Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness.
Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness.
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DOI：
10.1161/circep.113.000404
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Fedorov VV
中科院分区：
文献类型：
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作者：
Glukhov AV;Hage LT;Hansen BJ;Pedraza-Toscano A;Vargas-Pinto P;Hamlin RL;Weiss R;Carnes CA;Billman GE;Fedorov VV
涉及窦房结（SAN）的折返性心律失常，即SAN折返，仍然是心脏电生理学中最有趣的谜团之一。本研究的目的是阐明犬心脏 SAN 微折返与心肌梗死 (MI) 后结构重塑的机制。在体内，动态心电图监测显示，与对照狗 (n=4) 相比，左心室 MI 后 (6-15 周) 狗 (n=5) 出现室性心律失常和 SAN 功能障碍。在体外，对来自 MI (n=5) 和对照 (n=4) 的冠状动脉灌注心房制剂进行壁内 SAN 激活的高分辨率近红外光学测绘。在心房快速起搏（5-8 Hz）终止后，在中等自主神经刺激（乙酰胆碱（0.1 µM）或异丙肾上腺素（0.01-0.1 µM））期间，60% 的 MI 制剂中观察到 SAN 宏观折返（慢-快；16-28 mm）和微折返（1-3 mm），这一发现在对照中未见。自主神经刺激引起 SAN 不应期的异质变化；因此，相互竞争的心房波和/或 SAN 起搏器波可以产生单向阻滞并启动结内微折返。尽管心房心电图形态与常规窦性心律相同，但微折返枢轴波锚定于纵向阻滞区域并产生心动过速和矛盾性心动过缓（由于退出阻滞）。结内纵向传导阻滞与 MI SAN 起搏器复合体中夸大的间质纤维化股一致（纤维化密度 37±7% MI 与 23±6% 对照，P<0.001）。 SAN 微折返可能导致快速心律失常和缓慢心律失常。梗死后重塑，包括增加的结内纤维化和不应性的异质性，为 SAN 折返提供了基础。
Reentrant arrhythmias involving the sinoatrial node (SAN), namely, SAN reentry, remain one of the most intriguing enigmas of cardiac electrophysiology. The goal of the present study was to elucidate the mechanism of SAN micro-reentry in canine hearts with post myocardial infarction (MI) structural remodeling. In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post left ventricular MI (6–15 wks) dogs (n=5) compared to control dogs (n=4). In vitro, high resolution near-infrared optical mapping of intramural SAN activation was performed in coronary perfused atrial preparations from MI (n=5) and controls (n=4). Both SAN macro- (slow-fast; 16–28 mm) and micro-reentries (1–3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine (0.1 µM) or isoproterenol (0.01-0.1 µM)) after termination of atrial tachypacing (5–8 Hz), a finding not seen in controls. The autonomic stimulation induced heterogeneous changes in the SAN refractoriness; thus, competing atrial and/or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentries. The micro-reentry pivot waves were anchored to the longitudinal block region and produced both tachycardia and paradoxical bradycardia (due to exit block), despite an atrial ECG morphology identical to regular sinus rhythm. Intranodal longitudinal conduction blocks coincided with interstitial fibrosis strands that were exaggerated in the MI SAN pacemaker complex (fibrosis density 37±7% MI vs. 23±6% control, P<0.001). Both tachy- and bradyarrhythmias can result from SAN micro-reentries. Post-infarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry.