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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Multiple organ failure is a common outcome of hemorrhagic shock followed by resuscitation, and the kidney is one of the prime target organs involved. The main objective of the study was to evaluate whether crocetin, a natural product from Gardenia jasminoides Ellis, has beneficial effects on renal dysfunction caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to reduce mean arterial blood pressure to 35 (SD, 5) mmHg for 60 min and then were resuscitated with their withdrawn shed blood and normal saline. ⋯ Hemorrhagic shock resulted in a significant elevation in malondialdehyde production and was accompanied by a reduction in total superoxide dismutase activity, activation of nuclear factor κB, and overexpression of inducible nitric oxide synthase. These changes were significantly attenuated by crocetin at 2 h after resuscitation. These results suggested that crocetin blocks inflammatory cascades by inhibiting production of reactive oxygen species and restoring superoxide dismutase activity to ameliorate renal dysfunction caused by hemorrhage shock and resuscitation.
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Randomized Controlled Trial Multicenter Study
Normal-range blood lactate concentration in septic shock is prognostic and predictive.
We hypothesized that lactate levels even within the normal range are prognostic and that low lactate levels predict a beneficial response to vasopressin infusion in septic shock. We conducted a retrospective analysis using the Vasopressin in Septic Shock Trial (VASST) as a derivation cohort (n = 665), then validated using another single-center septic shock cohort, St Paul's Hospital (SPH) cohort (n = 469). Lactate levels were divided into quartiles. ⋯ Lactate concentrations of 1.4 mmol/L or less predicted a beneficial response in those randomized to vasopressin compared with noradrenaline in VASST (P < 0.05). Lactate concentrations within the "normal" range can be a useful prognostic indicator in septic shock. Furthermore, patients whose lactate level is less than or equal to 1.4 mmol/L may benefit from vasopressin infusion.
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Systemic administration of α2-adrenergic agonists has been shown to protect ischemic myocardium, but the direct effects on ischemia-reperfused myocardium have not yet been clarified. This study was carried out to determine the effects of intracoronary dexmedetomidine (DEX) on the myocardial ischemia-reperfusion injury in anesthetized pigs. In open-chest pigs, the left anterior descending coronary artery was perfused through an extracorporeal circuit from the carotid artery. ⋯ Dexmedetomidine significantly improved the recovery of percentage segment shortening at 90 min after reperfusion (32.6% ± 3.1% in group C, 58.2% ± 2.1% in group LD, 61.1% ± 1.8% in group MD, and 72.0% ± 2.0% in group HD). Dexmedetomidine suppressed the increase in plasma norepinephrine concentration after reperfusion. The results indicate that DEX would exert the protective effect against ischemia-reperfusion injury by the direct action on the myocardium, which is not mediated through the central nervous system.
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Glucocorticoids remain a recommended therapy in advanced septic shock despite the often unpredictable response, and our understanding of the mechanisms regulating the steroid and stress response remains limited. Since the initial sequencing of the human glucocorticoid receptor α and β gene (hGRα and hGRβ), only three additional splice variants have been identified--all of which have been postulated to contribute to steroid resistance. During a survey of 97 healthy humans' blood, we identified two novel hGR splice isoforms (hGR-S1 and hGR-S1(-349A) retaining intron H between exons 8 and 9. ⋯ Removal of the 3' untranslated region (3'UTR) of the hGR-S1(-349A) mRNA sequence resulted in a loss of the augmented response. The isoform hGR-S1(-349A) augments the response to steroids, and this significant response appears to be critically regulated by the 3'UTR. The identification and evaluation of these unique hGR isoforms helps further the understanding of the complex genetic regulation of the stress and steroid response.