Renmin Hospital of Wuhan University The 16 TH Great Wall International Congress of Cardiology 1...

1Renmin Hospital of Wuhan University

The 16TH Great Wall International Congress of Cardiology

Qingyan Zhao Congxin HuangDepartment of Cardiology, Renmin Hospital of Wuhan University

Vagal Stimulation and Differential Densities of Three Muscarinic Acetylcholine Receptors on Atrial Fibrillation in Canine Atria



Relation of AF and ACh or Vagus nerve

Vagal nerve stimulation (VNS) initiates and maintains AF Reentrant mechanism for AF in the presence of ACh Lack of IKACh prevents AF

Background



Background

Evidence has been provided with co-existence of the M2, M3 and probably also M4 in the atrium of dog and men



Background Effect of ACh on Atrial Myocardium

Vagal nervestimulation M2 recepterAChG protein

IKAChoutward

K+ current



Background Activation of M3/IKM3 by ACh shortens atrial ac

tion potential duration(APD)

The role of the M3 receptors in IKACh/IKM3 activation was found to be increased in AF



ObjectivesTo observe the different changes

of APD at atrial epicardium

VNS

ACh perfusion



Objectives Distribution of M receptor subtypes in atrial

myocardium was measured by western blot



Methods Experimental Animals

Ten dogs were abdomenly anesthetized with pentobarbital sodium

Heart was exposed in a pericardial cradle after a median sternotomy



Methods

Six custom-builtelectrode probes

Right atrial appendage (RAA)

High right atrium (HRA)

Low right atrium (LRA)

Left atrial appendage (LAA)

High left atrium (HLA)

Low left atrium (LLA)



Methods Experimental Protocol

Vagosympathetic trunks cutVagosympathetic trunks cut

VNSVNS

ACh perfusionACh perfusion



Methods AF and APD Recordings

Atrial premature beats, AT, AF APD50

APD90

dAPD



Methods Groups

Control group VNS group

ACh perfusion group



Methods Western Blot Analysis

After electrophysiological measurement, the hearts were quickly excised and RAA, LAA, LA and RA were dissected Distribution of M receptor subtypes in atrial myocardium were measured by western blot



Statistical Analysis

Data are expressed as x±s. Statistical comparisons were made on the basis of the variance analysis . Statistical significance was assumed if values were less than 0.05



Results Control group: atrial premature beats in two dogs

VNS group: atrial premature beats in ten

dogs , AT in 3 dogs , AF in 7 dogs

ACh perfusion group: atrial premature beats

in ten dogs , AT in 4 dogs , AF in 6 dogs



ResultsChanges of APD50

APD50(ms)

Effects of different intervention on APD50 in atrial epicardium0

1020304050607080

RAA HRA LRA LAA HLA LLA

control group VNS group Ach perfusi on group



ResultsChanges of APD90

APD90(ms)

Effects of different intervention on APD90 in atrial epicardium0

20406080

100120140160

RAA HRA LRA LAA HLA LLA

control group VNS group Ach perfusi on group



ResultsChanges of dAPD

dAPD(ms)

Effects of different intervention on dAPD in atrial epicardium0

5

10

15

20

25

30

APD50 APD90

control groupVNS groupAch perfusi on group



LLA

HLA

LAA

RAA

HRA

LRA

Comparison of the figures of MAP in control group, VNS group and ACh perfusion group



Results

LAA RAA LA RA (83kDa)

0

0. 5

1

1. 5

2Arbitrary Unit

P <0.05 vs RA; P <0.05 vs LALAA RAA LA RA



Results

LAA RAA LA RA (105kDa)Arbitrary Unit

P <0.05 vs LA and RALAA RAA LA RA

0

0. 5

1

1. 5

2



Results

LAA RAA LA RA (70kDa)Arbitrary Unit

P <0.05 vs LA and RALAA RAA LA RA

0

0. 5

1

1. 5

2



Discussion

Innervation heterogeneity in atria contributed to the ability of VNS in initiation of reentrant AF by increasing dispersion of refractoriness within atria Differences may participate in the ability of the LA to act as a "driver region" for AF

Recent studies



DiscussionOur studies

The distribution of M2, M3 and M4 in atrial myocardium is nonuniform. the heterogeneity of M2, M3 and M4 may be the reentrant mechanism for AF induced by VNS

APD was shortened and dAPD was increased by VNS and ACh, and AF was induced easily



DiscussionOur studies

Distribution of M2 and M3 receptors had higher density in LA than RA. However, there was no significant difference in APD between RA and LA APD that we observed was in epicardium but the heterogeneity of M2 and M3 may be present between epicardium and endocardium



Further Investigation The current densities of IKACh in different areas of atrium and atrial appendage

Selective IKACh blocker would be a novel antiarrhythmic drug



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Renmin Hospital of Wuhan University The 16 TH Great Wall International Congress of Cardiology 1...

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