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
-
Randomized Controlled Trial
Isoproternenol Increases Efficiency and Effectiveness of a Large Fluid Bolus in Healthy Volunteers.
The primary goal of fluid therapy is to maintain fluid homeostasis. Commonly used isotonic crystalloids are only marginally effective and contribute to fluid excess syndrome. In patients with decreased cardiovascular reserve, fluid therapy alone is not sufficient to maintain end-organ perfusion. Therefore, inotropes or vasoactive drugs are used to supplement fluid infusion. Recent animal data suggest that coinfusion of adrenergic agents modulate the distribution of fluid between the vascular and extravascular/interstitial compartments after a fluid bolus. We sought to determine if this effect would translate in humans by coadministering a β-adrenergic agonist with fluid. ⋯ Isoproterenol, a nonselective β-adrenergic agonist, augments vascular volume expansion and eliminates extravascular volume via enhanced diuresis, which may in part be due to enhanced endothelial barrier function.
-
The objective of this study was to determine whether persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts mortality. ⋯ Persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts early and late mortality and may serve as a biomarker for sepsis-induced immunosuppression.
-
Hepatic ischemia-reperfusion (IR) results in progressive injury; initiated by oxidative stress during ischemia and compounded by cytokine-mediated inflammation during reperfusion. Recovery requires strict regulation of these events. Recombinant human erythropoietin (rhEPO) is thought to mitigate hepatocellular IR injury by altering the nonparenchymal liver microenvironment. ⋯ Although Socs3 and STAT5 activation were induced in normal liver after in vivo rhEPO injection, this treatment did not augment expression beyond that seen with IR alone, and neither was induced in cultured hepatocytes treated with rhEPO. Recombinant human erythropoietin inhibited caspase-3 activation in nonparenchymal cells, whereas hepatocellular HO-1 was rapidly induced both in vivo and in vitro with rhEPO treatment. These data suggest HO-1 as a potent mechanism of rhEPO-mediated protection after liver IR, which involves both direct hepatocellular and nonparenchymal mechanisms.
-
Nuclear factor erythroid 2-related factor 2 (NRF2) has been shown to protect against experimental sepsis in mice and lipopolysaccharide (LPS)-induced inflammation in ex vivo white blood cells from healthy subjects by upregulating cellular antioxidant genes. The objective of this study was to test the hypothesis that ex vivo methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate (CDDO-Me) activates NRF2-regulated antioxidant genes in white blood cells from patients with septic shock and protects against LPS-induced inflammation and reactive oxidative species production. Peripheral blood was collected from 18 patients with septic shock who were being treated in medical and surgical intensive care units. ⋯ Pretreatment with CDDO-Me followed by LPS exposure had no significant effect on O2 levels in purified monocytes. These data suggest that the NRF2 pathway is differentially responsive to CDDO-Me activation in peripheral blood cells from patients with septic shock and results in increased O2 production. The data may also suggest a suppressed NRF2 pathway in white blood cells from critically ill patients.
-
Trauma/hemorrhagic shock (T/HS) is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1-phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS-induced multiple organ dysfunction syndrome in a rodent T/HS model. ⋯ FTY720 limited T/HS-induced multiple organ dysfunction syndrome (lung injury, red cell injury, and neutrophil priming) as well as T/HS lymph bioactivity, although it did not limit gut injury.