Nesiritide modulates inflammatory response during cardiac surgery: A pilot study

Abstract

Objectives: We investigated the effects of nesiritide (NES) on inflammatory response during cardiac surgery. Materials and Methods: Twenty-nine cardiac surgery patients were randomized to an infusion of NES at 0.01 mcg/kg/min for 48 h versus placebo (Ctrl). A panel of candidate biomarkers and clinical parameters were measured at predetermined time points. Results: There were no significant differences between the groups with regard to urine neutrophil gelatinase-associated lipocalin (NES 230.3 + 71.5 ng/mL vs. Ctrl 554.4 + 263.3 ng/mL, P = 0.253) and urine interleukin (IL)-18 (NES 29.9 + 4.8 pg/mL vs. 254.5 + 118.3 pg/mL, P = 0.090), or to the incidence of acute kidney injury (NES 7.1% vs. Ctrl 13.3%, P = 0.374). A concerted biomarker kinetic pattern of time-differentiated peak concentrations was observed. IL-10, inflammatory protein (IP)-10, IL-6, IL-10, IP-10, monocyte IP (MIP)-1α, interferon (IFN)-α, IFN-α, IL-1a, IL-3, and IL-7 reached peak concentration at 0 h following the end of cardiopulmonary bypass; tumor necrosis factor (TNF)-α, endothelial growth factor (EGF), granulocyte macrophage-colony-stimulating factor (GM-CSF), IL-12p40, IL-17, MIP-1α, and monocyte chemoattractant protein-1 at 1 h; IL-18, vascular EGF (VEGF), IL-13 and IL-1ra at 2 h, TNF-α, G-CSF, IL-1b, IL-2, IL-4, IL-5, and IL-15 at 4 h; and endothelin (ET)-1 and IL-18 at 6 h. At 0 h, the NES group exhibited significant reduction of peak concentrations of IL-6 (P = 0.009), IL-10 (P = 0.009), IL-1α (P = 0.020), IP-10 (P = 0.001), and IFN-α (P = 0.032) compared to the Ctrl group. Significant reduction in peak concentrations of TNF-α (P = 0.007) and MIP1-α (P = 0.027) at 1 h and ET-1 (P = 0.020) at 6 h in the NES group compared to the Ctrl group was noted. Conclusion: NES modulated the concerted inflammatory response in cardiac surgery and also attenuated ET-1 response, thus suggesting that previously observed favorable renal effect may be linked to reduced renal vasoconstriction.