Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Calcium plays an important role in determining vascular smooth muscle tone. Norepinephrine (NE)-induced vascular contraction contains two components: 1) Ca2+ release from the sarcoplasmic reticulum as the fast phase and 2) Ca2+ influx via a voltage-dependent calcium channel as the slow phase. This study used functional isometric tension recording to evaluate mediators contributing to abnormal NE-induced Ca2+ handling and reactivity in isolated thoracic aortas from septic rats. ⋯ Inhibition by 2-aminoethoxy-diphenyl borane, ryanodine, and cyclopiazonic acid of the NE-induced contraction in Ca2+-free solution was greater in the aorta from sepsis rats and inhibitions of cyclopiazonic acid and ryanodine, but not of 2-aminoethoxy-diphenyl borane, were attenuated by NOS inhibitor N[omega]-nitro-l-arginine methyl ester. In addition, the attenuation of NE-induced contraction by nifedipine in the aorta was also greater in the CLP group. Our results suggest that abnormal NE-induced Ca2+ handling associated with vascular hyporeactivity in the CLP-induced sepsis is caused by a major decrease in sarcoplasmic reticulum function and a minor impairment of voltage-dependent Ca2+ channels on membrane to Ca2+ handling, at least, in the aorta, and this could be attributed to an overproduction of NO in sepsis.
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Although patients with obstructive jaundice are susceptible to bacterial infections and cancers, the mechanisms remain to be elucidated. In the present study, liver mononuclear cells (MNCs) of bile duct-ligated (BDL) mice were immunologically assessed. Liver natural killer T cells were greatly decreased within 24 h after BDL. ⋯ IFN-gamma production by liver MNC from normal mice stimulated with LPS in vitro was inhibited by the addition of bile acids, whereas, conversely, the production of IL-12 and IL-18 increased. In conclusion, liver natural killer T cells were diminished in BDL mice, and the function of liver MNC (IFN-gamma production) was also impaired presumably due to increased bile acids. This may partly explain the increased susceptibility of BDL mice to bacterial infections and tumor metastasis.
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Randomized Controlled Trial
Efficacy and safety of dopamine versus norepinephrine in the management of septic shock.
The optimum septic shock vasopressor support strategy is currently debated. This study was performed to evaluate the efficacy and safety of norepinephrine (NE) and dopamine (DA) as the initial vasopressor in septic shock patients who were managed with a specific treatment protocol. A prospective, randomized, open-label, clinical trial was used in a medical intensive care unit comparing DA with NE as the initial vasopressor in fluid-resuscitated 252 adult patients with septic shock. ⋯ In this protocol-directed vasopressor support strategy for septic shock, DA and NE were equally effective as initial agents as judged by 28-day mortality rates. However, there were significantly more cardiac arrhythmias with DA treatment. Patients receiving DA should be monitored for the development of cardiac arrhythmias (NCT00604019).
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Increased catecholamine (CA) levels after severe burn are associated with stress, inflammation, hypermetabolism, and impaired immune function. The CA secretion profiles in burned patients are not well described. Mechanisms, duration, and extent of CA surge are unknown. ⋯ There were differences over time in survivors versus nonsurvivors, with CA levels significantly higher in nonsurvivors at two time points. Inflammatory cytokines show a similar profile during the study period. Our study gives clinicians a useful insight into the extent and magnitude of CA elevation to better design treatment strategies.