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;14:803-8
2、09,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 norepinephrineWang et al Int J of Cardiol 89:187, 2003 Superfused canine PV preparations No examples of spontaneous activity observed (N = 50),Chen et
3、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 preparationsArora et al Circulation 107:1816, 2004 66% in perfused canine atrium + PV preparations, 55 180 bpm in the presence of 1
4、0-6 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,AO,Firi
5、ng,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,Firing,PA
6、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 ofPV Myocardial CellsShort action potential duration- Intracellular calcium concentration(calcium transient) remains highafter repolarization,Patterson et al, Heart Rhythm 2005; 2:624,局灶激动的机制
7、 3、 Triggered Activity,Sinus Rhythm,Rapid Rhythm Followed By Pause,Rapid Rhythm,Calcium Loading,Pause,Large Calcium Release From SR,Action Potential,Ca+,Ca+,EAD,Na+/ Ca+ Exchanger (3 Na+ In 1 Ca+ Out),Net Inward Current (+),EAD,Triggered Firing,EAD,Action Potential,Triggered Firing,Increased Autonom
8、ic (GP) Activity,AcetylcholineShortens Action Potential,NorepinephrineIncreases Calcium Loading,EADs,Ca+,Ca+,Sinus Rhythm,Rapid Rhythm Followed By Pause,Acetylcholine (10-7M) + Norepinephrine (10-8M),Pause-Induced Triggered Firing,Canine LSPV Preparation,25,-25,-50,-75,0,200 ms,S,S,1.5 sec,EAD,EAD,L
9、SPVMicro-Electrode,mV,Patterson, Po, Scherlag, Lazzara, et al,LSPV Bipolar,S,S,Last 3 Beats of20 Beat TrainCycle Length 180 ms(Rate 333/min),Triggered Firing Cycle Length 48 ms (1240/min),Aorta,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 Autono
10、mic Mechanism for Focal Firing,Lu Z, Jiang H, Po S. Unpublished.,II,HBE,LSPVD2,LSPV34,LIPVD2,LIPV34,LAA,LA,RSPVD2,RIPVD2,RAA,RA,A,H,A,H,A,A,A,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,R
11、SPVD2,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,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
12、,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 Angiogram - PA Projection,Posterior Surface,Anterior Surface,Superior Left GP,Inferior Left GP,Inferior Right GP,GP Axons,Anterior Right GP,Ganglionated Plexi (GP
13、),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. Cardiovascular 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 Pacin
14、g 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,LSPV,LIPV,RV,LA,Superior Left GP,Inferior Left GP,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,
15、AF Induction,EP Testing: ERP, AF Induction,EP Testing: ERP, AF Induction,6 hr LAA pacing (1200/min),GP Ablation (ARGP+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,200,160,120,80,40,1,2,3,4,5,6,Basel
16、ine,Duration of Rapid Atrial Pacing (Hours),ERP (ms),LSPV,ERP 2 x Threshold,ERP 10 x Threshold,Lu Z, Jiang H and Sunny Po. Circ. 2008,200,160,120,80,40,1,2,3,4,5,6,Baseline,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 Ra
17、pid Atrial Pacing (Hours),Lu Z, Jiang H and Sunny Po. Circ. 2008,1,2,3,4,5,6,Baseline, WoV (ms),GP Ablation,0,400,800,1200,1600,Post-Abl,Group 1: Change in AF Inducibility,Duration of Rapid Atrial Pacing (Hours),Lu Z, Jiang H and Sunny Po. Circ. 2008,200,160,120,80,40,1,2,3,4,5,6,Post-Abl,ERP (ms),L
18、SPV,GP Ablation,After GP Ablation,Group 2: Change in ERP During Atrial Pacing,ERP 2 x Threshold,ERP 10 x Threshold,Duration of Rapid Atrial Pacing (Hours),Lu Z, Jiang H and Sunny Po. Circ. 2008,1,2,3,4,5,6,Post-Abl,0,400,800,1200,1600,GP Ablation,Group 2: No Change in AF Inducibility,After GP Ablati
19、on, WoV (ms),Duration of Rapid Atrial Pacing (Hours),Lu Z, Jiang H and Sunny Po. Circ. 2008,Mother Rotors and Fibrillatory Conduction,Jalife, et al. Circulation. 1998, 2000, 2001,Electrogram Across the Atria During AF,Lu Z, Jiang H and Sunny Po. JCE. 2008,II,RAA,RSPV,RIPV,RA,AA,Mid,GP,100 ms,Rotor,F
20、iring,RA Fract,+,+,+,Electrogram Across the Atria During AF,Lu Z, Jiang H and Sunny Po. JCE. 2008,Not Fibrillatory Conduction,II,RAA,RSPV,RIPV,Before GP Ablation,After GP Ablation,Rotor,Firing,Fract,Not Firing,Rotor (Slower),Much Less Fract,Electrogram Across the Atria During AF,Lu Z, Jiang H and Su
21、nny Po. JCE. 2008,(%),0,20,40,60,80,100,p0.05,p=NS,ACh 10 mM on RAA,Before Ablation,After GP Ablation,p=NS,ACh 100 mM on RAA,Before Ablation,After GP Ablation,CFAE,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,Thank you!,Welcome to Renmin Hospital of Wuhan University!,
