Furukawa T, Bassett A L, Furukawa N, Kimura S, Myerburg R J
Department of Medicine, University of Miami School of Medicine, Florida 33101.
J Clin Invest. 1993 Apr;91(4):1521-31. doi: 10.1172/JCI116358.
Left ventricular hypertrophy (LVH) potentiates reperfusion-associated ventricular fibrillation. To study the mechanism responsible, patch-clamp techniques were used to evaluate transmembrane ionic currents during "reperfusion" after a CN(-)-induced metabolic surrogate for ischemia in isolated myocytes from a feline model of experimental LVH. Reperfusion caused the generation of early afterdepolarizations (EADs) from an average take-off potential of -33 mV in LVH cells but not in cells from normal hearts. 10 min after initiating reperfusion of normal cells, action potential duration (APD) at 50% repolarization (APD50) lengthened from 198 +/- 41 to 233 +/- 57 ms whereas in LVH cells APD50 lengthened from 262 +/- 84 to 349 +/- 131 ms (P < 0.05). Among the LVH cells, APD50 lengthening was significantly greater in the cells that had developed EADs. During reperfusion, steady state outward current in the voltage range of the action potential plateau (between -20 and +20 mV) was reduced from the control values in LVH cells but not in normal cells. Reperfusion-related reduction of steady state outward current in LVH cells was abolished under experimental conditions in which L-type Ca2+ current was isolated from other classes of currents whereas it was still observed under the condition in which pure K+ currents could be recorded. Thus, reduction of steady state outward current due to the reduction of outward K+ current over the action potential plateau voltage range appears to be responsible for an excessive prolongation of APD, leading to the development of EADs.
左心室肥厚（LVH）会增强再灌注相关的心室颤动。为了研究其机制，采用膜片钳技术评估了在实验性LVH猫模型的离体心肌细胞中，用氰化物（CN⁻）诱导的缺血代谢替代物“再灌注”期间的跨膜离子电流。再灌注导致LVH细胞从平均-33 mV的起始电位产生早期后去极化（EADs），而正常心脏的细胞则未出现。正常细胞开始再灌注10分钟后，复极化50%时的动作电位时程（APD）从198±41毫秒延长至233±57毫秒，而LVH细胞的APD50从262±84毫秒延长至349±131毫秒（P<0.05）。在LVH细胞中，出现EADs的细胞其APD50延长更为显著。再灌注期间，动作电位平台期电压范围（-20至+20 mV之间）的稳态外向电流在LVH细胞中较对照值降低，而正常细胞则未降低。在将L型Ca²⁺电流与其他类型电流分离的实验条件下，LVH细胞中与再灌注相关的稳态外向电流降低被消除，而在能够记录纯K⁺电流的条件下仍可观察到。因此，在动作电位平台期电压范围内，由于外向K⁺电流减少导致的稳态外向电流降低似乎是APD过度延长的原因，进而导致EADs的发生。
