Helke C J, Souza J D, Gillis R A
Eur J Pharmacol. 1978 Sep 15;51(2):167-77. doi: 10.1016/0014-2999(78)90341-2.
The present study was performed to determine whether increases in the tissue content of serotonin creatinine SO4 in the periphery would influence the arrhythmogenic effect of deslanoside. This was accomplished by infusing serotonin into anesthetized cats exposed to a subarrhythmic dose of deslanoside, determining doses of deslanoside required to produce ventricular tachycardia and ventricular fibrillation, and determining ventricular pacemaker rate (obtained during vagal-induced sinus node suppression). It was found that animals receiving serotonin creatinine SO4 plus deslanoside exhibited a greater increase in ventricular rate during sinus node suppression than with 5-HT infusion alone. No corresponding increase in ventricular pacemaker rate during sinus node suppression was observed with creatinine SO4 plus deslanoside. In addition, the dose of deslanoside to produce ventricular fibrillation in these animals was significantly correlated with the increase in ventricular pacemaker rate seen during th 5-HT infusion in the presence of deslanoside. Studies were also performed to determine whether the arrhythmogenic interaction of serotonin with deslanoside was associated with alterations in either cardiac tissue, blood or plasma levels of serotonin and 5-hydroxyindoleacetic acid. The data revealed a significant correlation between serotonin content in the left ventricle and the dose of deslanoside required to produce ventricular fibrillation. These results suggest that exogenous serotonin interacts with deslanoside to enhance the arrhythmogenic action of deslanoside.
本研究旨在确定外周组织中血清素硫酸肌酐(serotonin creatinine SO4)含量的增加是否会影响去乙酰毛花苷的致心律失常作用。这是通过将血清素注入暴露于亚致心律失常剂量去乙酰毛花苷的麻醉猫体内来实现的,确定产生室性心动过速和室颤所需的去乙酰毛花苷剂量,并确定心室起搏率(在迷走神经诱导的窦房结抑制期间获得)。结果发现,接受血清素硫酸肌酐加去乙酰毛花苷的动物在窦房结抑制期间心室率的增加比单独输注5-羟色胺时更大。在给予硫酸肌酐加去乙酰毛花苷的情况下,窦房结抑制期间未观察到心室起搏率相应增加。此外,在这些动物中产生室颤的去乙酰毛花苷剂量与在去乙酰毛花苷存在下5-羟色胺输注期间观察到的心室起搏率增加显著相关。还进行了研究以确定血清素与去乙酰毛花苷的致心律失常相互作用是否与心脏组织、血液或血浆中血清素和5-羟吲哚乙酸水平的改变有关。数据显示左心室中血清素含量与产生室颤所需的去乙酰毛花苷剂量之间存在显著相关性。这些结果表明,外源性血清素与去乙酰毛花苷相互作用以增强去乙酰毛花苷的致心律失常作用。