BACKGROUND: 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. METHODS AND RESULTS: In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post-left ventricular MI (6-15 weeks) dogs (n=5) compared with 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-reentry (1-3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine [0.1 µmol/L] or isoproterenol [0.01-0.1 µmol/L]) 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 or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentry. 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 versus 23±6% control; P<0.001). CONCLUSIONS: Both tachy- and brady-arrhythmias can result from SAN micro-reentry. Postinfarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry.
BACKGROUND: 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. METHODS AND RESULTS: In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post-left ventricular MI (6-15 weeks) dogs (n=5) compared with 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-reentry (1-3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine [0.1 µmol/L] or isoproterenol [0.01-0.1 µmol/L]) 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 or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentry. 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 versus 23±6% control; P<0.001). CONCLUSIONS: Both tachy- and brady-arrhythmias can result from SAN micro-reentry. Postinfarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry.
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