title: Influence of the interleukin-converting enzyme inhibitor HMR-3480 on myocardial stunning in pigs in vivo.
abstract: BACKGROUND
  The proinflammatory cytokine interleukin-1 beta is converted into its active form by interleukin-1 beta-converting enzyme (ICE). Circulating cytokines may promote myocardial dysfunction (stunning) after ischemia.
  
  
  OBJECTIVE
  To investigate whether ICE inhibition by HMR-3840 improves myocardial stunning in vivo.
  
  
  METHODS
  Anesthetized (isoflurane and fentanyl) pigs were used for measurement of left ventricular (LV) pressure, cardiac output and blood flow in the left anterior descending coronary artery (LAD) and left circumflex coronary artery. Regional myocardial function was assessed by sonomicrometry as systolic wall thickening and mean systolic thickening velocity in the anteroapical and posterobasal walls. The animals were subjected to 10 min of LAD occlusion followed by 4 h of reperfusion. The ICE inhibitor (flow-adjusted to achieve coronary plasma concentrations of 10 mug/mL) (ISCH, n=7) or the vehicle (CON, n=7) was infused via a side branch into the LAD during ischemia, or during ischemia and the first 60 min of reperfusion (REP, n=6).
  
  
  RESULTS
  Occlusion of the LAD resulted in systolic outward movement (bulging) of the anteroapical wall during ischemia in all groups. Infusion of the ICE inhibitor had no effect on functional recovery when given during ischemia or when given during reperfusion (at the end of reperfusion in the anteroapical wall, values for systolic wall thickening were: CON 17.3+/-7.3%, ISCH 23.2+/-9.8% and REP 19.3+/-6.1%; and values for mean systolic thickening velocity were: CON 4.3+/-1.1 mm/s, ISCH 6.1+/-3.9 mm/s and REP 5.2+/-1.7 mm/s; all P values not significant for CON versus ISCH or REP). LAD blood flow was not affected by HMR-3840 (23.4+/-5.2 mL/min versus 24.3+/-8.1 mL/min; P not significant). Global myocardial function (LV pressure, maximum rate of LV pressure increase and cardiac output) was not different between controls and treatment groups during reperfusion.
  
  
  CONCLUSIONS
  ICE inhibition by HMR-3480 had no effect on myocardial stunning in pigs in vivo.
authors.affiliation: Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf, Germany;
authors.forename: Holger
authors.initials: H
authors.lastname: Barthel
authors.forename: Hendrik
authors.initials: H
authors.lastname: Südkamp
authors.forename: Dirk
authors.initials: D
authors.lastname: Ebel
authors.forename: Jost
authors.initials: J
authors.lastname: Müllenheim
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlack
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel