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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Elderly humans are more vulnerable to trauma and hemorrhage than young and elderly men and respond with decreased defense of central blood volume during acute experimental hypovolemia induced by lower body negative pressure (LBNP). However, these defense mechanisms have not been evaluated in elderly women. The aim of this study was to determine the effectiveness of compensatory responses to defend central blood volume during experimental hypovolemia in elderly and young women. ⋯ Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ∼60% in elderly women (P < 0.001), and net capillary fluid absorption from surrounding tissues was reduced by ∼40% (P < 0.01, LBNP of 44 mmHg). Elderly women responded with less increase in heart rate but with equal forearm vascular resistance (%) response during LBNP. Furthermore, the compensatory capacitance response was both slower and substantially decreased, and net capillary fluid absorption considerably reduced, collectively indicating less efficiency to defend central blood volume in elderly than in young women.
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In clinical practice, prolonged occlusion of main arteries causes accumulation of metabolic waste and lactate. Reperfusion of blood flow is usually accompanied by circulatory shock. This study investigates the molecular mechanisms responsible for acidosis-induced hypotension and proposes therapeutic strategies for improving hemodynamic stability following ischemia-reperfusion acidosis. ⋯ Recording of electrocardiogram showed progressive development of bradyarrhythmia with ST-segment elevation in animals pretreated with PNU37883A before reperfusion. We demonstrate that acidosis-induced vasodilation is, in part, mediated by the activation of KATP channels through reduction of intracellular Ca in VSMCs. However, systemic antagonism of KATP channel significantly increases the overall mortality secondary to the development of cardiac dysrhythmia in animals with profound experimental metabolic acidosis, suggesting that activation of KATP channel is a protective response during reperfusion acidosis.
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Patients with crush injury often present systemic inflammatory response syndrome and fall into multiple organ failure. The mechanism by which the local tissue damage induces distant organ failure is still unclear. We focused on high-mobility group box 1 protein (HMGB1) as one of the damage-associated molecular pattern molecules that cause systemic inflammation in crush injury. ⋯ These results indicate that HMGB1 is released in response to damage immediately after crush injury and acts as a proinflammatory mediator. Administration of anti-HMGB1 antibody reduced inflammatory reactions and improved survival by blocking extracellular HMGB1. Thus, HMGB1 appears to be a therapeutic target, and anti-HMGB1 antibody may become a promising novel therapy against crush injury to prevent the progression to multiple organ failure.
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The management of severe traumatic brain injury (TBI) focuses on prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). Predicting which patients will develop these secondary insults is currently not possible. This study investigates the systemic manifestation of neuroinflammation and its role in helping to predict clinical deterioration following severe TBI. ⋯ Interleukin 8 and TNF-α demonstrate promise as candidate serum markers of impending ICH and CH. This suggests that we may be able to "predict" imminent events following TBI before clinical manifestations. Given the morbidity of ICH and CH, minimizing the effects of these secondary insults may have a significant impact on outcome and help guide decisions about timing of interventions.
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The plasma level of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been shown to be helpful in identifying critically ill patients with infection. However, it remains unknown whether it can be used to predict prognosis in patients with severe sepsis. This study investigated whether various inflammatory mediators, including sTREM-1, could be used as reliable markers to predict the prognosis of patients receiving early goal-directed therapy (EGDT). ⋯ The only sTREM-1 level remained significantly higher in nonsurvivors until death. On multivariate regression analysis, log(sTREM-1) (P = 0.028), central venous oxygen saturation (P = 0.022), and Simplified Acute Physiology Score II (P = 0.048) values at admission were independently significant. These results suggest that plasma sTREM-1 level at admission could be used as a marker to identify patients with a poor prognosis despite complete initial resuscitation in severe sepsis.