Abnormal intracellular calcium handling underlying T-Wave alternans and its hysteresis

作者：Bao, Mingwei^*; Zhang, Junxia; Huang, Congxin; Jiang, Hong; Liu, Jie; Zhao, Dongdong

来源：Cardiology, 2007, 108(3): 147-156.

DOI：10.1159/000096566

• ischemia
• arrhythmia
• alternans
• electrocardiography
• action potential
• T wave

Aims: To investigate the mechanism underlying T-wave alternans ( TWA) and its hysteresis under ischemia conditions. @@@ Methods: Transmembrane action potential (AP) from endocardial, M, and epicardial cells and monophasic AP ( MAP) from four epicardial sites were recorded in ventricular wedge preparation and in isolated intact rabbit heart, respectively. The AP/MAP duration (APD/ MAPD), effective refractory period (ERP), activation time, and APD/ MAPD restitution were determined under control and ischemia conditions. The effects of ryanodine (0.01 and 1 mu mol center dot l(-1)) on TWA, and the effects of low extracellular Ca2+ and 4-aminopyridine on its hysteresis were studied. Results: Ischemia shortened the APD/ MAPD and effective refractory period of all recording sites symmetrically, except the APD of M cells, which shortened markedly. In the ischemia group, TWA was induced within a cycle length ( CL) range from 160 to 250 ms, which corresponded to a diastolic interval region of 0-70 ms. In this diastolic interval region, the repolarization restitution curve was the steepest ( slope > 1.0). All TWA were accompanied by repolarization alternations. Low concentration ry-anodine ( 0.01 mu mol center dot l(-1)) facilitated TWA, high concentration (1 mu mol center dot l(-1)) abolished it. Alternans of calcium transient were observed in myocytes purfused with ischemia solution during rapid stimulation. Ryanodine (0.1 mu mol center dot l(-1)) abolished alternans of calcium transient, and ryanodine ( 0.01 mu mol center dot l(-1)) facilitated them. After 60 min pacing at a CL of 200 ms, TWA persisted until the initial several beats at a CL of 300 ms at which a TWA was exceptional. The suppression of hysteresis by low extracellular Ca2+ and 4-aminopyridine indicated an underlying role of the intracellular Ca2+ overload and transient outward current (I-to). Conclusion: TWA is principally due to repolarization alternans, which is secondary to steep APD/MAPD restitution, and relates to intracellular calcium cycling. Hysteresis relates to intracellular Ca2+ overload and I-to.

• 出版日期2007
• 单位武汉大学; 中国人民解放军广州军区武汉总医院