232 Copyright © 2007 Sage Publications Plasma Endothelin-1 Levels in Septic Patients Mariusz Piechota, MD, PhD * Maciej Banach, MD, PhD † Robert Irzmanski, MD, PhD ‡ Marcin Barylski, MD ‡ Magdalena Piechota-Urbanska, MD § Jan Kowalski, MD, PhD ‡ Lucjan Pawlicki, MD, PhD ‡ Dysfunction of the vascular endothelium (ET) causes an increase in serum ET-1 concentration, as observed in sep- tic patients. It was assumed that in this patient population the ET-1 level correlates with the degree of sepsis severity, including the level of organ dysfunction and, in particular, the level of circulatory dysfunction. The aim of the present study was to assess the relationship between levels of ET-1 and levels of N-terminal brain natriuretic propeptide (NT- proBNP), procalcitonin (PCT), and C-reactive protein (CRP), as well as the Sepsis-related Organ Failure Assessment (SOFA) score in septic patients. PCT and CRP were used to estimate the level of sepsis severity; the SOFA score was used to estimate multiorgan dysfunction; and NT-proBNP was used as a marker of cardiac dysfunction. Twenty patients with sepsis and severe sepsis were included in the study. Blood serum ET-1, NT-proBNP, PCT, and CRP con- centrations were determined at specific time intervals, and the SOFA score was calculated. Mean ET-1, NT-proBNP, PCT, and CRP concentrations were 8.39 pg/ml ± 6.39 pg/mL, 140.80 pg/mL ± 84.65 pg/mL, 22.32 ng/mL ± 97.41 ng/mL, and 128.51 mg/L ± 79.05 mg/L, respectively. Correlation between ET-1 levels and levels of NT-proBNP, PCT, and CRP was .3879 (P < .001), .358 (P < .001), and .225 (P = .011), respectively. Mean SOFA score was 6.31 pts ± 3.75 pts. Correlation between the ET-1 levels and SOFA score was .470 (P < .001). Six patients (30%) died during the observation period of 28 days. ET-1 levels correlate with levels of NT-proBNP, PCT, and CRP, as well as the SOFA score in septic patients. Key words: Endothelin-1; Sepsis-related Organ Failure Assessment score; N-terminal brain natriuretic propeptide; procalcitonin; C-reactive protein; sepsis; severe sepsis Introduction Septic patients constitute the majority of intensive care unit (ICU) patients in Poland, with 31.5% hos- pitalized for sepsis, 14.6% for severe sepsis, and 6% for septic shock [1]. Septic shock is characterized by massive vasodilatation with low systemic vascular resistance and severe hypotension [2]. Endothelin-1 (ET-1) is one of the peptides that plays a significant role in maintaining vascular wall tone. ET-1 is a 21- amino-acid vasoactive peptide synthesized by many cell types [3,4]. ET-1 is formed from its biological precursor, big ET-1, a 38-amino-acid-long peptide that, after its synthesis in the cytoplasm, is cleaved by ET conversion enzyme to yield active ET-1 (amino acids 1–21) and a C-terminal fragment (amino acids 22–38) [3]. The vasoconstrictive power of ET-1 is 140-fold greater than that of big ET-1 [5]. In the normal, uninjured vasculature, endothelial cells synthesize ET; however, injury to the endothe- lial cells during disease states leads to an increase in levels of ET-1. This peptide is also synthesized by cardiac myocytes and cardiac fibroblasts [6,7]. ET-1 has been associated with vasospasm, vascular damage, cardiovascular remodeling. and inflamma- tion [7–9]. ET-1 also plays an important role in reg- ulating cardiac function and renal perfusion. In patients with severe sepsis, ET-1 plasma levels are markedly increased [10–13] and correlate signifi- cantly with renal function [10]. Clinical manifesta- tions of sepsis in newborns are accompanied by increased concentrations of ET-1 [12,13]. Myocardial dysfunction often accompanies severe sepsis and septic shock [14–16]. In order to From the * Department of Anaesthesiology and Intensive Care Unit, and the Departments of † Cardiology, ‡ Internal Diseases and Cardiological Rehabilitation, and § Pharmacy, Medical University of Lodz, Poland. Received Aug 8, 2006, and in revised form Sep 22, 2006. Accepted for publication Oct 11, 2006. Financial support for this study provided by Boleslaw Szarecki University Hospital, Lodz, Poland. Address correspondence to Maciej Banach, MD, PhD, Department of Cardiology, Medical University of Lodz, Poland 91-425, or e-mail: m.banach@termedia.pl. Piechota M, Banach M, Irzmanski R, et al. Plasma endothelin-1 levels in septic patients. J Intensive Care Med. 2007; 22:232-239 DOI: 10.1177/0885066607301444 ORIGINAL RESEARCH