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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Our previous studies have shown that acute alcohol intoxication (AAI) decreases blood pressure, exacerbates hypotension after hemorrhagic shock, impairs the pressor response to fluid resuscitation, and blunts neuroendocrine activation. We hypothesized that impaired hemodynamic compensation during and after hemorrhagic shock in the acute alcohol-intoxicated host is the result of blunted neuroendocrine activation or, alternatively, of an impaired vascular responsiveness to vasoactive agents. The aim of this study was to examine the effects of AAI, AAI and hemorrhagic shock, and AAI and hemorrhagic shock and resuscitation on reactivity of isolated blood vessel rings to phenylephrine and acetylcholine. ⋯ Acute alcohol intoxication did not produce significant alterations in either pressor or dilator responses in aortic or mesenteric rings. These findings suggest that impaired hemodynamic counterregulation during hemorrhagic shock in AAI is not due to decreased vasopressor responsiveness. However, our results suggest a role for accentuated vasodilatory responses that may be central in progression to decompensatory shock.
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Oxidative stress during reperfusion of ischemia is associated with a phenotypic change in circulating monocytes from CD14++CD16- to a proinflammatory CD14+CD16+ subpopulation resulting in altered immunity and development of organ failure. However, the mechanism responsible remains unknown. We hypothesize that this phenotypic change, modeled by hydrogen peroxide exposure in vitro, is due to oxidative-induced intracellular calcium flux and distinct cytoskeletal and lipid raft changes. ⋯ This increase in CD16 expression was associated with a 27% increase in intracellular TNF-alpha, an alteration in actin polymerization, and the formation of raft macrodomains. These changes induced by H2O2 were inhibited by inhibition of actin polymerization (cytochalasin D and lactrunculin A) and intracellular calcium flux [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]. This study provides the first evidence that phenotypic alterations induced by oxidative stress during reperfusion may occur as a result of changes in cytoskeletal architecture due to calcium flux that result in lipid raft alterations rather than solely from demargination and/or production of bone marrow-derived CD16+ monocytes.
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Heart rate complexity (HRC) is an emerging "new vital sign" for critically ill and injured patients. Traditionally, 800-beat data sets have been used to calculate HRC variables, thus limiting their practical use in an emergency. We sought to investigate whether data set reductions diminish the use of HRC to predict mortality in prehospital trauma patients. ⋯ This finding was confirmed for data sets as short as 100 beats by computationally different metrics. SampEn, SOD, and complex demodulation were relatively unaffected by data set reduction. These metrics may be useful for rapid identification of trauma patients with potentially lethal injuries using short EKG data sets.
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In severely injured and hypoperfused trauma patients, endogenous acute coagulopathy (EAC) is associated with an increased morbidity and mortality. Recent human data correlate this coagulopathy with activation of the protein C pathway. To examine the mechanistic role of protein C in the development of EAC, we used a mouse model of trauma and hemorrhagic shock, characterized by the combination of tissue injury and severe metabolic acidosis. ⋯ However, complete blockade of both the anticoagulant and cytoprotective functions of aPC caused 100% mortality within 45 min of shock, with histopathology evidence of pulmonary thrombosis and perivascular hemorrhage. These results indicate that our unique mouse model of T/H shock mimics our previous observations in trauma patients and demonstrates that EAC is mediated by the activation of the protein C pathway. In addition, the cytoprotective effect of protein C activation seems to be necessary for survival of the initial shock injury.
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Methicillin-resistant Staphylococcus aureus (MRSA) infections with severe outcomes such as sepsis and septic shock are progressively increasing in both the community and in hospital settings. We hypothesized that overexpression of reactive nitrogen and oxygen species and vascular endothelial growth factor (VEGF) play a pivotal role in cardiovascular collapse associated with vascular hyperpermeability in MRSA sepsis. Twelve sheep were surgically prepared and randomized into a control (noninjured; n = 6) and a sepsis (injured; n = 6) group. ⋯ Cardiovascular variables in the control group remained stable, whereas the MRSA sepsis group developed a hypotensive and hyperdynamic circulatory shock state beginning at 6 h associated with significantly increased vascular permeability evidenced by increased prefemoral lymph flow starting at 12 h and permeability index from 12 to 18 h, higher fluid accumulation from 12 to 24 h, and significantly decreased plasma protein concentration and oncotic pressure beginning at 6 h compared with control animals. Myocardial 3-nitrotyrosine (3-NT) protein, poly (adenosine diphosphate-ribose), and VEGF mRNA expressions measured after the 24-h experiment were significantly increased in the injured animals as well. These results evidence that excessive production of reactive radicals and VEGF may play a major role in cardiovascular collapse and vascular hyperpermeability in MRSA sepsis.