Vermeulen J T, McGuire M A, Opthof T, Coronel R, de Bakker J M, Klöpping C, Janse M J
University of Amsterdam, Department of Clinical and Experimental Cardiology, The Netherlands.
Cardiovasc Res. 1994 Oct;28(10):1547-54. doi: 10.1093/cvr/28.10.1547.
The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment.
Ventricular trabeculae were harvested from failing human hearts (from patients undergoing cardiac transplantation) and from normal and failing rabbit hearts (combined volume and pressure overload). Trabeculae were superfused with normal Tyrode solution followed by a modified Tyrode solution, which mimicked the extracellular milieu in patients with severe heart failure. Modified Tyrode solution contained low potassium (3.0 mM), low magnesium (0.4 mM), and noradrenaline (1 microM).
During superfusion with normal Tyrode solution, early afterdepolarisations, delayed afterdepolarisations, and automaticity were not observed in trabeculae from failing hearts. In the modified Tyrode solution, early afterdepolarisations could be induced in 26% of control rabbit and 30% of failing rabbit trabeculae, but never in human trabeculae. During superfusion with the modified solution delayed afterdepolarisations or triggered activity could be induced in 50% of the human failing trabeculae, in 43% of the failing rabbit trabeculae, and in 9% of the normal rabbit trabeculae (p < 0.01); automaticity was observed in 44% of the human trabeculae, and in 7% of the failing rabbit trabeculae, but in none of the control rabbit trabeculae. In failing rabbit myocardium action potential duration was prolonged at cycle lengths > or = 350 ms, but not at shorter cycle lengths.
Delayed afterdepolarisations and automaticity, but not early afterdepolarisations, occur more frequently in myocardium from failing hearts, but only during superfusion with a modified Tyrode solution. This emphasises that the extracellular environment is important with respect to arrhythmogenesis in heart failure, apart from the fixed cellular defect due to heart failure per se. Prolongation of the action potential in failing hearts does not occur at physiological and higher heart rates and therefore cannot be regarded as a protective factor in the prevention of reentrant arrhythmias. The rate of triggered and automatic rhythms was slow. Therefore these mechanisms cannot be responsible for clinical ventricular tachycardias or fibrillation, but may serve as triggers for reentrant arrhythmias.
本研究旨在评估在正常及改变的细胞外环境下，衰竭的人类心脏以及正常和衰竭的兔心脏的心室小梁中触发活动和自律性的发生情况。
从接受心脏移植的患者的衰竭人类心脏以及正常和衰竭的兔心脏（联合容量和压力超负荷）中获取心室小梁。先用正常的台氏液对小梁进行灌流，然后用一种模拟严重心力衰竭患者细胞外环境的改良台氏液灌流。改良台氏液含有低钾（3.0 mM）、低镁（0.4 mM）和去甲肾上腺素（1 microM）。
在用正常台氏液灌流期间，未在衰竭心脏的小梁中观察到早期后去极化、延迟后去极化和自律性。在改良台氏液中，26%的对照兔小梁和30%的衰竭兔小梁可诱发出早期后去极化，但人类小梁中从未出现。在用改良液灌流期间，50%的人类衰竭小梁、43%的衰竭兔小梁和9%的正常兔小梁可诱发出延迟后去极化或触发活动（p<0.01）；44%的人类小梁和7%的衰竭兔小梁出现自律性，但对照兔小梁均未出现。在衰竭的兔心肌中，当心动周期长度≥350 ms时动作电位时程延长，但在较短心动周期长度时未延长。
延迟后去极化和自律性而非早期后去极化，在衰竭心脏的心肌中更频繁出现，但仅在使用改良台氏液灌流时。这强调了除心力衰竭本身导致的固定细胞缺陷外，细胞外环境对心力衰竭时心律失常的发生也很重要。衰竭心脏的动作电位在生理心率及更高心率时不会延长，因此不能被视为预防折返性心律失常的保护因素。触发和自律性节律的频率较慢。因此，这些机制不能解释临床室性心动过速或颤动，但可能作为折返性心律失常的触发因素。
