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

Platelet activating factor (PAF) is considered a key mediator in eliciting the immunologic and metabolic consequences of endotoxic shock and sepsis. Release of oxygen-derived radicals is one of the important and relevant actions of PAF. This study examines the direct and priming effects of PAF on superoxide anion release by perfused liver, isolated Kupffer cells and blood neutrophils. One hour after PAF infusion at a dose of 2.2 micrograms/kg body weight a significant amount of superoxide release (0.71 +/- 0.1 nmol/min/g liver) was measured in the perfused liver compared with the control livers (0.2 +/- 0.01). In the in vitro presence of either phorbol ester or opsonized zymosan, superoxide release following PAF treatment in vivo was significantly increased to 1.36 +/- 0.2 and 4.29 +/- 0.36, respectively. The administration of PAF receptor antagonist (SDZ 63-441) almost completely inhibited the release of this radical. Kupffer cells (KC1, KC2, KC3) and blood neutrophils isolated from PAF-treated rats were also primed for increased production when these cells were challenged in vitro by the activator of protein kinase C, opsonin-coated zymosan as well as the chemotactic factors, complement 5a and F-met-leu-phe. PAF added in vitro to the perfused livers, isolated Kupffer cells or neutrophils from normal animals stimulated the release of superoxide with or without the above agonists. The direct stimulatory effect of PAF on superoxide release was inhibited by the PAF receptor antagonist in vitro. The role of PAF in the LPS-induced superoxide release by the perfused liver was also examined by the administration of PAF antagonist in endotoxic rats. The antagonist inhibited the LPS-mediated superoxide release at 1 hr, but not at 3 hr post-treatment. These results indicate that PAF stimulates and primes the hepatic elements to release superoxide. PAF may be an important factor during the early phase of endotoxemia, while other bioactive substances may take over at a later phase. Therefore, PAF is a key mediator that can directly enhance the release of toxic oxygen-derived radicals which may contribute to organ failure during endotoxemia or sepsis.
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PMID:Platelet activating factor stimulates and primes the liver, Kupffer cells and neutrophils to release superoxide anion. 133 36

From previous studies it has been hypothesized that multiple organ failure and high level of mortality, seen in critically ill septic patients, may be due to defective oxygen extraction and tissue hypoxia occurring early in the course of sepsis. Oxygen flux test has been proposed as a method of revealing an occult oxygen debt. We used a one hour dobutamine infusion test, in septic patients, without increase in blood lactate. Fifty patients with sepsis syndrome entered a multicentric prospective study. After fluid loading to increase pulmonary artery occlusion pressure (Paop) to a minimum value of 10 mmHg, all the patients were given 10 mcg/kg.min of dobutamine for one hour. Hemodynamic and metabolic variables were recorded before, HO, and after the test, H1 (cardiac index, Paop, oxygen deliver, DO2, and consumption, VO2, oxygen extraction ratio, (OER), blood lactate). The dobutamine test allowed to identify responders (R) who increased VO2 by more than 15% and non-responders. R and NR differed significantly in mortality (8.5% vs 44.4%). The test has a good predictive value for surviving. Without respect of the result of the test, the patients were randomized in two groups. The group D+ was given conventional therapy and dobutamine at the same rate of infusion for 9 consecutive days and the D- group received only conventional therapy. The RD+ patients improved more rapidly when compared with RD-, NRD+, NRD-. We concluded that a one hour dobutamine test is able to identify R and NR critically ill septic patients. The response is associated with significant difference in outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Relation between oxygen delivery and consumption during septic states. Value of an early dobutamine test]. 134 94

Acute respiratory failure in pregnancy is an important cause of maternal and fetal morbidity and mortality. Causes include: ARDS, venous air embolism, beta-adrenergic tocolytic therapy, asthma, thromboembolic disease, pneumothorax, and pneumomediastinum. The most common predisposing diseases for ARDS complicating pregnancy are sepsis, pneumonia, aspiration of gastric contents, and amniotic fluid embolism. Knowledge of normal maternal-fetal physiology and determinants of fetal oxygen delivery (uterine blood flow, placental transfer, fetal circulation) can help sustain normal fetal development, usually without compromising maternal care. The increased microvascular permeability seen in ARDS is likely mediated by neutrophils, proinflammatory mediators (e.g., tumor necrosis factor, interleukin-1, arachidonic acid metabolites) and activation of the complement cascade. Treatment of respiratory failure in pregnancy is largely supportive, including mechanical ventilation, hemodynamic support, nutrition, and prophylaxis against thromboembolism. No specific therapy has as yet been proven effective for ARDS, other than treating the underlying cause. Respiratory failure from status asthmaticus is treated with vigorous bronchodilator therapy, high-dose glucocorticosteroids, magnesium sulfate, and careful ventilator management. Occasionally, more experimental therapies (e.g., isoproterenol infusion, halothane anesthesia) are indicated. Certain strategies can help prevent respiratory failure from aspiration of gastric contents, beta-adrenergic tocolytic therapy, and thromboembolic disease.
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PMID:Acute respiratory failure in pregnancy. 136 44

Inhibitors of nitric oxide synthase (NOS) have been reported to increase mean arterial pressure in animal models of sepsis and recently have been given to patients in septic shock. However, controlled studies to determine the effects of these agents on cardiovascular function and survival in awake animal models of sepsis have not been reported. To examine the therapeutic potential of NOS inhibition in septic shock, we challenged canines with endotoxin (2 or 4 mg/kg i.v.) and treated them with either normal saline or N omega-amino-L-arginine (10 or 1 mg/kg/h), the most specific inhibitor available for the isoform of NOS implicated in septic shock. Endotoxemic animals treated with N omega-amino-L-arginine (n = 11) had higher systemic and pulmonary vascular resistance indices (SVRI and PVRI, p less than or equal to 0.033) and decreased heart rates (p = 0.009), cardiac indices (CI, p = 0.01), oxygen delivery indices (p = 0.027), and oxygen consumption indices (p = 0.046) compared with controls (n = 6). Moreover, N omega-amino-L-arginine increased mortality rates after endotoxin challenge (10 of 11 vs. 1 of 6 controls, p = 0.005). Administration of L-arginine did not improve survival or alter the cardiopulmonary effects of N omega-amino-L-arginine, which suggests that inhibition of NOS may not have been competitive. In normal animals, N omega-amino-L-arginine alone (n = 3) increased SVRI (p = 0.0008) and mean arterial pressure (p = 0.016), and decreased CI (p = 0.01) compared with saline-treated controls (n = 3), but, at the high dose, also produced neuromuscular rigidity and seizure-like activity that was not apparent in the endotoxemic model. Thus, the mortality rate from endotoxemia increased either because of NOS inhibition per se or because of properties unique to N omega-amino-L-arginine, or both.
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PMID:N omega-amino-L-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin. 138 77

Tissue oxygenation in the gastrointestinal tract was studied in a porcine model in which septic shock was induced by fecal peritonitis. The oxygen delivered was estimated by measuring the portal venous blood flow and the calculated arterial oxygen saturation. The oxygen consumption of the gut, including the pancreas and spleen, was monitored by measuring the portal venous blood flow and the difference between the calculated arterial oxygen and the measured portal venous oxygen saturation. In addition, the oxygenation of the gut mucosa was followed via the tonometric technique. Furthermore, lactate was measured in arterial and portal blood. The experimental animals were divided into two groups, one control (n = 6) and one experimental (n = 6). Peritonitis was introduced by installation of a standardized amount of autologous feces into the abdominal cavity. The animals were followed for 5 hr. Very early during the course of sepsis there was a fall in gut intramucosal pH (pHi), and this was evident before any reduction in splanchnic DO2. Furthermore, an early increase in splanchnic VO2 was evident simultaneously with the fall in pHi. Arterial pH and lactate were not able to detect the inadequate regional tissue oxygenation. It is concluded that pHi measured with the tonometric technique is sensitive in detecting gut mucosal ischemia, and it is therefore highly likely that tonometry would be a valuable method in monitoring severe ill patients.
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PMID:Early gut ischemia in experimental fecal peritonitis. 139 60

Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction that characterizes Gram-negative sepsis. In animal models of endotoxemia, pretreatment with ibuprofen or pentoxifylline attenuates some of these cardiovascular changes. To evaluate the effects of these agents on the human cardiovascular response to endotoxemia, hemodynamic variables were measured serially in 24 normal subjects who were given intravenous endotoxin. The subjects were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no medication before endotoxin administration (n = 5). The subjects were volume loaded 3-5 h after endotoxin administration, and hemodynamic measurements were reassessed. Core temperature after endotoxin alone or endotoxin-pentoxifylline approached a maximum at 3 h (greater than or equal to 38.6 degrees C), while the endotoxin-ibuprofen group remained afebrile. At 3 and 5 h, all three groups had significant increases in heart rate, cardiac index, oxygen delivery, and oxygen consumption, while systemic vascular resistance index decreased significantly from baseline. The oxygen extraction ratio remained unchanged. After volume loading, the left ventricular ejection fraction and left ventricular end-diastolic and end-systolic volume indexes did not differ among the groups. The hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence of fever and is not significantly ameliorated by oral cyclooxygenase or phosphodiesterase inhibition.
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PMID:Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin. 140 57

Under normal conditions the intestinal mucosa is impermeable to potentially harmful materials from the intestinal lumen. Mucosal disruption promotes bacterial translocation, which is postulated to be a fuel source for sepsis and multiorgan failure. We have previously demonstrated that mesenteric ischemia-reperfusion (I/R) injury increases intestinal permeability (IP); however, the mechanism remains unclear. This study was designed to examine the hypothesis that changes in IP, after I/R injury, are mediated by xanthine oxidase-generated, oxygen-derived free radicals. Thirty-three Sprague-Dawley rats (weighing 300 to 400 g) were included in this study. Group 1 (n = 10) received enteral allopurinol, a xanthine oxidase inhibitor, 10 mg/kg daily for 1 week prior to mesenteric ischemia. Group 2 consisted of 11 untreated, ischemic animals. Groups 1 and 2 were subjected to superior mesenteric artery occlusion with interruption of collateral flow for 20 minutes to produce ischemic injury to the intestine. An additional 12 rats (group 3), served as nonischemic controls (sham). A loop of distal ileum was isolated and cannulated proximally and distally to allow luminal perfusion with warmed Ringer's lactate at 1 mL/min. IP was determined in all groups by quantitatively measuring the plasma-to-luminal clearance of chromium (51Cr)-labeled ethylenediaminetetraacetate (EDTA) at baseline, during ischemia and 20, 40, and 60 minutes after reperfusion. Complete ischemia produced significant increases in IP over baseline values in the untreated rats (group 2, baseline: 0.49 +/- 0.006, ischemia: 0.149 +/- 0.039) compared with sham rats (baseline: 0.41 +/- 0.006; ischemia: 0.047 +/- 0.009) or allopurinol-treated rats (baseline: 0.098 +/- 0.020, ischemia: 0.073 +/- 0.012, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allopurinol prevents intestinal permeability changes after ischemia-reperfusion injury. 140 60

Because hypoxia is one of the most common major stresses to which a neonate is exposed, we postulated that it alone might be the cause of intestinal bacterial translocation, which could be the underlying etiology of neonatal sepsis. An animal model, in which hypoxia is the sole stress, was developed in our laboratory and tested in 18 puppies to determine the effect of hypoxia and reoxygenation on intestinal bacterial translocation. In group I (n = 8), following laparotomy and cannulation of the superior mesenteric vein (SMV), the FIO2 was decreased from 21% to 9% for 90 minutes followed by reoxygenation at 21% for 120 minutes. The abdomen was closed and the animals were allowed to recover. After 24 hours the mesenteric lymph nodes (MLNs), spleen, and liver were harvested for bacterial determination and the ileum and jejunum for histological evaluation. Group II (n = 7) was treated the same as group I with the FIO2 maintained at 21%. Group III (n = 3) animals were killed, without intervention, for bacterial analysis. In group I, the systemic PO2 decreased by 75%, SMV PO2 decreased by 64%, and oxygen delivery to the small bowel decreased by 80% in comparison with group II. The mean arterial pressure and cardiac output were not significantly different between group I and group II; however, the mucosal blood flow was decreased by 60% (P less than .001) in group I. Arterial and SMV blood lactic acid levels were unchanged in group I in comparison with group II, suggesting that anaerobic metabolism was not initiated in the splanchnic circulation during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoxia-induced bacterial translocation in the puppy. 140 61

One hundred ten infants with congenital diaphragmatic hernia (CDH) developed life-threatening respiratory distress in the first 6 hours of life. Associated anomalies were present in 33%. Twenty-eight of 65 infants (43%) treated before 1987 (pre-extracorporeal membrane oxygenation [ECMO] era) survived after immediate CDH repair, and mechanical ventilation with or without pharmacologic support. Only two of 16 (12.5%) infants requiring a prosthetic diaphragmatic patch survived. Since 1987, 31 of 46 (67.4%) infants with birth weight, gestational age, and severity of illness similar to the pre-1987 group survived. All patients were immediately intubated and ventilated. Seven (four with lethal chromosomal anomalies) infants died before treatment, and 30 stabilized (partial pressure of carbon dioxide [PCO2] < 50; partial pressure of oxygen [PO2] > 100; pH > 7.3) and underwent delayed CDH repair at 5 to 72 hours. Fifteen did well on conventional support and survived. Fifteen infants deteriorated after operation: 11 were placed on ECMO with eight survivors, and four infants were not considered ECMO candidates. Nine babies failed to stabilize initially and were placed on ECMO before CDH repair (alveolar-arterial gradient > 600 and oxygenation index > 40), and seven survived. The overall survival rate was 80% at 3 months in this ECMO-treated group. Early mortality was due to inability to wean from ECMO (one), intracranial hemorrhage (one), liver injury (one), and pulmonary hypoplasia (one). Nine of 11 babies requiring a prosthetic patch in the post-1987 ECMO group survived (81.8%). There were three late post-ECMO deaths (3 to 18 months) of right heart failure (two) and sepsis (one). Symptomatic gastroesophageal reflux occurred in nine cases, six requiring a fundoplication in the bypass babies. Recurrent diaphragmatic hernia occurred in nine cases (five ECMO). The overall survival rate was significantly improved in the delayed repair/ECMO group (67% versus 43%; p < 0.05) and was most noticeable in infants requiring a prosthetic diaphragm (81.2% versus 12.5%; p < 0.005). These data indicate that early stabilization, delayed repair, and ECMO improve survival in high-risk CDH. Early deaths are related to pulmonary hypertension and can be reversed by ECMO.
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PMID:Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia. 141 95

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.
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PMID:Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease. 141 90


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