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

The central hemodynamic responses were studied in experimental sepsis in cats, following various routes of infusion of live E. coli bacteria. The aortic blood flow (ABF) was electromagnetically recorded. The pulmonary artery was cannulate for pressure recording. Platelet and white blood cell concentrations, PO2, PCO2, pH and oxygen saturation were measured at intervals. I.v. infusion of bacteria induced initially decreased ABF, systemic hypotension, pulmonary hypertension. Portal infusion evoked, on the other hand, increased ABF, but induced no significant change in systemic or pulmonary arterial blood pressures. Aortal infusion induced responses in between. The initial hemodynamic changes were followed by relative normalization after 5-10 min. Then, in all series, a progressive fall in ABF and systemic blood pressure were noticed. Within 5 min following bacterial infusion the platelet and white blood cell concentrations fell to 65 and 50%, respectively. In all series a moderate metabolic acidosis developed. Thus, the initial hemodynamic response following infusion of live E. coli was dependent on the route of infusion; intraportal infusion induced initially a more hyperdynamic state. The different initial central hemodynamic responses did not influence the subsequent development of a hypotensive shock state.
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PMID:Central hemodynamic responses to venous, aortal or portal infusion of live E. coli bacteria in the cat. 704 28

The validity of animal models of human sepsis has been questioned. We describe a patient who experienced a short episode of endotoxemia (? bacteremia) with resultant pulmonary hypertension, pulmonary edema from increased alveolar capillary membrane permeability, hypoxemia, hypotension, and relative leukopenia, which mimics the pathophysiologic changes noted following infusion of Pseudomonas bacteria into awake sheep. The similarity of abnormalities and their resolution suggests that Pseudomonas infusion in sheep is a valid experimental model of human septic shock.
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PMID:Pathophysiologic alterations in endotoxemia. Similarities to an animal model. 738 73

Pulmonary hypertension gives an indication of poor prognosis in adult respiratory distress syndrome (ARDS) complicating sepsis. In this study, we examined the role of the platelet and the vasoactive amine, serontonin, in pulmonary hypertension accompanying septic ARDS. The lack of any significant difference in platelet number (delta + 3.9 +/- 8.4, X 10(3)/mm3) or serum serotonin (delta - 0.03 +/- 0.06 nm/mm3) across the pulmonary vascular bed (pulmonary artery minus pulmonary vein), would suggest that platelet sequestration and/or release of serotonin is not a major factor in septic ARDS. However, we did note a direct positive relationship between serum serotonin (Ss) and the pulmonary artery diastolic minus pulmonary capillary wedge pressure (PAd-PCWP) gradient (r = 0.64, p < 0.01) implying that serum serotonin may be related to pulmonary hypertension in septic ARDS.
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PMID:Serotonin and pulmonary hypertension in human septic ARDS. 741 23

Reactive oxygen metabolites are believed to be important mediators of sepsis- or lipopolysaccharide (LPS)-induced adult respiratory distress syndrome. EUK-8 is a novel, synthetic, low-molecular-weight salen-manganese complex that exhibits both superoxide dismutase and catalase activities in vitro. We hypothesized that treatment with EUK-8 would ameliorate pulmonary dysfunction in a porcine model of LPS-induced adult respiratory distress syndrome. At T = -18 h, pigs received an intravenous priming dose of LPS (20 micrograms/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 5); 2) LPS (250 micrograms/kg from T = 0 to 60 min, n = 6); 3) LPS and a low dose of EUK-8 (10-mg/kg bolus at T = -15 min and 1 mg/kg.h from T = 0 to 240 min, n = 6) or 4) LPS and a higher dose of EUK-8 (10-mg/kg bolus and 3 mg/kg.h, n = 6). Treatment with EUK-8, particularly at the higher dose, significantly attenuated many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance and pulmonary edema. LPS caused an increase in lung tissue malondialdehyde content that was abrogated in both EUK-8-treated groups. EUK-8 treatment had no effect on circulating plasma levels of tumor necrosis factor-alpha, thromboxane B2 or 6-keto-prostaglandin F1 alpha. We conclude that EUK-8 prevents many of the manifestations of LPS-induced adult respiratory distress syndrome in pigs by detoxifying reactive oxygen metabolites without affecting the release of other important proinflammatory mediators.
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PMID:EUK-8, a synthetic superoxide dismutase and catalase mimetic, ameliorates acute lung injury in endotoxemic swine. 747 69

Nitric oxide (NO), an important vasodilatory modulator of systemic and pulmonary vascular tone, is synthesized from L-arginine by the enzyme NO synthase in vascular endothelial and smooth muscle cells. L-Arginine analogs, such as N omega-nitro-L-arginine methyl ester (L-NAME), are competitive antagonists of NO synthase and inhibit NO synthesis. Group B streptococcus (GBS) causes pulmonary hypertension, hypoxemia, lung vascular injury, and reduced cardiac output in both human newborns and neonatal piglets. Lung vascular injury associated with prolonged GBS infusion in piglets may attenuate NO production and thus promote severe pulmonary hypertension. We studied the effect of the NOS inhibitor, L-NAME and the precursor of NO, L-arginine, on pulmonary and systemic hemodynamics during late-phase GBS sepsis in the piglet model. Neonatal piglets were anesthetized, ventilated with room air, and randomized to receive a continuous infusion of saline (n = 5) or GBS (n = 5) for 4 h. After 3 h of infusion, both groups received a bolus of L-NAME (3 mg/kg). Hemodynamic and gas exchange indices were measured at baseline, 30 min, and 3 h of infusion, and 30 min and 1 h after L-NAME treatment. L-NAME treatment caused 1) significant increases in mean pulmonary arterial pressure, pulmonary vascular resistance, mean systemic arterial pressure, and systemic vascular resistance for both groups; 2) a similar percentage of increase in pulmonary vascular resistance for the two groups; 3) greater reduction in cardiac output and SV in the GBS compared with the control group; and 4) no significant alterations in arterial partial pressure of oxygen or the difference between alveolar and arterial partial pressure of oxygen for either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nitric oxide synthase inhibition during group B streptococcal sepsis in neonatal piglets. 753 3

A 2-month-old girl presented with enlarged head girth, generalized petechiae, anemia, coagulopathy and hepatosplenomegaly. Imaging studies showed a huge, dumbbell-shaped intracranial hemangioma located between the falx, and involving the supra- and infra-tentorium, extending through the posterior fontanel to involve the subgaleal area. A urine culture grew cytomegalovirus. Severe thrombocytopenia was refractory to a massive platelet transfusion, intravenous immunoglobulin and corticosteroid therapy. Hypertension, pulmonary hemorrhage and sepsis complicated the course. After establishing a diagnosis of Kasabach-Merritt syndrome, subcutaneous injections of alpha-interferon were given with an initial dose of 1 x 10(6) IU/m2 followed by 3 x 10(6) IU/m2 per day for 12.5 mo. Her platelet count rose gradually and became stable after 1.5 mo of interferon treatment. The intracranial hemangioma regressed remarkably and the hepatosplenomegaly was also resolved. The infant showed good growth and development, without obvious side-effects during the 23-month follow-up period. The treatment with recombinant alpha-interferon appeared to be effective in reversing thrombocytopenia associated with the patient's massive intracranial hemangioma.
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PMID:Recombinant alpha-interferon treatment of intracranial hemangioma and Kasabach-Merritt syndrome in an infant with cytomegalovirus. 761 60

The early phase of endotoxin-induced acute hemodynamic disturbances and hypoxemia is mediated by various factors, including eicosanoids and tumor necrosis factor-alpha (TNF alpha). Thromboxane A2 is the major mediator of the early pulmonary hypertension associated with endotoxemia, but the mechanisms underlying the prolonged hemodynamic disturbances observed in ongoing endotoxemia are not well understood. The authors used a chronically instrumental young piglet model to determine the roles of several eicosanoids and of TNF alpha in the prolonged endotoxin-induced pulmonary hypertension and other cardiovascular derangements. Animals were given 40 micrograms/kg endotoxin intravenously per hour for 30 minutes, followed by 20 micrograms/kg per hour. In all animals, persistent pulmonary hypertension, lowered cardiac output, any hypoxemia developed during endotoxin infusion. After 3 hours of endotoxin infusion, randomly ordered infusions of 1 mg/kg dazmegrel (a thromboxane A2 synthesis inhibitor), 5mg/kg nordihydroguaiaretic acid (a 5-lipoxygenase inhibitor), and 20 mg/kg pentoxifylline (A TNF alpha inhibitor) were given intravenously at 30-to-60-minute intervals. Dazmegrel and pentoxifylline lowered pulmonary arterial pressure and resistance and raised arterial oxygen tension. Cardiac output increased significantly after pentoxifylline. These hemodynamic effects persisted for 30-60 minutes, despite continued endotoxin infusion. The elevated plasma concentrations of thromboxane B2 and TNF alpha returned toward preendotoxin baseline values after dazmegrel and pentoxifylline treatment, respectively. No beneficial effects were noted after administration of nordihydroguaiaretic acid. Based on these results, both thromboxane A2 and TNF alpha, but not 5-lipoxygenase products, play active roles in prolonged endotoxin-induced pulmonary hypertension and hypoxemia in young piglets. Combined thromboxane A2 and TNF alpha blockade may be clinically useful in treatment of advanced sepsis in neonates.
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PMID:Delayed thromboxane or tumor necrosis factor-alpha, but not leukotriene inhibition, attenuates prolonged pulmonary hypertension in endotoxemia. 766 5

Many questions remain unanswered (and probably many more remain unasked) about neonatal sepsis. In addition, many mediators of inflammation have been implicated in neonatal sepsis at one time or another. The goal of this article is to put together what the authors view as some of the more important outstanding questions with what is known about some of the more important mediators. We address four questions specifically: (1) Why is neonatal sepsis different from all other (adult) sepsis? (2) 41Is control of pulmonary hypertension the white whale or red herring in neonatal septic shock? (3) Is sepsis more like dominoes or like 52 pick-up? and (4) Is disruption of QO2/VO2 coupling a legitimate clinical concern or a laboratory anomaly?
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PMID:Inflammatory mediators and neonatal sepsis. Rarely has so little been known by so many about so much. 767 49

Sepsis has been shown to cause right ventricular (RV) dysfunction, which may be related to pulmonary hypertension and increased RV afterload. This study evaluates the effects of inhaled nitric oxide (NO), a selective pulmonary vasodilator, on RV function in a porcine model of endotoxemia. After an infusion of Escherichia coli lipopolysaccharide (LPS; 200 micrograms/kg), animals were resuscitated with saline (1 mL/kg/min) and observed for 3 hours while being mechanically ventilated (Fio2 = 0.6, tidal volume = 12 mL/kg, and peak end-expiratory pressure = 5 cm H2O). The LPS group (n = 5) received no additional treatment. The NO group (n = 5) received inhaled NO (40 ppm) for the last 2 hours. The control group (n = 5) received only saline without LPS. Hemodynamic data and blood gases were collected hourly for 3 hours. LPS resulted in pulmonary hypertension and RV dysfunction as indexed by a decreased RV ejection fraction and increased RV end-diastolic volume. Inhaled NO significantly decreased pulmonary hypertension and significantly increased RV ejection fraction and oxygen delivery without adverse effects. In conclusion, inhaled NO significantly improved pulmonary hypertension and RV dysfunction in a porcine model of endotoxemia and should be a useful therapeutic modality in selected septic patients.
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PMID:Effects of inhaled nitric oxide on right ventricular function in endotoxin shock. 767 83

This limited discussion focuses on the apparent magnitude of the importance of NO-related mechanisms in the maintenance of blood flow to a number of tissue beds, the exaggerated effects in cirrhotics, its effects on platelets and immune modulation, and the potential for manipulation with agonists and antagonists. The possibility of pharmacologic control of this system may play a significant role in the management of patients with liver disease, whether for the treatment of the hypotension associated with low SVR, or endotoxemia/sepsis, or the pulmonary hypertension seen in approximately 1.6% of liver transplant candidates. This is a complex, heavily interrelated system, and the veracity of these various experimental claims for NO needs to be thoroughly evaluated for clinical relevance.
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PMID:Nitric oxide: an important bioregulator. 768 61


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