-Original-

Dynamics and Source of Endothelin-1 and Interleukin-6 Following Coronary Reperfusion in Patients with Acute Myocardial Infarction

Takahiro Imaizumi^1,2, Jun Nejima^1,2,4, Kaname Kiuchi^1,2, Shinhiro Takeda^1,3, Yoshihiko Seino², Keiji Tanaka¹ and Teruo Takano²

¹Division of Intensive and Coronary Care Unit, Nippon Medical School
²Department of Functional Pathophysiology for Human Organs, Graduate School of Medicine, Nippon Medical School
³Department of Anesthesia and Pain Control, Graduate School of Medicine, Nippon Medical School
⁴Department of Internal Medicine, Tsurumi University School of Dental Medicine

Objectives: The goals of this study were to determine the source of circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) in acute myocardial infarction (MI) and to study the effects of coronary reperfusion (CR) on plasma levels of ET-1 and IL-6.
Methods: We serially measured plasma concentrations of ET-1 and IL-6 at different sampling sites before and after CR in patients with acute MI. A femoral vein (FV) catheter, a Swan-Ganz catheter, and a femoral artery (FA) catheter were placed in 25 patients with acute MI who were admitted within 12 hours after onset. For the measurement of ET-1 and IL-6 concentrations, blood samples from the FV, right atrium (RA), pulmonary artery (PA), and FA were collected before and 1 hour, 8 hours, and 24 hours after CR therapy. In 5 of the 25 patients, blood samples were collected through a coronary sinus (CS) catheter. We also assessed the gradient across 3 vascular beds (systemic, pulmonary, and coronary) as indices of the net release of ET-1 and IL-6 from those vascular beds. The maximal serum creatine kinase (CK) levels were assessed as an index of myocardial necrosis.
Results: ET-1 levels were higher in the FV than in the RA, PA, or FA. On CR, ET-1 levels peaked after 1 hour and returned to baseline by 24 hours. Calculated net release of ET-1 from the systemic vascular bed (ET-1 at FV-ET-1 at FA) was the highest among the 3 vascular beds. Plasma ET-1 levels correlated with hemodynamic parameters. Plasma IL-6 levels were similar among different sampling sites, whereas calculated net release of IL-6 from the coronary vascular bed was the highest among the 3 vascular beds. IL-6 levels increased throughout 24 hours after coronary reperfusion and closely correlated with maximal CK levels.
Conclusions: The present study suggests that, in acute MI, the major source of ET-1 maintaining baseline plasma levels is the systemic vascular bed and that the ET-1 levels presumably reflect the congestion. ET-1 levels peaked 1 hour after CR. IL-6 increased for 24 hours after CR. The major source of IL-6 is the coronary vascular bed. Only a slight correlation was observed between plasma ET-1 and IL-6 levels.

J Nippon Med Sch 2007; 74: 131-147

Keywords
acute myocardial infarction, coronary reperfusion, endothelin-1, interleukin-6, hemodynamics

Correspondence to
Jun Nejima, MD, Division of Intensive and Coronary Care Unit, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
nejima-j@tsurumi-u.ac.jp

Received, November 30, 2006
Accepted, January 15, 2007