Pye M P, Cobbe S M
Department of Medical Cardiology, Glasgow Royal Infirmary, UK.
Cardiovasc Res. 1996 Aug;32(2):248-57. doi: 10.1016/0008-6363(96)00080-6.
To assess the effects of cardiac failure due to doxorubicin cardiotoxicity or chronic myocardial infarction on arrhythmia induction, ventricular repolarization and refractoriness in isolated perfused rabbit hearts under different loading conditions.
Cardiac failure was induced by doxorubicin injection (1-1.25 mg.kg-1 twice weekly for 8 weeks, n = 16) or coronary ligation (n = 12), with 12 controls. Cardiac failure was defined by an echocardiographic ejection fraction < or = 0.40. Arrhythmia susceptibility was assessed by programmed ventricular stimulation and fibrillation threshold measurement during Langendorff and during working heart perfusion under baseline conditions and at maximum tolerated preload and afterload. Monophasic action potential duration, dispersion of refractoriness, conduction time and effective refractory period were measured at each level of load.
During unloaded (Langendorff) perfusion, there was a low incidence of arrhythmia induction in all hearts. Increasing load did not alter arrhythmogenesis significantly in normal hearts, but led to increases in arrhythmia inducibility and falls in fibrillation threshold which were significantly greater in failing than in non-failing hearts. Monophasic action potential duration was significantly (P < 0.05) shorter in failing than in non-failing hearts in the doxorubicin-treated [mean (s.e.m.) 140(2) vs. 147(2) ms] and post-infarction groups [146(2) vs. 154 (3) ms] during working heart perfusion. The shortening in action potential duration and effective refractory period during increased preload tended to be greater in failing than in non-failing hearts. There were no changes in conduction times in response to changes in loading.
The inducibility of ventricular arrhythmias is greater in failing than in non-failing hearts and is further enhanced by increases in preload. Shortening of repolarization and refractoriness due to increased preload may contribute to the increased risk of ventricular tachyarrhythmias and sudden death in cardiac failure.
评估阿霉素心脏毒性或慢性心肌梗死所致心力衰竭对不同负荷条件下离体灌注兔心脏心律失常诱发、心室复极化及不应期的影响。
通过注射阿霉素（每周两次，每次1 - 1.25mg·kg-1，共8周，n = 16）或冠状动脉结扎（n = 12）诱导心力衰竭，设12只动物作为对照。心力衰竭定义为超声心动图射血分数≤0.40。在Langendorff灌注和工作心脏灌注期间，通过程序心室刺激和颤动阈值测量评估心律失常易感性，测量在基线条件下、最大耐受前负荷和后负荷时的情况。在每个负荷水平测量单相动作电位持续时间、不应期离散度、传导时间和有效不应期。
在无负荷（Langendorff）灌注期间，所有心脏心律失常诱发率均较低。增加负荷在正常心脏中对心律失常发生无显著改变，但导致心力衰竭心脏的心律失常诱发率增加和颤动阈值降低，且心力衰竭心脏的变化显著大于非心力衰竭心脏。在工作心脏灌注期间，阿霉素治疗组[平均值（标准误）140(2)对147(2)ms]和心肌梗死后组[146(2)对154(3)ms]中，心力衰竭心脏的单相动作电位持续时间显著短于非心力衰竭心脏（P < 0.05）。前负荷增加时，心力衰竭心脏动作电位持续时间和有效不应期的缩短往往大于非心力衰竭心脏。负荷变化时传导时间无改变。
心力衰竭心脏的室性心律失常诱发率高于非心力衰竭心脏，且前负荷增加会进一步增强这种诱发率。前负荷增加导致的复极化和不应期缩短可能是心力衰竭时室性快速性心律失常和猝死风险增加的原因。
