Katsumata1 N, Ma X, Higuchi H
Department of Pharmacology, Niigata University School of Medicine, 1-757 Asahimachi-dori, 951-8510, Niigata, Japan.
Eur J Pharmacol. 2000 Jun 9;398(1):83-91. doi: 10.1016/s0014-2999(00)00241-7.
Diltiazem has cardioprotective properties following myocardial ischemic injury. However, there are controversial results regarding the beneficial effects of diltiazem on regional myocardial flow after ischemia. Therefore, we investigated the effect of diltiazem on changes in regional myocardial flow due to ischemia for different periods. Non-radioactive colored microspheres were used for this measurement in isolated rat heart. After 20 or 40 min of global ischemia and 40 min of reperfusion, regional myocardial flow was decreased, especially in the endocardial layer. The endocardial/epicardial ratio was also decreased. The decreases in endocardial flow and the endocardial/epicardial ratio were more remarkable after 40 min of ischemia than after 20 min of ischemia. Diltiazem (10(-6) M), which was administered 15 min before ischemia, prevented only the decrease in endocardial flow and endocardial/epicardial ratio after 20 min of ischemia, whereas it did not prevent that after 40 min of ischemia. Nifedipine (2x10(-6) M) did not exert a cardioprotective effect. These findings suggested that the effect of ischemia is marked in the endocardium and, also, that the protective effect of diltiazem is seen only during a decrease in endocardial flow following short-term and reversible ischemia.
地尔硫䓬在心肌缺血性损伤后具有心脏保护特性。然而，关于地尔硫䓬对缺血后局部心肌血流的有益作用存在争议性结果。因此，我们研究了地尔硫䓬对不同时间段缺血所致局部心肌血流变化的影响。在离体大鼠心脏中使用非放射性彩色微球进行此项测量。在全心缺血20或40分钟以及再灌注40分钟后，局部心肌血流减少，尤其是在心内膜层。心内膜/心外膜比值也降低。缺血40分钟后的心内膜血流及心内膜/心外膜比值降低比缺血20分钟后更显著。在缺血前15分钟给予的地尔硫䓬（10⁻⁶ M）仅能预防缺血20分钟后的心内膜血流及心内膜/心外膜比值降低，而不能预防缺血40分钟后的降低。硝苯地平（2×10⁻⁶ M）未发挥心脏保护作用。这些发现表明，缺血作用在心内膜中显著，并且地尔硫䓬的保护作用仅在短期可逆性缺血后心内膜血流减少期间可见。
