Early treatment with hydroxyethyl starch 130/0.4 causes greater inhibition of pulmonary capillary leakage and inflammatory response than treatment instituted later in sepsis induced by cecal ligation and puncture in rats

This study investigated the temporal profile of effects of hydroxyethyl starch (HES) 130/0.4 on pulmonary capillary leakage in a rat sepsis model induced by cecal ligation and puncture (CLP). Arterial blood pressure and heart rate were monitored during the experiment. Pulmonary capillary leakage was evaluated at 6, 12, 18, and 24 hr after CLP, and HES 130/0.4 was infused iv 2 hr prior to each time point. Myeloperoxidase (MPO) activity of lung homogenates and pulmonary levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-10, and nuclear factor-kappaB (NF-kappaB) activity were measured. Infusion of HES 130/0.4 attenuated the pulmonary capillary leakage, reduced the elevations of MPO, TNF-alpha, IL-6, and NF-kappaB levels, and further increased the IL-10 level. Infusion of HES 130/0.4 at 4 or 10 hr after the septic insult resulted in the greatest decreases in inflammatory mediators, suggesting that HES 130/0.4 is more protective against pulmonary capillary leakage when given early rather than later during sepsis.