Yokoshiki H, Kohya T, Tomita F, Tohse N, Nakaya H, Kanno M, Kitabatake A
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Japan.
J Mol Cell Cardiol. 1997 May;29(5):1331-9. doi: 10.1006/jmcc.1996.0367.
The presence of left ventricular hypertrophy (LVH) is associated with an increased incidence of arrhythmias. Our previous study on hypertrophied rat hearts has demonstrated that regression of LVH prevents ischemia-induced lethal arrhythmias. To elucidate the underlying mechanism of the reduced incidence of arrhythmias in regression of LVH, we examined electrophysiological properties of both hypertrophied and regressed left ventricular cells. Hearts from spontaneously hypertensive rats (SHR) were used as LVH, and those from Wistar-Kyoto rats (WKY) served as control. SHR with regression of LVH (REG) was produced by captopril treatment. Action potentials and membrane currents of subendocardial left ventricular cells were compared by the whole-cell patch-clamp techniques. Although the membrane capacitance of SHR cells was significantly greater than that of WKY cells, that of REG cells was normalized to the control level. Prolonged action potential duration (APD) and reduced density of transient outward current (ito) in SHR cells was normalized by LVH regression (APD at 75% repolarization (ms) and ito density at +60 mV (pA/pF): WKY 36.1 +/- 4.2, 11.9 +/- 1.3, SHR 73.1 +/- 12.9, 5.2 +/- 0.7, REG 29.5 +/- 3.9, 10.4 +/- 2.0, P = 0.015, P = 0.001 v WKY). No significant differences were observed in the densities of steady-state outward current, inward rectifier current, and L-type Ca2+ current. The restoration of ito density by regression of LVH could normalize the prolonged APD in hypertensive LVH, which may be causally related to the reduced incidence of arrhythmias in LVH regression.
左心室肥厚（LVH）的存在与心律失常发生率增加相关。我们之前对肥厚大鼠心脏的研究表明，LVH的消退可预防缺血诱导的致死性心律失常。为阐明LVH消退时心律失常发生率降低的潜在机制，我们检测了肥厚和消退的左心室细胞的电生理特性。自发性高血压大鼠（SHR）的心脏用作LVH模型，Wistar-Kyoto大鼠（WKY）的心脏作为对照。用卡托普利治疗产生LVH消退的SHR（REG）。通过全细胞膜片钳技术比较左心室心内膜下细胞的动作电位和膜电流。虽然SHR细胞的膜电容显著大于WKY细胞，但REG细胞的膜电容恢复到对照水平。SHR细胞中延长的动作电位时程（APD）和瞬时外向电流（ito）密度降低通过LVH消退得以恢复正常（复极化75%时的APD（毫秒）和+60 mV时的ito密度（pA/pF）：WKY 36.1±4.2，11.9±1.3，SHR 73.1±12.9，5.2±0.7，REG 29.5±3.9，10.4±2.0，P = 0.015，P = 0.001 与WKY相比）。稳态外向电流、内向整流电流和L型Ca2+电流密度未观察到显著差异。LVH消退使ito密度恢复正常可使高血压LVH中延长的APD恢复正常，这可能与LVH消退时心律失常发生率降低有因果关系。
