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

Our previous experimental studies showed that the liver is firstly and most severely involved in metabolic damage among various organs after hypoperfusion and sepsis. Changes of metabolites in liver and other organs as well as the function of circulating leukocytes were measured in three rat models with liver ischemia, or systemic hypoperfusion and sepsis. Partial liver ischemia 120 minutes after reperfusion not only resulted in significant decline of ATP and GSH levels in ischemic liver lobes but also in metabolic disorders in non-ischemic liver lobes, kidney, and small intestine. The amount of circulating white blood cells and zymosan stimulated chemoluminescence was increased. The findings showed that ischemic injury in partial liver may accelerate the whole liver damage and aggravate the metabolic disorders in other organs as well as the deterioration of homeostasis. Changes of liver sulfhydryl group levels and related metabolism were estimated. Significant decrease in liver sulfhydryl group levels during hypoperfusion and sepsis may contribute to various cellular metabolic disorders and destruction in early liver damage.
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PMID:[The liver in the pathogenesis of multiple organ failure]. 191 99

Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis. We employed the novel hypoxic marker [18F]fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat. A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion. No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats. Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs. 20% decrease, P less than 0.05) and an increased retention of [18F]fluoromisonidazole in skeletal muscle of the septic rats. We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis. The greater reduction in muscle blood flow and the increased retention of [18F]fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia.
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PMID:Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. 192 43

Diabetic patients exhibit a higher incidence of post-surgical sepsis, as well as a higher rate of mortality from sepsis, than their non-diabetic counterparts. This may be a result of cardiovascular deterioration associated with diabetes mellitus. This study was designed to characterize the cardiovascular sequelae associated with endotoxin shock in a canine model of diabetes. Diabetes was induced with alloxan (50 mg/kg) and streptozotocin (30 mg/kg) in dogs weighing 19-25 kg. Thirty days later, anaesthetized dogs were instrumented to obtain blood pressures, blood samples, left ventricular chamber diameter, circumflex arterial blood flow, and aortic blood flow. Metabolic parameters were calculated according to the Fick principle, and myocardial inotropic state assessed with the end-systolic pressure-diameter relationship. After stable baseline measurements, Escherichia coli endotoxin (1 mg/kg) was infused over 1 h, and measurements were obtained every 30 min. After endotoxin administration diabetic dogs became more hypotensive than the non-diabetic dogs. Cardiac performance parameters were also depressed to a greater degree. These changes could be attributed to depressions in vascular resistance and myocardial inotropic state in diabetic dogs. Cardiac dysfunction occurred in association with a relative decrease in the supply to demand ratio for oxygen in the diabetic dogs, suggesting functional ischemia. Data indicating a decrease in pre-load and vascular resistance in the diabetic group suggest a greater degree of vascular collapse, vascular pooling, or extravasation of fluid than occurred in the non-diabetic group. These data support the hypothesis that the cardiovascular system of diabetic subjects cannot tolerate a septic insult as well as their non-diabetic counterparts.
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PMID:Cardiovascular sequelae of endotoxin shock in diabetic dogs. 195

Secretory component was assayed in serum and bile from 34 patients within 40 days after a first or a second (three cases) liver transplantation. Levels of serum secretory IgA and IgM and of a serum component referred to as immunoreactive free secretory component, identified by its reactivity with monoclonal and polyclonal antibodies specific to secretory component, were significantly elevated in all posttransplant patients compared with 45 healthy subjects and 10 kidney transplant patients (p less than 0.0001). The highest serum levels of bound secretory component and of immunoreactive free secretory component were observed in patients with acute rejection. The elevation of immunoreactive free secretory component was significantly higher in patients with rejection as compared with patients with a graft ischemia (p = 0.002) or an uncomplicated postoperative evolution (p = 0.01). The highest levels of immunoreactive free secretory component and secretory IgM were observed in a transplant patient with selective IgA deficiency. No significant difference was seen between the levels of serum immunoreactive free secretory component observed in patients with rejection and those of patients with cytomegalovirus hepatitis or sepsis. Immunoreactive free secretory component, secretory IgA and secretory IgM levels measured in the serum of three patients with primary nonfunction were lower than those observed in the other groups. Immunoreactive free secretory component bile/serum ratios calculated from 16 patients were significantly higher in patients with acute rejection than in infected patients. This study provides new insight into the mechanisms of increase of serum immunoreactive free secretory component, secretory IgA and secretory IgM in various types of liver dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum and bile secretory immunoglobulins and secretory component during the early postoperative course after liver transplantation. 195 52

Sepsis has been reported to cause mitochondrial dysfunction and inhibition of key enzymes that regulate the tricarboxylic acid (TCA) cycle. We investigated the effect of sepsis on high-energy phosphates, glycolytic and TCA cycle intermediates, and specific amino acids that are involved in regulating the size of the TCA cycle pool during changes in metabolic state of the heart. Sepsis was induced in 12 female rats by the cecal ligation and perforation technique under halothane anesthesia; seven control rats underwent cecal manipulation without ligation. At 36-42 h postsurgery, the rats were reanesthetized, the chest was opened, and the hearts were freeze-clamped. Perchloric acid extracts of the hearts were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic resonance spectroscopy. There were no significant differences in the levels of the TCA cycle intermediates or high-energy phosphates between the septic and control rats. The major metabolic changes were the 28% decrease in alanine and the 31% decrease in glutamate in the septic hearts compared with control (P less than 0.05 and P less than 0.005, respectively). Phosphocholine, a component of membrane phospholipids, was increased by 91% in the septic hearts (P less than 0.01). We conclude that sepsis does not impair the TCA cycle or induce significant cellular ischemia in the heart. The increase in phosphocholine may represent significant cellular membrane disruption during sepsis.
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PMID:Sepsis does not impair tricarboxylic acid cycle in the heart. 198 81

Over a 57-month period, we performed 430 orthotopic liver transplants in 372 patients. A total of 38 vascular complications were identified including hepatic artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n = 5). A number of potential risk factors for the development of vascular thrombosis were evaluated with only children, weight less than 10 kg, and cold ischemia time found to be significant. The clinical presentation included fulminant hepatic failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex ultrasonography was diagnostic in nearly all cases. Therapeutic modalities included revascularization, revascularization followed by retransplantation, retransplantation alone, and observation. Five cases of hepatic artery rupture occurred in four patients. Infectious arteritis was present in four patients. The 6-month actuarial survival in patients with vascular complications was 70%. Early diagnosis is critical for graft salvage, with surgical intervention the mainstay of therapy.
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PMID:Vascular complications after orthotopic liver transplantation. 198 61

Monoclonal antibodies (MAbs) that recognize the neutrophil (PMN) adherence complex CD11/CD18 inhibit PMN adherence to endothelium and attenuate PMN-mediated ischemia-reperfusion injury. One consideration regarding the clinical usefulness of such therapy is whether transient inhibition of PMN adherence or function will impede host defense and increase susceptibility to infection and sepsis. We studied susceptibility to sepsis in New Zealand white rabbits with an appendiceal devascularization model to answer the question: Does inhibition of PMN adherence with the anti-CD18 MAb 60.3 increase morbidity and mortality rates in abdominal sepsis? Four treatment groups of 10 animals each were studied: group 1 (controls) received no treatment, group 2 received MAb 60.3, group 3 was given the antibiotic cefazolin alone, and group 4 received both cefazolin and MAb 60.3. PMN emigration into the peritoneum was inhibited significantly in MAb 60.3-treated animals (groups 2 and 4). There was no difference in weight loss, incidence of infectious complications, or mortality rates when MAb 60.3-treated animals were compared with untreated animals. These results demonstrate that transient inhibition of PMN adherence does not increase morbidity or mortality rates in this model of abdominal sepsis. These results suggest that if MAb 60.3 or similar antibodies are used to prevent PMN-mediated injury, they will not increase susceptibility to sepsis.
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PMID:Transient inhibition of neutrophil adherence with the anti-CD18 monoclonal antibody 60.3 does not increase mortality rates in abdominal sepsis. 200 54

Tumor necrosis factor (TNF) facilitates superoxide production, and spin traps may detoxify superoxide by acting as superoxide dismutase mimics. We investigated the ability of a stable nitroxide spin trap, TEMPOL, to protect TNF-sensitive cells from exogenously added TNF. WEHI or L929 cells were incubated with TNF (500 units/ml) for 18 hr either simultaneously with 0 to 8 mM TEMPOL or with the TEMPOL added at varying intervals after TNF exposure. A dose-dependent increase in survival was noted in the TEMPOL-treated cells, with 92 +/- 2% survival of WEHIs treated with 4 mM TEMPOL compared to 26 +/- 1% survival for non-TEMPOL-exposed cells (P2 less than 0.01). Significant increases in survival could be accomplished with as late as 15-hr delayed addition of the compound. The mechanism of protection does not seem to involve newly synthesized protein, and Northern blot analysis revealed that TEMPOL does not induce the genes for MnSOD or Cu-ZnSOD. The ability of TEMPOL to protect against TNF injury, even when exposure is delayed, may prove useful in conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion, oxygen toxicity, or sepsis.
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PMID:Spin trap protection from tumor necrosis factor cytotoxicity. 203 86

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.
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PMID:Differential pathophysiology of bacterial translocation after thermal injury and sepsis. 206 68

Transient episodes of gut mucosal ischemia occur in many patients having cardiac surgery. Ischemic mucosal injury increases mucosal permeability and promotes the translocation of bacterial toxins and bacteria and, hence, the release of mediators. Collectively these substances are the putative cause of LOS, nosocomial infections, and MSOF. Circumstantial evidence suggests that the morbidity and mortality from cardiac surgery might be greatly reduced by preventing or limiting in duration the episodes of gut mucosal ischemia. This objective is unlikely to be reliably achieved in clinical practice without monitoring the adequacy of gut mucosal oxygenation. The adequacy of gut mucosal oxygenation can be conveniently monitored in the stomach with a Tonomitor incorporated into a nasogastric tube, because changes induced in this organ by disturbances in DO2 reflect changes occurring in other parts of the gut. Preventative measures currently possible in routine clinical practice include maintaining an intramucosal pH at normal levels by optimizing DO2, preventing the release of splanchnic vasoconstrictors and the formation of cellular aggregates by the use of pulsatile perfusion during bypass, and minimizing oxygen requirements with cooling and muscle relaxation. The translocation of bacterial toxins and bacteria across injured mucosa may be minimized by gut lavage before surgery. Therapeutic measures for gut mucosal ischemia currently possible in routine clinical practice include, in addition to the preventative measures outlined above, the prevention of free radical-induced mucosal injury during resuscitation, parenteral antibiotics, the treatment of sepsis, and the resection of infarcted gut.
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PMID:Gut mucosal ischemia during cardiac surgery. 209 99


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