1、江 洪 武汉大学人民医院心内科 心房颤动的研究现状 AF发生机制的再认识：对消融治疗的指导 AF发生机制的经典假说 多发子波 折返 局灶驱动 学说 主折返环伴 颤动样传导 局灶激动 肺静脉 Sleeve Haissaguerre et al. N Engl J Med 1998;339:659-66 肺静脉异常电活动驱动 AF 局灶激动 分布 Haissaguerre et al. N Engl J Med 1998;339:659-66 局灶激动的机制 1、自律性增加？ Perez-Lugones A et al, J Cardiovasc Electrophysiol 2003;14:80
2、3-809 Cheung J Physiol 314:445, 1980 From distal PV of superfused guinea pig atrium-lung prep (7/17) Approximately 30 bpm, increases in rate with 10-7M norepinephrine Wang et al Int J of Cardiol 89:187, 2003 Superfused canine PV preparations No examples of spontaneous activity observed (N = 50) Chen
3、 et al Cardiovasc Res 48:265, 2000 Automaticity present in 12 of 14 superfused canine PV preparations following rapid chronic atrial pacing (780 bpm) and 9 of 17 control PV preparations Arora et al Circulation 107:1816, 2004 66% in perfused canine atrium + PV preparations, 55 180 bpm in the presence
4、 of 10-6 M isoproterenol Cheung J Physiol 314:445, 1980 Wang et al Int J of Cardiol 89:187, 2003 Chen et al Cardiovasc Res 48:265, 2000 Arora et al Circulation 107:1816, 2004 自律性曾加 组织电生理研究 No Diastolic Depolarization PV Focal Firing Patterson E and Sunny Po, JACC. 2006 无舒张期除极：不支持自律性增加 LSPV LIPV PA A
5、O Firing PA View 肺静脉口部消融终止 Firing： 不支持自律性增加 PV Rapid Firing Micro- reentry Kalifa, Circulation. 2003 C D 局灶激动的机制 2、 PV内微折返 (Microreentry)? Sunny Po, JACC, 2006 0ms 32ms 64ms 128ms 早搏刺激：支持微折返 LAO Projection LSPV LIPV High Density 篮状电极标测 Patterson E, Sunny Po, JCE, 2007 肺静脉篮状电极标测：支持微折返 LSPV LIPV PA AO
6、 Firing PA View 肺静脉口部消融终止 Firing： 不支持微折返 Action Potential Intracellular Calcium (Calcium Transient) Based on 2 Properties of PV Myocardial Cells - Short action potential duration - Intracellular calcium concentration (calcium transient) remains high after repolarization Patterson et al, Heart Rhythm
7、 2005; 2:624 局灶激动的机制 3、 Triggered Activity Sinus Rhythm Rapid RhythmFollowed By Pause Rapid Rhythm Calcium Loading Pause Large Calcium Release From SR Action Potential Ca+Ca+ “Calcium-Transient Triggering” Hypothesis EADNa +/ Ca+ Exchanger (3 Na+ In 1 Ca+ Out) Net Inward Current (+) EAD Triggered Fi
8、ring EAD Action Potential Triggered Firing Increased Autonomic (GP) Activity Acetylcholine Shortens Action Potential Norepinephrine Increases Calcium Loading EADs Ca+ Ca+ Sinus Rhythm Rapid RhythmFollowed By Pause “Calcium-Transient Triggering” Hypothesis Acetylcholine (10-7M) + Norepinephrine (10-8
9、M) Pause-Induced Triggered Firing Canine LSPV Preparation 25 -25 -50 -75 0 200 ms S S 1.5 sec EAD EAD LSPV Micro- Electrode mV Patterson, Po, Scherlag, Lazzara, et al LSPV Bipolar SS Last 3 Beats of 20 Beat Train Cycle Length 180 ms (Rate 333/min) Triggered Firing Cycle Length 48 ms (1240/min) Aorta
10、 LA LSPV LIPV IVC RV LV RIPV 1 ARGP 5 RA SVC RPA RSPV Lasso Catheter 2 3 4 LOM PA View In Vivo Study Autonomic Mechanism for Focal Firing Lu Z, Jiang H, Po S. Unpublished. 1 = SLGP 2 = ILGP 3 = ARGP 4 = IRGP 5 = RPA-GP II HBE LSPVD2 LSPV34 LIPVD2 LIPV34 LAA LA RSPVD2 RIPVD2 RAA RA A H A HA A HA A HA
11、 200 msec 2:1 AV conduction block by HFS (1.5V) at the LSPV Lu Z, Jiang H, Sunny Po. Unpublished. S1-S2 train(30ms) II HBE LSPVD2 LSPV34 LIPVD2 LIPV34 LAA LA RSPVD2 RIPVD2 RAA RA 200 msec AV block by HFS (2.4V) just before initiation of AF Lu Z, Jiang H, Sunny Po. Unpublished. aVL HBE RSPVD2 RSPV34
12、RSPV56 RIPVD2 RIPV34 RIPV56 RAAD2 RAA34 RAD2 RA34 300 msec AF was initiated by HFS (1.5V) from RSPV Lu Z, Jiang H, Sunny Po. Unpublished. aVL HBE RSPVD2 RSPV34 RSPV56 RIPVD2 RIPV34 RIPV56 RAAD2 RAA34 RAD2 RA34 300 msec No AF by HFS (12V) after GP ablation Lu Z, Jiang H, Sunny Po. Unpublished. MR Ang
13、iogram - PA Projection Posterior SurfaceAnterior Surface Superior Left GP Inferior Left GP InferiorRight GP GPAxons Anterior Right GP Ganglionated Plexi (GP) 多发子波 折返 主折返环伴 颤动样传导 折返理论的基础心房重构 AF Begets AF Wijffels et al. Circulation 1995;92:195468 Duration of AF AF Begets AF的机制心房重构 Allessie et al. Car
14、diovascular Research 2002 心房电重构 Nattel et al. JICE. 2005 Chen PS et al. AJP. 2002 Focal Activity in Chronic Pacing induced AF Focal Activity in Chronic Pacing induced AF Chen PS et al. AJP. 2002 Right Thoracotomy Left Thoracotomy IVC RA RIPV RAA Anterior Right GP Inferior Right GP RSPV SVC LV LPA LS
15、PV LIPV RV LA Superior Left GP Inferior Left GPLAA Pacing 1200/min for 6 hrs LAA Lu Z, Jiang H and Sunny Po. Circ. 2008 心房电重构的神经机制 14 dogs EP Testing: ERP, AF Induction EP Testing: ERP, AF Induction EP Testing: ERP, AF Induction EP Testing: ERP, AF Induction 6 hr LAA pacing (1200/min) GP Ablation (A
16、RGP+IRGP+SLGP +ILGP+LOM) 6 hr LAA pacing (1200/min) GP Ablation (ARGP+IRGP+SLGP +ILGP+LOM) Group 1 Group 2 Group 1: Change in ERP During Atrial Pacing 200 160 120 80 40 1 2 3 4 5 6Baseline Duration of Rapid Atrial Pacing (Hours) ERP (ms) LSPV ERP 2 x Threshold ERP 10 x Threshold Lu Z, Jiang H and Su
17、nny Po. Circ. 2008 200 160 120 80 40 1 2 3 4 5 6Baseline ERP (ms) LSPV ERP 2 x Threshold ERP 10 x Threshold Post-Abl GP Ablation Group 1: Change in ERP after GP Ablation Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ. 2008 1 2 3 4 5 6Baseline WoV (ms) GP Ablatio n 0 400 800
18、 1200 1600 Post-Abl Group 1: Change in AF Inducibility Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ. 2008 200 160 120 80 40 1 2 3 4 5 6Post-Abl ERP (ms) LSPVGP Ablation After GP Ablation Group 2: Change in ERP During Atrial Pacing ERP 2 x Threshold ERP 10 x Threshold Dura
19、tion of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ. 2008 1 2 3 4 5 6Post-Abl 0 400 800 1200 1600 GP Ablation Group 2: No Change in AF Inducibility After GP Ablation WoV (ms) Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ. 2008 Mother Rotors and Fibrillator
20、y Conduction Jalife, et al. Circulation. 1998, 2000, 2001 Electrogram Across the Atria During AF SVC RAA Barrier IVC RAMid RSPV RIPV ARGP IRGP Ach RAAARAGP Lu Z, Jiang H and Sunny Po. JCE. 2008 II RAA RSPV RIPV RA AA Mid GP 100 ms Rotor Firing RA Fract + + + Electrogram Across the Atria During AF Lu
21、 Z, Jiang H and Sunny Po. JCE. 2008 Not Fibrillatory Conduction II RAA RSPV RIPV Before GP Ablation After GP Ablation RAAAMid GP 100 ms Rotor Firing Fract Not Firing Rotor (Slower) Much Less Fract Electrogram Across the Atria During AF Lu Z, Jiang H and Sunny Po. JCE. 2008 (%) 0 20 40 60 80 100 AA M
22、id GP AA Mid GP p0.05 p=NS ACh 10 mM on RAA Before Ablation After GP Ablation AA Mid GP AA Mid GP p=NS ACh 100 mM on RAA Before Ablation After GP AblationCFAE p0.01 p0.01 Electrogram Across the Atria During AF Lu Z, Jiang H and Sunny Po. JCE. 2008 RSPV RSPV Cardio-Cardiac Reflex RAA Ach (100 mM) on RAA or LAA Afferent Efferent Efferent Firing in RSPV (or LSPV) Neural Conduction !Lu Z, Jiang H and Sunny Po. JCE. 2008 GP In Fat Pad Thank you! Welcome to Renmin Hospital of Wuhan University!
