Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Cardiovascular Center, Chiba-Hokusoh Hospital, Nippon Medical School, Chiba, Japan.
Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Heart Rhythm. 2014 Apr;11(4):697-706. doi: 10.1016/j.hrthm.2013.12.032. Epub 2013 Dec 27.
Hypokalemia and sympathetic activation are commonly associated with electrical storm (ES) in normal and diseased hearts. The mechanisms remain unclear.
The purpose of this study was to test the hypothesis that late phase 3 early afterdepolarization (EAD) induced by IKATP activation underlies the mechanisms of ES during isoproterenol infusion and hypokalemia.
Intracellular calcium (Cai) and membrane voltage were optically mapped in 32 Langendorff-perfused normal rabbit hearts.
Repeated episodes of electrically induced ventricular fibrillation (VF) at baseline did not result in spontaneous VF (SVF). During isoproterenol infusion, SVF occurred in 1 of 15 hearts (7%) studied in normal extracellular potassium ([K(+)]o, 4.5 mmol/L), 3 of 8 hearts (38%) in 2.0 mmol/L [K(+)]o, 9 of 10 hearts (90%) in 1.5 mmol/L [K(+)]o, and 7 of 7 hearts (100%) in 1.0 mmol/L [K(+)]o (P <.001). Optical mapping showed that isoproterenol and hypokalemia enhanced Cai transient duration (CaiTD) and heterogeneously shortened action potential duration (APD) after defibrillation, leading to late phase 3 EAD and SVF. IKATP blocker (glibenclamide, 5 μmol/L) reversed the post-defibrillation APD shortening and suppressed recurrent SVF in all hearts studied despite no evidence of ischemia. Nifedipine reliably prevented recurrent VF when given before, but not after, the development of VF. IKr blocker (E-4031) and small-conductance calcium-activated potassium channel blocker (apamin) failed to prevent recurrent SVF.
Beta-adrenergic stimulation and concomitant hypokalemia could cause nonischemic activation of IKATP, heterogeneous APD shortening, and prolongation of CaiTD to provoke late phase 3 EAD, triggered activity, and recurrent SVF. IKATP inhibition may be useful in managing ES during resistant hypokalemia.
低钾血症和交感神经激活通常与正常和患病心脏中的电风暴（ES）相关。其机制尚不清楚。
本研究旨在检验以下假设，即在异丙肾上腺素输注和低钾血症期间，IKATP 的晚期 3 期早期后除极（EAD）的激活会引发 ES 的机制。
在 32 个 Langendorff 灌注的正常兔心中，通过光学映射来测量细胞内钙（Cai）和膜电压。
在基础状态下，反复发生电诱导的心室颤动（VF）并未导致自发性 VF（SVF）。在异丙肾上腺素输注期间，在正常细胞外钾浓度（[K+]o，4.5mmol/L）下，15 个心脏中有 1 个（7%）发生 SVF，在 2.0mmol/L [K+]o 下 8 个心脏中有 3 个（38%），在 1.5mmol/L [K+]o 下 10 个心脏中有 9 个（90%），在 1.0mmol/L [K+]o 下 7 个心脏中有 7 个（100%）（P<.001）。光学映射显示，异丙肾上腺素和低钾血症增强了除颤后的钙瞬变持续时间（CaiTD）并异质缩短了动作电位持续时间（APD），导致晚期 3 期 EAD 和 SVF。尽管没有缺血的证据，但 IKATP 阻断剂（格列本脲，5μmol/L）逆转了除颤后的 APD 缩短，并抑制了所有研究心脏中的复发性 SVF。硝苯地平在发生 VF 之前给予，而不是在发生 VF 之后给予，可靠地防止了复发性 VF。IKr 阻断剂（E-4031）和小电导钙激活钾通道阻断剂（apamin）不能防止复发性 SVF。
β-肾上腺素能刺激和伴随的低钾血症可能导致非缺血性 IKATP 激活、异质 APD 缩短和 CaiTD 延长，从而引发晚期 3 期 EAD、触发活动和复发性 SVF。IKATP 抑制可能有助于在难治性低钾血症期间管理 ES。
