Killeen M J, Thomas G, Gurung I S, Goddard C A, Fraser J A, Mahaut-Smith M P, Colledge W H, Grace A A, Huang C L-H
Physiological Laboratory, University of Cambridge, Cambridge, UK.
Acta Physiol (Oxf). 2007 Jan;189(1):33-46. doi: 10.1111/j.1748-1716.2006.01643.x.
Hypokalaemia is associated with a lethal form of ventricular tachycardia (VT), torsade de pointes, through pathophysiological mechanisms requiring clarification.
Left ventricular endocardial and epicardial monophasic action potentials were compared in isolated mouse hearts paced from the right ventricular epicardium perfused with hypokalaemic (3 and 4 mm K(+)) solutions. Corresponding K(+) currents were compared in whole-cell patch-clamped epicardial and endocardial myocytes.
Hypokalaemia prolonged epicardial action potential durations (APD) from mean APD(90)s of 37.2 +/- 1.7 ms (n = 7) to 58.4 +/- 4.1 ms (n =7) and 66.7 +/- 2.1 ms (n = 11) at 5.2, 4 and 3 mm K(+) respectively. Endocardial APD(90)s correspondingly increased from 51.6 +/- 1.9 ms (n = 7) to 62.8 +/- 2.8 ms (n = 7) and 62.9 +/- 5.9 ms (n = 11) giving reductions in endocardial-epicardial differences, DeltaAPD(90), from 14.4 +/- 2.6 to 4.4 +/- 5.0 and -3.4 +/- 6.0 ms respectively. Early afterdepolarizations (EADs) occurred in epicardia in three of seven spontaneously beating hearts at 4 mm K(+) with triggered beats followed by episodes of non-sustained VT in nine of 11 preparations at 3 mm. Programmed electrical stimulation never induced arrhythmic events in preparations perfused with normokalemic solutions yet induced VT in two of seven and nine of 11 preparations at 4 and 3 mm K(+) respectively. Early outward K(+) current correspondingly fell from 73.46 +/- 8.45 to 61.16+/-6.14 pA/pF in isolated epicardial but not endocardial myocytes (n = 9) (3 mm K(+)).
Hypokalaemic mouse hearts recapitulate the clinical arrhythmogenic phenotype, demonstrating EADs and triggered beats that might initiate VT on the one hand and reduced transmural dispersion of repolarization reflected in DeltaAPD(90) suggesting arrhythmogenic substrate on the other.
低钾血症与一种致命形式的室性心动过速（VT）——尖端扭转型室速相关，其病理生理机制尚待阐明。
在灌注低钾（3和4 mmol/L [K⁺]ₒ）溶液的情况下，对从右心室心外膜起搏的离体小鼠心脏的左心室心内膜和心外膜单相动作电位进行比较。在全细胞膜片钳记录的心外膜和心内膜心肌细胞中比较相应的K⁺电流。
低钾血症使心外膜动作电位时程（APD）延长，在5.2、4和3 mmol/L [K⁺]ₒ时，平均APD₉₀分别从37.2±1.7 ms（n = 7）延长至58.4±4.1 ms（n = 7）和66.7±2.1 ms（n = 11）。心内膜APD₉₀相应地从51.6±1.9 ms（n = 7）增加至62.8±2.8 ms（n = 7）和62.9±5.9 ms（n = 11），心内膜 - 心外膜差值ΔAPD₉₀分别从14.4±2.6减小至4.4±5.0和 - 3.4±6.0 ms。在4 mmol/L [K⁺]ₒ时，7个自发搏动心脏中的3个心外膜出现早期后除极（EADs），在3 mmol/L时，11个标本中有9个出现触发搏动，随后是非持续性室速发作。程序电刺激在灌注正常钾溶液的标本中从未诱发心律失常事件，但在4和3 mmol/L [K⁺]ₒ时，分别在7个标本中的2个和11个标本中的9个诱发了室速。在离体心外膜而非心内膜心肌细胞（n = 9）中，早期外向K⁺电流在3 mmol/L [K⁺]ₒ时相应地从73.46±8.45降至61.16±6.14 pA/pF。
低钾血症小鼠心脏重现了临床致心律失常表型，一方面表现出可能引发室速的EADs和触发搏动，另一方面表现出反映在ΔAPD₉₀中的复极跨壁离散度降低，提示有致心律失常基质。
