Pan S J, Combs A B
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712-1074, USA.
Toxicol In Vitro. 1995 Jun;9(3):219-29. doi: 10.1016/0887-2333(95)00014-y.
Emetine is an old drug which is used primarily as a emetic in ipecac syrup and as an alternative amoebicide. The major problem with emetine is that chronic use causes severe cardiotoxicity. In order to explore the mechanism of emetine cardiotoxicity, simultaneous recordings of mechanical activity and electrocardiograms, and biochemical assays were performed on male Sprague-Dawley rat hearts perfused by the Langendorff technique. Emetine was perfused constantly at concentrations of 19 or 37 mum for 10 min. All of the effects of emetine were concentration dependent. The most significant toxicological effect was the large amounts of LDH which appeared in the coronary effluent. A significant degree of injury to the cardiac plasma membrane is indicated by this observation, since LDH normally is an intracellular enzyme. Such damage to the membrane might accumulate and lead to the chronic, cumulative cardiotoxicity observed clinically with emetine. The pharmacological effects of emetine perfusion included decreased contractility which occurred concurrently with P-R interval prolongation, QRS duration prolongation, and degeneration of the QRS waveform. Coronary flow increased early during emetine perfusion, but then dropped to below control levels. The atria were more delayed in their response to emetine and in their recovery following emetine than were the ventricles. The simultaneous measurement of several parameters is a useful technique for the study of cardiac toxicity.
依米丁是一种古老的药物，主要用作吐根糖浆中的催吐剂和替代杀阿米巴药。依米丁的主要问题是长期使用会导致严重的心脏毒性。为了探究依米丁心脏毒性的机制，采用Langendorff技术对雄性Sprague-Dawley大鼠心脏进行机械活动和心电图的同步记录以及生化分析。依米丁以19或37 μmol的浓度持续灌注10分钟。依米丁的所有作用均呈浓度依赖性。最显著的毒理学效应是冠状动脉流出液中出现大量乳酸脱氢酶（LDH）。这一观察结果表明心肌细胞膜受到了显著损伤，因为LDH通常是一种细胞内酶。这种膜损伤可能会累积，并导致临床上观察到的依米丁慢性累积性心脏毒性。依米丁灌注的药理作用包括收缩力下降，同时伴有P-R间期延长、QRS波时限延长和QRS波形退变。依米丁灌注早期冠状动脉血流量增加，但随后降至对照水平以下。心房对依米丁的反应及其在依米丁作用后的恢复比心室更延迟。同时测量多个参数是研究心脏毒性的一种有用技术。
