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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Hemorrhagic shock and splanchnic arterial occlusion (SAO) followed by reperfusion are associated with high mortality. However, rapid cardiovascular failure and death may also occur before reperfusion in hemorrhagic shock and SAO. We show in a rat SAO model that, upon gut ischemia, mean arterial blood pressure transiently elevates and then drops fatally in one of two time courses: (i) gradually over ∼1 to 3 h or (ii) rapidly (often by >80 mmHg) over a period of 1 to 6 min. ⋯ Total subdiaphragmatic vagotomy or glycopyrrolate treatment significantly reduced the incidence to 0% (P < 0.008), although slow fatal pressure drops still occurred. ANGD did not prevent FFPDs, but delayed onset of slow fatal pressure drops (P < 0.013). These results suggest that gut ischemia can cause sudden death via an autonomic nervous system mechanism and that SAO with Glucose and xylazine may serve as a useful model for the study of neurogenic shock or autonomic dysregulation associated with sudden death.
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We have demonstrated that 100% oxygen inhalation is beneficial to zymosan-induced generalized inflammation, and reactive oxygen species may be involved in the protection of oxygen treatment. Other investigators suggest that reactive oxygen species may modulate the sympathetic nervous system activity and β2-adrenergic receptor (β2AR)-mediated pathway. Moreover, studies have demonstrated that β2AR agonists are beneficial to sepsis. ⋯ We also showed that zymosan induced the increase in serum 3'-5'-cyclic adenosine monophosphate (cAMP) and the decrease in tissue cAMP. However, oxygen treatment increased the cAMP levels in both serum and tissue, which were partly abolished by pretreatment with butoxamine. Thus, 100% oxygen inhalation may protect against zymosan-induced generalized inflammation in mice partly through activation of β2AR pathway and subsequently enhance cAMP levels in both serum and tissue.
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In low-flow states, such as circulatory shock, both fluids and catecholamines are often coadministered. We have previously found that adrenergic agents alter volume expansion after a fluid bolus. The present study tested the volume expansion properties of dobutamine and norepinephrine in sheep treated with (series 1) and without (series 2) a fluid bolus. ⋯ Dobutamine and norepinephrine increased ΔPV over time, 5.1 ± 0.5 and 4.0 ± 0.5 mL x kg(-1), respectively. At study end, UOP was lowest in dobutamine. Norepinephrine resulted in loss of ΔEVV fluid. data suggest a novel role for adrenergic receptors in regulating vascular and EVV expansion. β-Adrenergic agonists enhance vascular volume expansion, whereas α-adrenergic agonists eliminate extravascular fluid.
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High mobility group box 1 (HMGB1), a delayed mediator of proinflammatory cytokines, could initiate and amplify inflammatory responses to infection, injury, and other inflammatory stimuli, and it has emerged as a potential therapeutic target for inflammatory diseases. The overexpression of HMGB1 in endothelial cells has been proved to contribute to the development of these diseases. Because many proinflammatory cytokines expression were suppressed by thiazolidinediones (TZDs), agonists for nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), whether TZDs can inhibit HMGB1 expression and function is of great interest, however, it remains unknown. ⋯ A luciferase reporter assay showed that troglitazone inhibited not only the transcriptional activation of the HMGB1 promoter but also activities of heterologous promoters driven by nuclear factor κB (NF-κB) or activator protein 1 (AP-1) response elements. Altogether, these data suggest that NF-κB and AP-1 may participate in the inhibitory effect on HMGB1 transcription induced by troglitazone. Activation of PPARγ by troglitazone is effective for HMGB1 inhibition via suppressing NF-κB and AP-1 transcriptional activity in endothelial cells, which provides a new potential strategy to suppress excessive HMGB1 in inflammatory diseases.