Bunc M, Drevensek G, Budihna M, Suput D
Medical Faculty, Institute of Pathophysiology, Ljubljana, Slovenia.
Toxicon. 1999 Jan;37(1):109-23. doi: 10.1016/s0041-0101(98)00168-8.
Equinatoxin II is a lethal basic protein isolated from the sea anemone Actinia equina (L.) with LD50 in mice 35 microg/kg. The putative cause of death is cardiorespiratory arrest, but the mechanism of cardiotoxicity is poorly understood. It is not clear whether the toxin injected intravenously into an experimental animal reaches the heart in a concentration sufficient to cause direct effects on the heart. Therefore experiments were performed on rats and on isolated rat hearts in order to investigate the possible direct cardiotoxic effects of the toxin. For this reason the hearts were perfused with different concentrations of the toxin and with the effluent from the lungs collected during perfusion of the lungs with equinatoxin II. The results revealed the clear dose-dependent, direct cardiotoxic effects of the toxin and of the effluent from the lungs on Langendorff's heart preparations. The threshold concentration of equinatoxin II causing a drop in the perfusion rate, decreased left ventricular pressure, arrhythmia and increased LDH release, was found to be around 0.1 to 1 nM. With 10 nM equinatoxin II the left ventricular pressure dropped to 14+/-11% of the control, and the coronary flow to 9+/-3%. These effects were followed by arrhythmia and cardiac arrest. The concentration of equinatoxin recovered from the lungs after the perfusion with 100 nM equinatoxin II ranged between 0.8 and 5 nM. The results indicate that direct cardiotoxic effects of equinatoxin II play an important role in the lethal effects of the toxin.
海葵毒素II是从海葵(Actinia equina (L.))中分离出的一种致死性碱性蛋白,对小鼠的半数致死量为35微克/千克。推测其致死原因是心肺骤停,但对其心脏毒性机制了解甚少。尚不清楚静脉注射到实验动物体内的毒素是否能以足以对心脏产生直接影响的浓度到达心脏。因此,对大鼠和离体大鼠心脏进行了实验,以研究该毒素可能的直接心脏毒性作用。为此,用不同浓度的毒素以及在用海葵毒素II灌注肺脏期间收集的肺脏流出液对心脏进行灌注。结果显示,该毒素和肺脏流出液对Langendorff心脏标本具有明显的剂量依赖性直接心脏毒性作用。导致灌注率下降、左心室压力降低、心律失常以及乳酸脱氢酶释放增加的海葵毒素II的阈值浓度约为0.1至1纳摩尔。使用10纳摩尔海葵毒素II时,左心室压力降至对照组的14±11%,冠状动脉血流量降至9±3%。随后出现心律失常和心脏骤停。在用100纳摩尔海葵毒素II灌注后从肺脏中回收的海葵毒素浓度在0.8至5纳摩尔之间。结果表明,海葵毒素II的直接心脏毒性作用在该毒素的致死作用中起重要作用。