Abstract
BackgroundSepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis.MethodsAdult male Wistar rats were equipped with arterial and venous catheters and received an intravenous infusion of lipopolysaccharide (LPS, serotype O127:B8, 10 mg/kg over 30 minutes) or vehicle (SHAM, n = 6). Two hours later, endotoxemic animals were randomized to receive 10 mL/kg of either 4% HSA (LPS+4%HSA, n = 6), 20% HSA (LPS+20%HSA, n = 6) or 0.9% NaCl (LPS+0.9%NaCl, n = 6). No fluids were given to an additional 6 animals (LPS). Vessel density and perfusion were assessed in the skeletal muscle microcirculation with sidestream dark field videomicroscopy at baseline (t0), 2 hours after LPS injection (t1), after HSA infusion (t2) and 1 hour later (t3). The mean arterial pressure (MAP) and heart rate were recorded. Serum endothelin-1 was measured at t2.ResultsMAP was stable over time in all groups. The microcirculatory parameters were significantly altered in endotoxemic animals at t1. The infusion of both 4% and 20% HSA similarly increased the perfused vessel density and blood flow velocity and decreased the flow heterogeneity to control values. Microvascular perfusion was preserved in the LPS+20%HSA group at t3, whereas alterations reappeared in the LPS+4%HSA group.ConclusionsIn a rat model of normotensive endotoxemia, the infusion of 4% or 20% HSA produced a similar acute improvement in the microvascular perfusion in otherwise unresuscitated animals.
Highlights
Fluid resuscitation is a cornerstone in the management of septic patients; what the best fluid to use in this condition has not been fully established
mean arterial pressure (MAP) was stable over time in all groups
Microvascular perfusion was preserved in the LPS+20% human serum albumin (HSA) group at t3, whereas alterations reappeared in the LPS+4%HSA group
Summary
Fluid resuscitation is a cornerstone in the management of septic patients; what the best fluid to use in this condition has not been fully established. Albumin is primarily responsible for the plasma colloid osmotic pressure and is a natural plasma volume expander [2] It acts as a carrier for a number of endogenous and exogenous molecules, including drugs such as antibiotics, sedatives and anticoagulants [3], and has antioxidant [4] and anti-inflammatory properties [5]. Kremer et al [15] showed that 4% HSA administration increased survival and prevented endothelial dysfunction in endotoxemic mice, whereas HSA at higher concentrations was detrimental. These data were not confirmed by others, who showed a protective effect of hyperoncotic albumin on sepsis-induced intestinal and lung injury [16]. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis
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