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绵羊上腔静脉心肌套的耐火度
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上腔静脉(SVC)心肌套中的心肌细胞具有不同的动作电位和离子电流曲线,但尚未报道这些细胞的难治性。 使用标准的细胞内微电极技术,我们在绵羊中证明了SVC(114.7 +/- 6.5 ms)中心肌细胞的有效不应期(ERP)短于下腔静脉(lVC)(166.7 +/- 6.2)毫秒),右心房游离壁(RAFW)(201.0 +/- 6.0毫秒)和右心耳(RAA)(203.1 +/- 5.8毫秒)(P <0.05)。 右心房心肌细胞ERP被毒蕈碱型2型受体WA激动剂乙酰胆碱异质地缩短。 灌注15μM乙酰胆碱后,SVC中发生了最短的ERP(SVC,IVC,RAFW和RAA中的ERP为53.6 +/- 2.7、98.9 +/- 2.2、121.8 +/- 6.0和109.7 +/-分别为5.1毫秒; P <0.05)。 另一种M2R激动剂卡巴胆碱(1μM)产生的作用与乙酰胆碱相似。 此外,我们使用了甲基辛特拉明,一种M2R阻滞剂,4-DAMP,一种毒蕈碱3型受体(MA阻滞剂和tropicamide,一种毒蕈碱4型受体WA阻滞剂)来抑制乙酰胆碱引起的SVC心肌细胞ERP缩短。甲基辛特拉明,4-DAMP
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Refractoriness of the Sheep Superior Vena
Cava Myocardial Sleeve
CUIMEI ZHAO,*,
,1
JIE QI,*,
,1
XINGYUAN LIU,à
,1
HUAIZHI CHEN,*,à
,1
JUN LI,*, YI LIU,à
L
EI LIANG,*, YANGYANG ZHANG,* JUNJIE XIAO,,à LI LI,à LUYING PENG,à JIAHONG XU,*
J
UN MA,* YING YANG,* XIANZHENG WU,* AND YI-HAN CHEN*,,à
,2
*Department of Cardiology, Tongji Hospital, Heart Rhythm Research Center, and àInstitute of
Medical Genetics, Tongji University, Shanghai 200065, China
The cardiomyocytes in the superior vena cava (SVC) myocardial
sleeve have distinct action potentials and ionic current profiles,
but the refractoriness of these cells has not been reported.
Using standard intracellular microelectrode techniques, we
demonstrated in sheep that the effective refractory period
(ERP) of the cardiomyocytes in the SVC (114.7 6 6.5 ms) is
shorter than that in the inferior vena cava (IVC) (166.7 6 6.2 ms),
right atrial free wall (RAFW) (201.0 6 6.0 ms) and right atrial
appendage (RAA) (203.1 6 5.8 ms) (P < 0.05). The right atrial
cardiomyocyte ERP was heterogeneously shortened by acetyl-
choline, a muscarinic type 2 receptor (M
2
R) agonist. After
perfusion with 15 lM acetylcholine, the shortest ERP occurred
in the SVC (the ERP in the SVC, IVC, RAFW and RAA was 53.6 6
2.7, 98.9 6 2.2, 121.8 6 6.0 and 109.7 6 5.1 ms, respectively; P <
0.05). Carbachol (1 lM), another M
2
R agonist, produced a similar
effect as acetylcholine. Furthermore, we used methoctramine, a
M
2
R blocker, 4-DAMP, a muscarinic type 3 receptor (M
3
R)
blocker, and tropicamide, a muscarinic type 4 receptor (M
4
R)
blocker to inhibit the acetylcholine-induced ERP shortening of
SVC cardiomyocytes, and found that the 50% inhibitory
concentration for methoctramine, 4-DAMP and tropicamide
was 5.91, 45.72 and 80.34 nM, respectively. Therefore, we
conclude that the sheep SVC myocardial sleeve is a unique
electrophysiological region of the right atrium with the shortest
ERP both under physiological condition and under cholinergic
agonist stimulation. M
2
R might play a major role in the response
of the SVC myocardial sleeve to parasympathetic nerve tone.
The association between the distinct refractoriness in SVC and
atrial fibrillation originating from the region deserves further
investigation. Exp Biol Med 233:1441–1447, 2008
Key words: superior vena cava; myocardial sleeve; refractoriness;
acetylcholine; muscarinic type 2 receptor; atrial fibrillation
Introduction
Atrial fibrillation (AF) is the most common cardiac
arrhythmia encountered in clinical practice. The superior
vena cava (SVC) is one of the major ectopic foci initiating
paroxysmal AF. The other ectopic foci are the pulmonary
vein (PV), left atrial posterior free wall, ligament of
Marshall, crista terminalis, coronary sinus ostium and
interatrial septum. Up to 37% of non-PV ectopic foci for
paroxysmal AF are located in the SVC (1). The SVC can not
only trigger but also drive AF (2–5). Electrical isolation of
the arrhythmogenic vessel can abolish AF and reduce its
recurrence (1, 6, 7).
Although it is well known that the SVC ectopic activity
originates most frequently from the myocardial sleeve
connected to the right atrium in human and other
mammalian hearts (8–13), the reason for the increased
likelihood of ectopic activity in the myocardial sleeve
remains poorly understood. Abnormal automaticity, trig-
gered activity, and reentry are suggested as the electro-
physiological mechanisms (2, 7, 11, 14–16). The pacemaker
activity, after depolarization, and slow and anisotropic
conduction have been identified in the SVC myocardial
sleeve (11, 16–18). Further study by Chen and colleagues
demonstrates that the isolated atrial cardiomyocytes from
the SVC myocardial sleeve have distinct electrophysiolog-
ical properties including unique action potentials and ionic
current profiles (11). The autonomic nervous system is also
shown to play an important pathophysiological role in the
Support for this work was provided by the National Science Fund for Distinguished
Young Scholars (30425016), the National Science Fund of China (30330290,
30528011 and 30470961), the ‘‘973’’ (2007CB512100) and ‘‘863’’ Programmes
(2007AA02Z438) of China, the Programme Fund for Outstanding Medical Academic
Leader of Shanghai, China, the Programme Fund for Shanghai Subject Chief Scientist,
China, the Yangze Scholars Programme Fund by the Ministry of Education, China,
and the Programme Fund for Innovative Research Team by the Ministry of Education,
China (All of the grants were to Yi-Han Chen.).
1
These authors contributed equally to this work.
2
To whom correspondence should be addressed at the Department of Cardiology,
Tongji Hospital, Tongji University, 389 Xin Cun Road, Shanghai 200065, China. E-
mail: [email protected]
Received March 22, 2008.
Accepted June 11, 2008.
1441
DOI: 10.3181/0803-RM-102
1535-3702/08/23311-1441$15.00
Copyright Ó 2008 by the Society for Experimental Biology and Medicine
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