van der Zee L, Wijffels M C, van Leuven C, Dorland R, Vos M A, Jongsma H J, Allessie M A
Department of Physiology, Cardiovascular Research Institute Maastricht, The Netherlands.
J Cardiovasc Electrophysiol. 2000 Nov;11(11):1262-9. doi: 10.1046/j.1540-8167.2000.01262.x.
Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AERP) and a decrease or reversal of its physiologic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AERP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes.
Following thoracotomy, MAPs were recorded from the free wall of the right atrium both before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats, MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132+/-4 msec during slow pacing (400-msec interval) to 86+/-10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80 during slow pacing was as short as 67+/-5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91+/-6 msec. Also, MAPD20 (20% repolarization) shortened (P = 0.05) from 32+/-4 msec (400 msec) to 14+/-7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20+/-3 msec (400 msec) to 33+/-5 msec (180 msec) in sustained AF. mRNA expression of the L-type Ca2+ channel alpha1c gene and Kv1.5 potassium channel gene, which underlie ICa and IKur, respectively, was reduced in sustained AF compared with sinus rhythm by 32% (P = 0.01) and 45% (P < 0.01), respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for Ito.
AF-induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of repolarization of the action potential are associated with changes in mRNA expression of the alpha subunit genes of the L-type Ca2+ channel and the Kv1.5 potassium channel.
持续性心房颤动（AF）的特征是心房有效不应期（AERP）显著缩短，以及其对心率的生理适应性降低或逆转。本研究的目的是调查山羊中AF诱导的AERP变化是否与心房单相动作电位（MAP）的变化相关，以及特定离子通道的异常表达是否是这些变化的基础。
在开胸后，对长期植入仪器的山羊在诱发AF之前（对照）和持续性AF（>2个月）复律后，从右心房游离壁记录MAP。在对照山羊中，80%复极化时的MAP持续时间（MAPD80）在慢起搏（400毫秒间期）时从132±4毫秒缩短（P<0.01）至快起搏（180毫秒）时的86±10毫秒。持续性AF复律后，慢起搏时的MAPD80短至67±5毫秒（电重构）。增加起搏频率导致MAPD80延长（P=0.02）至91±6毫秒。此外，对照山羊中，MAPD20（20%复极化）从32±4毫秒（400毫秒）缩短（P=0.05）至14±7毫秒（180毫秒），而在持续性AF中，其从20±3毫秒（400毫秒）延长（P=0.03）至33±5毫秒（180毫秒）。分别构成ICa和IKur的L型Ca2+通道α1c基因和Kv1.5钾通道基因的mRNA表达在持续性AF中与窦性心律相比分别降低了32%（P=0.01）和45%（P<0.01）。负责Ito的快速Na+通道、Na+/Ca2+交换体或Kv4.2/4.3通道的mRNA水平未发现显著变化。
山羊中AF诱导的电重构包括MAPD缩短及其生理速率适应性逆转。动作电位复极化时间进程的变化与L型Ca2+通道和Kv1.5钾通道α亚基基因的mRNA表达变化相关。
