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

We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility. Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures. The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP. Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision. All rats were killed 24 h after surgery. Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha). Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group. In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied. Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular reactivity in sepsis: importance of controls and role of nitric oxide. 788 60

Among the important pathophysiologic alterations in the brain in bacterial meningitis are abnormalities of cerebral circulation and metabolism; however, the precise mechanisms by which these disturbances occur are not completely delineated. It has been recently recognized that cytokines are produced by tissues in the central nervous system in meningitis and play a critical role in the host inflammatory response. Because these mediators are involved in circulatory and metabolic disturbances in other tissues in sepsis, we investigated the role of tumor necrosis factor-alpha in the central nervous system in a rabbit model. We found that injection of recombinant human TNF into the cisterna magna in the rabbit led to an acute reduction in cerebral oxygen uptake and a more prolonged reduction in cerebral blood flow. This was accompanied by an increase in intracranial pressure and an increase in cerebrospinal fluid lactate. Reduction in oxygen uptake and increases in intracranial pressure and CSF lactate were blocked by pretreatment with L-NAME, an inhibitor of nitric oxide synthase. Reduction in cerebral blood flow was not affected by L-NAME treatment and was due to increased cerebrovascular resistance and reduced oxygen demand. These results suggest that TNF may be a critical mediator of changes in cerebral circulation and metabolism and that some of these changes occur via the nitric oxide pathway.
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PMID:Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. 788 56

Accumulation and stimulation of PMN-leukocytes, enhanced prostaglandin metabolism and tissue hypoxia lead to high concentrations of oxygen radicals and their metabolites in septic shock. Synchroneously, excessive high concentrations of nitric oxide are found, most likely due to the stimulation of its inducible synthetase. Oxygen radicals seem to be attributable for the irreversible tissue damage leading to multiple organ failure in sepsis. High concentrations of nitric oxide induce the typical macro- and microcirculatory derangements normally seen in sepsis. Both mediators are present in the early phase of sepsis and seem to influence the course of disease. Therapeutic interventions such as scavenger therapy or inhibition of the inducible NO-synthetase are promising. The results of the first clinical therapeutic studies, however, were not always conclusive. It is still unclear which scavenger and which inhibitor should be given when and in which dosage in order to improve the outcome of sepsis and septic shock. Furthermore, it remains unclear to which extend oxygen radicals and nitric oxide react with each other, thus possibly potentiating their effects. The open questions still warrant further research and may lead to new therapeutic options improving the morbidity and mortality of this severe disease.
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PMID:[Oxygen radicals and nitrogen monoxide in sepsis]. 788 85

The endothelium is critically involved in the regulation of vascular function through its barrier role, via interaction with circulating cells such as platelets, which then release vasoactive or growth regulating agents, through production of substances which may modulate vascular tone and smooth muscle cell growth and also exert anti-thrombotic effects. The release of serotonin, adenosine diphosphate (ADP), or growth factors from platelets adhering to damaged endothelium, the release of endothelium-derived relaxing or contracting factors (nitric oxide, prostanoids, endothelin), the production of growth factors, all of which exert their effects in paracrine or even autocrine fashion, are some of the mechanisms whereby the endothelium influences vascular tone and growth and platelet aggregation. In different conditions such as hypertension, atherosclerosis, diabetes, heart failure, ischemic heart disease, sepsis, and shock, dysfunction of the endothelium plays an important pathophysiological role through reduction or enhancement of the release of these different products with significant hemodynamic and trophic effects. Therapeutic interventions targeting the endothelium hold promise in the treatment and prevention of some cardiovascular diseases and their complications.
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PMID:The endothelium and control of blood vessel function in health and disease. 789 24

Nitric oxide and atrial natriuretic peptides are the main activators of guanylyl cyclases, which transform GTP into cyclic GMP and thereby contribute to the decrease of vascular tone. To investigate the increase, if any, of plasma cyclic GMP concentrations in human patients with hyperdynamic circulation resulting from acute liver failure and to ascertain whether guanylyl cyclase activation is involved in the decline of systemic vascular resistance that occurs in this pathophysiological condition, we simultaneously recorded hemodynamic data and cyclic GMP levels in patients with fulminant liver failure before and after liver transplantation and in normokinetic patients undergoing abdominal nonseptic surgery. We also compared these data with those recorded in patients with hyperkinetic shock resulting from gram-negative sepsis or nitric oxide-independent vasomotor agent (carbamate) over-dose. In all these patients we simultaneously studied kidney function, platelet counts and atrial natriuretic peptides. Patients with fulminant liver failure had higher cyclic GMP concentrations than did control patients undergoing abdominal surgery (11.02 +/- 1.55 pmol.ml-1 vs. 1.77 +/- 0.18 pmol.ml-1, p < 0.001). At similar heart-loading conditions these concentrations were lower than those in gram-negative septic shock (18.2 +/- 1.35 pmol.ml-1, p < 0.05) but higher than those in carbamate-induced shock (3.6 +/- 0.7 pmol.ml-1, p < 0.01). In addition, cyclic GMP concentrations significantly decreased from the fulminant liver failure period to the posttransplantation period, although atrial natriuretic peptide levels did not change significantly and kidney function worsened.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo evidence of enhanced guanylyl cyclase activation during the hyperdynamic circulation of acute liver failure. 790 53

Nitric oxide synthesized by a constitutive enzyme is a widespread mediator of cell-cell and intracellular communication. This mediator provides a continuous vasodilator influence in the cardiovascular system, modifies the function of circulating cells, and acts as a neurotransmitter. After exposure to bacterial endotoxin or certain cytokines, expression of a second, inducible nitric oxide synthase occurs in a wide variety of tissues. This enzyme produces large amounts of nitric oxide for long periods and has been implicated in pathophysiologic changes seen in sepsis. In some cells, including macrophages, the nitric oxide synthesized by the inducible enzyme is toxic and appears to be an important mediator in host defense. Studies in animals and in vitro have demonstrated that nitric oxide released from inducible nitric oxide synthase in other tissues may cause profound vasodilation, damage to host cells, and cardiac dysfunction. The hypotension of endotoxin- or cytokine-induced shock can be reversed by inhibitors of nitric oxide synthase and these agents may provide a novel therapeutic approach to the treatment of severe septic shock. Preliminary studies in humans suggest that inhibition of nitric oxide synthase improves BP and stabilizes hemodynamics; effects on mortality rates remain to be determined.
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PMID:Role of endogenous nitric oxide in septic shock. 792 96

In this review, the second of a two part series, the analytic techniques introduced in the first part are applied to a broad range of pulmonary pathophysiologic conditions. The contributions of hypoxic pulmonary vasoconstriction to both homeostasis and pathophysiology are quantitated for atelectasis, pneumonia, sepsis, pulmonary embolism, chronic obstructive pulmonary disease and adult respiratory distress syndrome. For each disease state the influence of principle variables, including inspired oxygen concentration, cardiac output and severity of pathology are explored and the actions of selected drugs including inhaled nitric oxide and infused vasodilators are illustrated. It is concluded that hypoxic pulmonary vasoconstriction is often a critical determinant of hypoxemia and/or pulmonary hypertension. Furthermore this analysis demonstrates the value of computer simulation to reveal which of the many variables are most responsible for pathophysiologic results.
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PMID:Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 2. Pathophysiology. 793 36

We wanted to determine whether the production of endogenous nitric oxide (NO) is affected by cigarette smoking and various pathological conditions. Endogenously produced NO was measured by chemiluminescence in the exhaled air of 81 healthy volunteers (21 nonsmoking females (NSF), 12 smoking females (SF), 24 nonsmoking males (NSM) and 24 smoking males (SM)) and 38 patients (10 with hypertension, 10 intra- and 10 postoperative, 5 with renal failure and 3 with sepsis) entered the protocol. Subjects inspired from a NO-free air supply, which was also used to calibrate the NO-analyser. Endogenous NO production of volunteers was 18 +/- 8 per billion (ppb) depending on smoking habits. In exhaled air of NSF, NO concentration was 21 +/- 7 ppb, in SF 16 +/- 6 ppb, in NSM 19 +/- 8 ppb and in SM 15 +/- 6 ppb. Differences between smokers and nonsmokers were significant. Increased diastolic blood pressure was noted in SM compared to NSM (86 +/- 7 versus 78 +/- 7 mmHg). Patients with documented and treated hypertension (systolic and diastolic blood pressure: 141 +/- 18 and 82 +/- 9 mmHg) exhaled 13.7 +/- 5.3 ppb NO; hypertensive males 10 +/- 2 ppb NO and females 17 +/- 5 ppb NO. In patients with renal failure NO concentration in exhaled air was 20.2 +/- 6.8 ppb before and 19.8 +/- 6.4 ppb one hour after the onset of dialysis. In patients undergoing major surgery NO concentration was 5.6 +/- 2.5 ppb intra- and 10.3 +/- 3.5 ppb postoperatively. In three mechanically ventilated patients with documented septic syndrome, exhaled NO was 29.3 +/- 24 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced endogenous nitric oxide in the exhaled air of smokers and hypertensives. 801 3

Nitric oxide (NO) is an important mediator of the hemodynamic response to sepsis; however, its visceral microcirculatory effects are largely unknown. To determine the role of NO in renal microvascular responses to bacteremia, rat hydronephrotic kidneys with intact neurovascular supplies were exteriorized into a tissue bath. Videomicroscopy was used to measure vessel diameters (interlobular artery, ILA; afferent arteriole, AFF; efferent arteriole, EFF) and optical Doppler velocimetry was used to quantitate ILA flow. In controls, topical L-arginine (L-Arg; 10(-4) M), the NO synthase (NO-S) substrate, resulted in mild pre- and postglomerular dilation and increased flow. Inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME: 10(-4) M) caused preglomerular constriction (ILA = -22%; AFF = -20% from baseline) and reduced ILA flow by 39%, while postglomerular diameters (EFF) were unchanged. Bacteremic rats had similar alterations (ILA = -22%; AFF = -20%; flow = -56%). Topical L-NAME in bacteremic rats resulted in further constriction (ILA = -38%; AFF = -37%), decreased ILA flow (-75%) and constricted EFF (-30%). L-Arg ameliorated constriction (ILA = -11%; AFF = -7%) and flow (-34%) during bacteremia. We conclude that: (1) NO is important in basal preglomerular tone; (2) Escherichia coli causes selective preglomerular constriction and hypoperfusion; (3) maintenance of EFF tone during bacteremia is NO dependent; and (4) different pre- and postglomerular NO mechanisms exist during basal and bacteremic states. These data indicate that NO is an important mediator of renal microvascular responses to sepsis.
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PMID:Renal microvascular responses to sepsis are dependent on nitric oxide. 801 6

Recent studies have identified the induction of nitric oxide (NO) synthesis in many cell types as part of the host response to sepsis and inflammation. Induced NO can have a variety of effects which may be detrimental or beneficial during sepsis or inflammation, depending on amount, duration, and anatomic site of synthesis. As arginine is the only physiological nitrogen donor for NO synthesis, metabolism of this amino acid may play an important role in regulation of NO synthesis during sepsis. This review will discuss the roles NO plays in sepsis and the potential impact of arginine metabolism on NO synthesis.
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PMID:New insights into the regulation of inducible nitric oxide synthesis. 802 11


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