Bauer Alexander, Becker Ruediger, Dreyhaupt Jens, Voss Frederik, Kraft Patricia, Kelemen Kamilla, Senges-Becker Julia C, Katus Hugo A, Schoels Wolfgang
Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Europace. 2007 Mar;9(3):154-61. doi: 10.1093/europace/eul146. Epub 2007 Jan 25.
Patients with sustained ventricular tachyarrhythmias are at high risk for sudden cardiac death. The mechanisms leading to multiple temporally related episodes of ventricular fibrillation (VF) are not yet fully elucidated, and treatment options are limited. We investigated whether K(ATP)-channels could be involved in triggering VF.
We determined postarrhythmic changes of monophasic action potentials (MAP) after repetitive induction of VF in 32 Langendorff-perfused rabbit hearts.
Postarrhythmic action potential duration (APD) was significantly shorter compared with baseline (100 +/- 12 ms vs. 140 +/- 8 ms, P < 0.05). With increasing numbers of VF and shortening of recovery intervals between VF episodes (2 min) inducibility of VF increased, and abbreviation of APD became more prominent (90 +/- 5 ms vs. 130 +/- 4 ms, P < 0.05). Pre-treatment with the selective K(ATP) blocking agent HMR 1883 led to a significant increase of postarrhythmic APDs compared with control hearts (100 +/- 12 ms vs. 118 +/- 3 ms, P = 0.0013). Moreover, HMR 1883 significantly reduced inducibility of VF and increased the rate of successful defibrillation.
Repetitive episodes of VF result in postarrhythmic abbreviation of APDs, a phenomenon thought to be of potential relevance for incessant tachyarrhythmias in patients. Prevention of postarrhythmic MAP-shortening by HMR 1883 might be useful in suppressing VF.
持续性室性心律失常患者发生心脏性猝死的风险很高。导致多次与时间相关的心室颤动（VF）发作的机制尚未完全阐明，且治疗选择有限。我们研究了K（ATP）通道是否参与触发VF。
我们在32个Langendorff灌注兔心脏中重复诱发VF后，测定单相动作电位（MAP）的心律失常后变化。
心律失常后的动作电位时程（APD）与基线相比显著缩短（100±12毫秒对140±8毫秒，P<0.05）。随着VF次数增加以及VF发作之间的恢复间隔缩短（2分钟），VF的诱导性增加，APD的缩短变得更加明显（90±5毫秒对130±4毫秒，P<0.05）。与对照心脏相比，用选择性K（ATP）阻断剂HMR 1883预处理导致心律失常后APD显著增加（100±12毫秒对118±3毫秒，P=0.0013）。此外，HMR 1883显著降低了VF的诱导性并提高了成功除颤率。
反复发生的VF发作导致心律失常后APD缩短，这一现象被认为与患者持续性心律失常可能相关。HMR 1883预防心律失常后MAP缩短可能有助于抑制VF。
