It has long been known that the electrophysiological effects of many cardioactive drugs strongly depend on the rate dependent frequency. This was recognized first for class I antiarrhythmic agents: their V_max suppressive effect was attenuated at long cycle lengths. Later many Ca²⁺ channel blockers were also found to follow such kinetics. The explanation was provided by the modulated and the guarded receptor theories. Regarding the duration of cardiac action potentials (APD) an opposite frequency-dependence was observed, i.e. the drug-induced changes in APD were proportional with the cycle length of stimulation, therefore it was referred as “reverse rate-dependency”. The beat-to-beat, or short term variability of APD (SV) has been recognized as an important proarrhythmic mechanism, its magnitude can be used as an arrhythmia predictor. SV is modulated by several cardioactive agents, however, these drugs modify also APD itself. In order to clear the drug-specific effects on SV from the concomitant unspecific APD-change related ones, the term of “relative variability” was introduced. Relative variability is increased by ion channel blockers that decrease the negative feedback control of APD (i.e. blockers of I_Ca, I_Kr and I_Ks) and also by elevation of cytosolic Ca²⁺. Cardiac arrhythmias are also often categorized according to the characteristic heart rate (tachy- and bradyarrhythmias). Tachycardia is proarrhythmic primarily due to the concomitant Ca²⁺ overload causing delayed afterdepolarizations. Early afterdepolarizations (EADs) are complications of the bradycardic heart. What is common in the reverse rate-dependent nature of drug action on APD, increased SV and EAD incidence associated with bradycardia.

早已知道，许多心脏活性药物的电生理作用强烈取决于速率依赖性频率。对于I类抗心律不齐药物，这首先得到认可：在较长的周期内，其V _max抑制作用减弱。后来许多Ca ²⁺还发现通道阻滞剂遵循这种动力学。解释是由调节和守卫的受体理论提供的。关于心脏动作电位（APD）的持续时间，观察到相反的频率依赖性，即，药物诱导的APD变化与刺激的周期长度成正比，因此被称为“反向速率依赖性”。APD的逐次跳动或短期变化已被认为是重要的心律失常机制，其大小可用作心律失常的预测指标。SV由几种心脏活性剂调节，但是，这些药物也会改变APD本身。为了从伴随的非特异性APD变化相关的药物中清除对SV的药物特异性作用，引入了“相对变异性”一词。_Ca，I _Kr和I _Ks）以及胞质Ca ^2+的升高。心脏心律不齐也经常根据特征性心律（心动过速和缓慢性心律失常）进行分类。心动过速是心律失常的主要原因，因为伴随的Ca ²⁺超负荷导致去极化后的延迟。早期除极后（EAD）是心动过缓心脏的并发症。药物作用于APD的反向速率依赖性性质，与心动过缓相关的SV和EAD发生率升高是很常见的。