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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Differing antibiotic regimens can influence both survival and the inflammatory state in sepsis. We investigated whether the addition and/or type of antimicrobial agent could effect mortality in a murine model of Pseudomonas aeruginosa pneumonia-induced sepsis and if antibiotics altered systemic levels of cytokines. FVB/N mice were subjected to intratracheal injection of pathogenic bacteria and were given gentamicin, imipenem, or 0.9% NaCl 2 h after surgery, which continued every 12 h for a total of six doses. ⋯ Significant alterations in the proinflammatory cytokines TNF-alpha and IL-6 were present at all time points except 3 h between mice treated with antibiotics and sham controls. In contrast, statistically significant differences in the anti-inflammatory cytokine IL-10 were present between the groups only at 6 h, and levels of IL-12 were similar at all time points. These results indicate that both gentamicin and imipenem increase survival at least 10-fold in a model of pneumonia-induced monomicrobial sepsis, and this is predominantly associated with a down-regulation of proinflammatory cytokines.
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Comparative Study
Relationships of circulating nitrite/nitrate levels to severity and multiple organ dysfunction syndrome in systemic inflammatory response syndrome.
Excessive nitric oxide (NO) production has been implicated to be responsible for the development of septic shock. To determine whether plasma nitrite/nitrate (NOx) levels are related to the severity of systemic inflammatory response syndrome (SIRS) and the degree of multiple organ dysfunction, we studied plasma NOx levels in 70 patients with SIRS consisting of noninfectious SIRS (n = 32), sepsis (n = 23), and septic shock (n = 15). Infection is a microbial phenomenon characterized by an inflammatory response to the presence of microorganism. ⋯ Plasma NOx levels were positively correlated with Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III score (r = 0.414, P < 0.01) and sequential organ failure assessment (SOFA) score (r = 0.433, P < 0.01). Plasma NOx levels in patients with sepsis (51.0 +/- 38.5 microM/L) and septic shock (94.5 +/- 53.7 microM/L) were significantly (P < 0.01) higher than those in patients with noninfectious SIRS (25.8 +/- 16.9 microM/L) and healthy subjects (29.6 +/- 8.9 microM/L). Our study shows that plasma NOx levels are increased in patients with infectious, but not noninfectious SIRS, which increase as the severity of SIRS and the development of multiple organ dysfunction syndrome, suggesting its possible pathogenic role in SIRS.
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We tested the hypothesis in a rat model that body cooling suppresses circulatory shock and cerebral ischemia in heatstroke. Animals under urethane anesthesia were exposed to water blanket temperature (Tblanket) of 42 degrees C until mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the hippocampus began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 26 degrees C. ⋯ Cooling immediately after the onset of heatstroke reduced the heatstroke-induced circulatory shock, cerebral ischemia, neuronal damage, and surge of tissue ischemia and damage markers in the hippocampus, and resulted in prolongation of survival time. Delaying the onset of cooling reduced the therapeutic efficiency. The results suggest that body cooling attenuates circulatory shock and cerebral ischemia insults in heatstroke.
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Acute mitral regurgitation (MR) is present in 10% of patients presenting with cardiogenic shock. To stabilize these patients, intra-aortic balloon pumping (IABP) is recommended, but the mechanism of IABP support in these patients is unknown. This animal study was designed to describe the hemodynamic effect of intra-aortic balloon pumping during cardiogenic shock induced by acute MR. ⋯ Left ventricular function and mean coronary blood flow did not change, but diastolic coronary flow became more important as shown by the increase in diastolic fraction from 64% to 95%. (P = 0.028). Average MR dropped by 7.5% (P = 0.025). In conclusion, application of the IABP during acute MR lowers aortic impedance, resulting in less MR and more output toward the aorta without changing left ventricular function.
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Prior studies have shown that hemorrhage (Hem) can serve as a priming stimulus for acute lung injury (ALI) triggered by subsequent septic challenge (cecal ligation and puncture, CLP). Furthermore, we have reported that in vivo antibody neutralization of the chemokines, macrophage inflammatory chemokine-2 (MIP-2) and keratinocyte-derived chemokine (KC), immediately after Hem appears to differentially effect the onset of ALI. However, although we hypothesize that this is due to divergent effects of MIP-2 and KC on Hem-induced neutrophil (PMN) priming, this has not been tested. ⋯ The results show that donor PMN from Hem/IgG but not Sham-Hem mice produce increased PMN influx (increased MPO, increased % esterase+ cells in tissue) into the lung and local tissue inflammation (increased IL-6/MIP-2, decreased IL-10) in PMN-depleted CLP recipient mice, which was attenuated in mice receiving cells from Hem/anti-MIP-2 but not Hem/anti-KC treated donors. Interestingly, although Hem/anti-MIP-2 donor PMN produced comparable effects on blood IL-6/MIP-2 levels, they were ineffective in altering the change in plasma IL-10/KC levels induce by Hem. Taken together, these data demonstrate that Hem-induced priming of PMN not only mediates ALI in the mouse, but also that this process is differentially effected by MIP2 and KC, despite the fact that both signal through CXCR2.