Vos M A, van Deursen R T, Gorgels A P, Leunissen J D, Wellens H J
Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, The Netherlands.
Cardiovasc Res. 1993 Aug;27(8):1491-7. doi: 10.1093/cvr/27.8.1491.
R56865 has been described as a substance that protects cells from intracellular Na+ and Ca2+ overload. The aim of this study was to investigate its mechanism of action, which is at present unknown.
The haemodynamic and (rate dependent) electrophysiological effects of R56865 (0.48 mg.kg-1) were examined and compared with its antiarrhythmic effect on ouabain-induced ventricular tachycardia (n = 10), and ventricular tachycardia occurring within 24 h of occlusion of the left anterior descending artery (n = 8). The experiments were all performed in dogs.
In anaesthetised dogs R56865 increased (p < 0.05) the cycle length of the sinus rhythm, the corrected QT duration (+8%) and the effective refractory period (+16%) of the right ventricle. No rate dependency was found. R56865 had no effect on blood pressure, conduction, or refractoriness of the AV node, nor on conduction in the ventricle. In conscious dogs, R56865 did not change the cycle length of the sinus rhythm, but it did increase the QT duration (+5%, p < 0.05). The cycle length of the slower ouabain induced ventricular tachycardias which were terminated by R56865 increased to a greater extent (+55%) than that of the non-suppressible, faster ventricular tachycardias (+16%): 335(SD 30) ms, n = 5 v 285(10) ms, n = 5. The effect of R56865 on ventricular tachycardias 24 h after infarction was considered to be of minor antiarrhythmic importance.
R56865 has (1) class III effects, (2) a partial effect in terminating ouabain induced ventricular tachycardias which is inverse rate dependent, and (3) a weak effect on ventricular tachycardias 24 h after infarction.
R56865被描述为一种可保护细胞免受细胞内钠离子和钙离子过载影响的物质。本研究旨在探究其目前尚不明确的作用机制。
检测了R56865（0.48毫克/千克）的血流动力学和（心率依赖性）电生理效应，并将其对哇巴因诱发的室性心动过速（n = 10）以及左前降支动脉闭塞24小时内发生的室性心动过速（n = 8）的抗心律失常作用进行了比较。所有实验均在犬身上进行。
在麻醉犬中，R56865使窦性心律的周期长度增加（p < 0.05），右心室的校正QT间期增加（8%）以及有效不应期增加（16%）。未发现心率依赖性。R56865对血压、房室结传导或不应期以及心室传导均无影响。在清醒犬中，R56865未改变窦性心律的周期长度，但确实增加了QT间期（5%，p < 0.05）。被R56865终止的较慢的哇巴因诱发的室性心动过速的周期长度增加幅度（55%）大于不可抑制的较快室性心动过速（16%）：335（标准差30）毫秒，n = 5 对比 285（10）毫秒，n = 5。R56865对梗死后24小时室性心动过速的作用被认为抗心律失常意义不大。
R56865具有（1）Ⅲ类效应，（2）在终止哇巴因诱发的室性心动过速方面具有部分效应，且该效应呈反向心率依赖性，以及（3）对梗死后24小时的室性心动过速有微弱作用。
