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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Both the high-frequency component of systolic arterial pressure variability and systolic pressure variation (SPV) have been indicated to be strongly affected by respiratory effect and sensitively reflect circulating blood volume (CBV). We attempted to determine the best means reflecting CBV from various parameters using power spectrum analyses of systolic arterial pressure variability (PSSAPV) and heart rate variability (PSHRV), SPV, and pulse pressure variation during graded hemorrhaging and fluid resuscitation. Under isoflurane anesthesia and mechanical ventilation, rabbits in group S (n = 6) had hemorrhaging induced, whereas those in group H (n = 10) had hemorrhaging induced followed by fluid resuscitation. ⋯ The correlations between CBV and total power (TP, 0.04-2.00 Hz), high-frequency component (0.75-1.40 Hz), and low-frequency component (0.04-0.40 Hz) of PSSAPV were more significant as compared with SPV and pulse pressure variation, whereas no correlations were noted between CBV and PSHRV. To evaluate the regression models appropriately, Akaike information criterion was used, and TP of PSSAPV showed the lowest value. We concluded that TP of PSSAPV most sensitively reflected changes of CBV and that PSSAPV was the most useful parameter for evaluation of volume status as compared with conventional circulatory parameters.
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The cholinergic nervous system can inhibit the release of proinflammatory cytokines such as TNF-alpha from LPS-stimulated macrophages. Acetylcholine, the principal neurotransmitter of the vagus nerve, is the key mediator of this so-called cholinergic anti-inflammatory pathway, specifically interacting with alpha7 cholinergic receptors expressed by macrophages and other cell types to inhibit TNF-alpha production. The aim of the current study was to determine the capacity of the selective alpha7 cholinergic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21), administered locally into the airways, to inhibit LPS-induced inflammatory responses in the mouse lung in vivo. ⋯ Intranasal inoculation with GTS-21 also dose-dependently inhibited TNF-alpha release into the lung compartment after intrapulmonary delivery of LPS in mice in vivo, whereas IL-6 concentrations were not affected. However, GTS-21 did not influence the influx of neutrophils into bronchoalveolar lavage fluid elicited by LPS and increased the concentrations of the neutrophil-attracting chemokines cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein 2. These data indicate that local administration of GTS-21 inhibits TNF-alpha release in the lung during LPS-induced inflammation.
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Severe sepsis and septic shock are major causes of morbidity and mortality among children in pediatric intensive care units (PICUs) worldwide. Activated protein C (PC) is a critical endogenous regulator of coagulation and inflammation in patients with sepsis. However, the role of PC in pediatric sepsis is still obscure. ⋯ Also, there was no correlation between plasma PC activity and D-dimer levels (r = -0.07; P = 0.6). Importantly, the odds of dying were significantly higher in patients whose level of PC activity was less than 25% (odds ratio = 5.6; P = 0.02). Pediatric patients with septic shock demonstrate very low levels of PC activity, and this may be associated with an increased risk of death.
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Comparative Study
Norepinephrine and intestinal mucosal perfusion in vasodilatory shock after cardiac surgery.
Patients with norepinephrine-dependent vasodilatory shock after cardiac surgery (n = 10) were compared with uncomplicated postcardiac surgery patients (n = 10) with respect to jejunal mucosal perfusion, gastric-arterial PCO2 gradient, and splanchnic oxygen demand/supply relationship. Furthermore, the effects of norepinephrine-induced variations in MAP on these variables were evaluated in vasodilatory shock. Norepinephrine infusion rate was randomly and sequentially titrated to target MAPs of 60, 75, and 90 mmHg (0.25 +/- 0.24, 0.37 +/- 0.21, and 0.55 +/- 0.39 microg/kg per minute, respectively). ⋯ Jejunal mucosal perfusion, jejunal mucosal hematocrit, RBC velocity, gastric-arterial mucosal PCO2 gradient, splanchnic oxygen extraction, and splanchnic lactate extraction were not affected by increasing infusion rates of norepinephrine. In patients with norepinephrine-dependent vasodilatory shock after cardiac surgery, intestinal mucosal perfusion was higher, whereas splanchnic and gastric oxygen demand/supply relationships were impaired compared with postoperative controls, suggesting that intestinal mucosal perfusion is prioritized in vasodilatory shock. Increasing MAP from 60 to 90 mmHg with norepinephrine in clinical vasodilatory shock does not affect intestinal mucosal perfusion and gastric or global splanchnic oxygen demand/supply relationships.
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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulates diverse biological functions including inflammation. The PPARgamma ligands have been reported to exert cardioprotective effects and attenuate myocardial reperfusion injury. Here, we examined the molecular mechanisms of their anti-inflammatory effects. ⋯ The cardioprotection afforded by ciglitazone was attenuated by the PPAR-gamma antagonist GW-9662. In contrast, GW-9662 did not affect the beneficial effects afforded by 15d-PGJ2. Thus, our data suggest that treatment with these chemically unrelated PPAR-gamma ligands results in diverse anti-inflammatory mechanisms.