Effect of sertraline on ouabain-induced arrhythmia in isolated guinea-pig atria.
BACKGROUND
The effect of sertraline a selective serotonin reuptake inhibitor antidepressant was studied on ouabain-induced toxicity (arrhythmia) in spontaneously beating isolated guinea-pig atria.


METHODS
The guinea-pig atrium was dissected out and suspended in modified Krebs solution under physiological conditions. Drugs were added into solutions. The changes in rate and force of contractions were measured using a physiograph.


RESULTS
Sertraline (2-16 microg/mL) caused a dose-dependent decrease in the rate of contractions (17-46%) and in the contractile force (26-48%). Ouabain alone (1.2 microg/mL) produced arrhythmia at 7.8 min and asystole at 22 min. Pre- administration of the atria with sertraline (8 microg/mL) significantly increased the time required to produce arrhythmia by ouabain to 20.5 min, prolonged the beating of atria to more than 64.5 min and delayed the occurrence of asystolia. The pattern of contractile force induced by sertraline + ouabain was more regular than that produced by ouabain alone.


CONCLUSIONS
These findings indicate that sertraline produces direct cardiac action, probably due to the inhibition of cardiac Na(+) and Ca(2+) channels. Our results suggest that sertraline may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia.
Pousti
Abbas
A
Department of Pharmacology, Medical School, Tehran University of Medical Sciences, Tehran, Iran. drpousti@yahoo.com
Bakhtiarian
Azam
A
Najafi
Rouhallah
R
Deemyad
Tara
T
Brumand
Kaveh
K
Hosseini
Mir-Jamal
MJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology*; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D006168:Guinea Pigs; D006323:Heart Arrest / Q000139:chemically induced / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009924:Organ Culture Techniques; D010042:Ouabain / Q000633:toxicity*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D000928:Antidepressive Agents; D015220:Calcium Channels; D010042:Ouabain; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D015222:Sodium Channels