The effects of 5-HT4 receptor blockade and stimulation, during six hours of atrial fibrillation.
OBJECTIVE
Stimulation of atrial 5-HT4 receptors is associated with arrhythmias. Their blockade prolongs atrial effective refractory period (ERP), following short runs of atrial fibrillation (AF). The role of 5-HT4 receptors during longer periods of AF is unknown. In this study, we investigated the effects of the selective 5-HT4 receptor stimulation and blockade on porcine atria, during 6 h of AF.


METHODS
Atrial ERP, monophasic action potential (MAP) duration, time to sinus rhythm restoration (TSRR) and ERP/MAP ratio were assessed in 27 pigs, at baseline and every hour, during 6 h of AF, induced by rapid atrial pacing. Ten animals were used as controls, 10 were administered the selective 5-HT4 antagonist SB203186 and seven were administered the selective 5-HT4 agonist RS67333.


RESULTS
During the first few hours of fibrillation, ERP, MAP and TSRR were preserved in SB203186-treated pigs, while they were shortened in controls and RS67333-treated animals. After 6 h of arrhythmia, ERP and MAP were shortened in all three groups, but the decrease was less in SB203186-treated pigs. ERP/MAP ratio increased in controls and RS67333-treated animals, while it remained unchanged in SB203186-treated pigs. Towards the end of the AF period, four of the SB203186-treated pigs developed sustained atrial tachycardia.


CONCLUSIONS
Following short periods of AF, 5-HT4 receptors' blockade protects the porcine atria against ERP and MAP shortening, while their stimulation has the opposite result. This beneficial effect, though, is gradually diminished following longer periods of AF and atrial tachycardia may develop.
Leftheriotis
Dionyssios I
DI
2nd Department of Cardiology, Onassis Cardiac Surgery Center, 17674 Athens, Greece. dionle1@otenet.gr
Theodorakis
George N
GN
Poulis
Dimitrios
D
Flevari
Panagiota G
PG
Livanis
Efthimios G
EG
Iliodromitis
Efstathios K
EK
Papalois
Apostolos
A
Kremastinos
Dimitrios Th
DT
D000814:Aniline Compounds / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D058832:Serotonin 5-HT4 Receptor Antagonists; D013552:Swine
C088817:(1-piperidinyl)ethyl 1H-indole-3-carboxylate; D000814:Aniline Compounds; D000889:Anti-Arrhythmia Agents; D007211:Indoles; D010880:Piperidines; D058832:Serotonin 5-HT4 Receptor Antagonists; C107826:RS 67333