Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia

Department of Biological Regulation and Regenerative Surgery, Nippon Medical School Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo, Tokyo, Japan *Corresponding author. Department of Thoracic and Cardiovascular Surgery, Nippon Medical School Chiba-Hokuso Hospital, 1715, Kamagari, Inba, Chiba 270-1694, Japan. Tel.: +81-476-99-1835; fax: +81-476-99-1921. E-mail address : shaw{at}nms.ac.jp (M. Kambe). Sivelestat, a neutrophil elastase inhibitor, has been shown to attenuate pulmonary injury during ischemia and reperfusion by improving microcirculation and may be effective as a cardioprotective agent. Isolated rat hearts were Langendorff-perfused (constant pressure, 75 mmHg) with oxygenated Krebs–Henseleit bicarbonate buffer (KHB). The optimal sivelestat concentration at 19 µmol/l was revealed because left ventricular developed pressure (LVDP) recovery in 19 µmol/l sivelestat was highest among 0.19, 1.9, 19, 190, and 1900 µmol/l sivelestat (26±10, 33±7, 56±5*, 35±2, and 15±5%, respectively; * P