白细胞介素转化酶抑制剂HMR-3480对猪体内心肌顿抑的影响。

Influence of the interleukin-converting enzyme inhibitor HMR-3480 on myocardial stunning in pigs in vivo.

作者信息

Barthel Holger, Südkamp Hendrik, Ebel Dirk, Müllenheim Jost, Schlack Wolfgang, Preckel Benedikt

机构信息

Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf, Germany;

出版信息

Exp Clin Cardiol. 2007 Fall;12(3):125-31.

PMID:18650993

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2323758/

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.

CONCLUSION

ICE inhibition by HMR-3480 had no effect on myocardial stunning in pigs in vivo.

摘要

背景

促炎细胞因子白细胞介素-1β通过白细胞介素-1β转换酶（ICE）转化为其活性形式。循环细胞因子可能在缺血后促进心肌功能障碍（心肌顿抑）。

目的

研究HMR-3840抑制ICE是否能改善体内心肌顿抑。

方法

使用麻醉（异氟烷和芬太尼）的猪测量左心室（LV）压力、心输出量以及左前降支冠状动脉（LAD）和左旋支冠状动脉的血流量。通过超声测量前尖壁和后基底壁的收缩期壁增厚和平均收缩期增厚速度来评估局部心肌功能。动物接受10分钟的LAD闭塞，随后再灌注4小时。在缺血期间，或在缺血及再灌注的最初60分钟内，将ICE抑制剂（流量调整以达到冠状动脉血浆浓度为10μg/mL）（ISCH组，n = 7）或赋形剂（CON组，n = 7）经侧支注入LAD。

结果

所有组在缺血期间LAD闭塞均导致前尖壁出现收缩期向外运动（膨出）。在缺血期间给予ICE抑制剂或在再灌注期间给予（再灌注结束时在前尖壁），对功能恢复均无影响（收缩期壁增厚值为：CON组17.3±7.3%，ISCH组23.2±9.8%，REP组19.3±6.1%；平均收缩期增厚速度值为：CON组4.3±1.1mm/s，ISCH组6.1±3.9mm/s，REP组5.2±1.7mm/s；CON组与ISCH组或REP组比较，所有P值均无统计学意义）。HMR-3840对LAD血流量无影响（23.4±5.2mL/min对24.3±8.1mL/min；P无统计学意义）。再灌注期间对照组和治疗组的整体心肌功能（LV压力、LV压力最大上升速率和心输出量）无差异。