Antiplatelet Agents Sarpogrelate and Cilostazol Affect Experimentally-induced Ventricular Arrhythmias and Mortality

• Published in: Cardiovascular toxicology Vol. 8; no. 3; pp. 127 - 135
• Main Authors: Barta, Judit, Sanganalmath, Santosh K., Kumamoto, Hideo, Takeda, Nobuakira, Édes, István, Dhalla, Naranjan S.
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01-09-2008; Springer Nature B.V
• Subjects: Animals; Anti-Arrhythmia Agents - pharmacology; Arrhythmias, Cardiac - chemically induced; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - prevention & control; Biomedical and Life Sciences; Biomedicine; Cardiac arrhythmia; Cardiology; Coronary Occlusion - complications; Coronary Occlusion - drug therapy; Coronary Occlusion - metabolism; Cyclic AMP - metabolism; Disease Models, Animal; Electrocardiography; Epinephrine; Heart attacks; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Male; Pharmacology/Toxicology; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Succinates - pharmacology; Tetrazoles - adverse effects; Time Factors; Up-Regulation; Epinephrine; Cyclic AMP; Cilostazol; Coronary occlusion; Arrhythmias; Sarpogrelate
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-008-9019-x

Antiplatelet agents, sarpogrelate (SAR), a 5-hydroxy tryptamine 2A receptor antagonist and cilostazol (CIL), a phosphodiesterase-III inhibitor, were observed to be beneficial in attenuating cardiac remodeling and improving cardiac function in congestive heart failure due to myocardial infarction in rats; however, CIL increased ventricular tachycardia and mortality. In order to study the effects of these antiplatelet agents on arrhythmias, Sprague–Dawley rats were pretreated with either SAR or CIL (5 mg/kg/day) for 2 weeks and were then either injected cumulative doses of epinephrine (Epi) or subjected to coronary occlusion. Saline-treated animals served as controls. Electrocardiographic analysis revealed that SAR pretreatment decreased the incidence and severity of ventricular arrhythmias (time of onset of arrhythmias as well as the occurrence of premature ventricular contractions, salvos, tachycardia, and fibrillations), whereas CIL treatment augmented the incidence of cardiac arrhythmias due to both Epi and coronary occlusion. None of the drugs affected the corrected QT interval significantly. Furthermore, the levels of cyclic adenosine monophosphate (cAMP) in left ventricle were markedly higher in CIL-pretreated rats when compared to SAR-pretreated or control rats. It is suggested that an excessive level of cAMP may contribute to increase incidence of ventricular arrhythmias and mortality in animals pretreated with CIL, unlike the SAR-pretreated rats.