hgb less than 3.5 gm/dl, N = 12; Hgb less than 4.0 gm/dl, N = 17; Hgb less than 4.5 gm/dl, N = 23) and by ER into two levels of less than 50 per cent and greater than 50 per cent. Only Hgb, ER, sepsis and active bleeding were predictors of outcome, with sepsis being the only significant, independent predictor of outcome at all levels (P less than .01). Active bleeding was a predictor for levels of Hgb below 4.0 gm/dl. Hgb level alone was a significant predictor only at levels below 3 gm/dl (P less than .05). Extraction ratio interacted with Hgb only below 3 gm/dl (P less than .05). Multiple independent factors influence outcome in the severely anemic patient, the strongest being sepsis and active bleeding. Prevention of sepsis and early intervention to stop bleeding should improve survival in the patient who refuses transfusion.
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PMID:Is hemoglobin level alone a reliable predictor of outcome in the severely anemic surgical patient? 155 Mar 12

Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiology in human newborns and neonatal animal models of sepsis. Animal models of GBS sepsis demonstrate a two-phase response: 1) an acute phase (less than 1 h) of increased pulmonary artery pressure (Ppa) and reduced arterial oxygen pressure (PaO2) that is associated with increased serum thromboxane B2 (TxB2) and 2) a late phase (2-4 h) of persistently increased Ppa and reduced PaO2, reduced systemic arterial pressure, and progressive fall in cardiac output that is associated with increased serum TxB2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and tumor necrosis factor-alpha (TNF alpha). We hypothesized that pretreatment of piglets with both pentoxifylline (PTF), an inhibitor of TNF alpha production and activity, and indomethacin (INDO) would 1) inhibit GBS-induced TxB2, 6-keto-PGF1 alpha, and TNF alpha and 2) prevent both the acute- and late-phase physiologic responses of GBS sepsis. Combined PTF and INDO pretreatment of anesthetized, mechanically ventilated piglets infused with GBS (1.25 x 10(9) colony forming units/kg/h) for 4 h prevented GBS-induced increases in Ppa at 1 h (GBS + PTF + INDO: 1.8 +/- 0.07 kPa versus GBS alone: 4.7 +/- 0.1 kPa) and markedly attenuated increases in Ppa at 4 h (GBS + PTF + INDO: 2.1 +/- 0.1 kPa versus GBS alone: 4.4 +/- 0.1 kPa).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Group B streptococcal sepsis in piglets: effect of combined pentoxifylline and indomethacin pretreatment. 156 Oct 7


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