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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The pathogenesis of stroke involves inflammation, apoptosis, and excitotoxicity, which is mediated in part by neuronal NO synthase (nNOS) activation. Ghrelin, an endogenous 28-amino acid peptide, is shown to exert antiapoptotic and anti-inflammatory properties. However, the effect of ghrelin in permanent focal cerebral ischemia and the role of the vagus nerve in its action remain unknown. ⋯ Human ghrelin treatment also improved 7-day survival and significantly decreased neurological deficit over the entire 7 days after MCAO in vagus nerve-intact rats compared with vehicle. Prior vagotomy, however, blunted human ghrelin's neuroprotective effects on neurological deficit, infarct size, TNF-α, neutrophil trafficking, nitrotyrosine, and apoptosis. Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway.
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Leukotrienes are proinflammatory lipid mediators, derived from arachidonic acid via 5-lipoxygenase (5-LO). Leukotriene B4 (LTB4) is an effective polymorphonuclear neutrophil (PMN) chemoattractant, as well as being a major product of PMN priming. Leukotriene B4 is rapidly metabolized into products that are thought to be inactive, and little is known about the effects of LTB4 on the pulmonary endothelium. ⋯ Silencing of BLT2 abrogated HMVEC activation, and blockade of BLT1 inhibited the observed PMN priming activity. We conclude that LTB4 and its ω-oxidation and nonenzymatic metabolites prime PMNs over a range of concentrations and activate HMVECs. These data have expanded the repertoire of causative agents in acute lung injury and postinjury multiple organ failure.
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Randomized Controlled Trial
A prospective randomized trial using blood volume analysis in addition to pulmonary artery catheter, compared with pulmonary artery catheter alone, to guide shock resuscitation in critically ill surgical patients.
Measurement of blood volume (BV) may guide fluid and red blood cell management in critically ill patients when capillary leak from shock and fluid resuscitation makes assessment of intravascular volume difficult. This is a prospective randomized trial of critically ill surgical patients with septic shock, severe sepsis, severe respiratory failure, and/or cardiovascular collapse. The control group received fluid management based on pulmonary artery catheter parameters and red blood cell transfusions based on hematocrit values. ⋯ Blood volume analyses provided additional information to the clinicians resulting in a change in treatment in 44% of the time to patients randomized to the BV group. The mortality rates were significantly different between the two groups (8% for the BV group and 24% in the control group; P = 0.03). Blood volume measurements allowed the physicians to promptly treat physiologic disturbances in both red blood cell volume and plasma volume, resulting in improved survival.
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The systemic inflammatory response syndrome often accompanies critical illnesses and can be an important cause of morbidity and mortality. Marked abnormalities in cardiovascular function accompany acute illnesses manifested as sustained tachyarrhythmias, which are but one component of systemic dysregulation. The realization that cardiac pacemaker activity is under control of the autonomic nervous system has promoted the analysis of heart rate (HR) variation for assessing autonomic activities. ⋯ In the present study, changes in HR response to acute injury, phenotypically expressed as tachycardia, are simulated as a result of autonomic imbalance that reflects sympathetic activity excess and parasympathetic attenuation. The proposed model assesses both the anti-inflammatory and cardiovascular effects of antecedent stresses upon the systemic inflammatory manifestations of human endotoxemia as well as a series of nonlinear inflammatory relevant scenarios. Such a modeling approach provides a comprehensive conceptual framework linking inflammation and physiological complexity via a multiscale model that may advance the translational potential of systems modeling in clinical research.