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Blockade of 5-HT2A Receptors by Sarpogrelate Protects the Heart Against Myocardial Infarction in Rats

Rana M. Temsah, PhD

Kanwal Kumar, BSc

Hideo Kumamoto, DVM

Nobuakira Takeda, MD, PhD

Naranjan S. Dhalla, PhD, MD (Hon)

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

Background: It has been shown that serotonin (5-hydroxytryptamine, 5-HT) is involved in exacerbating vascular abnormalities; however, its role in mediating changes in cardiac function due to myocardial injury has yet to be established. This study examined the effect of sarpogrelate, a 5-HT_2A receptor blocker, in preventing cardiac dysfunction due to myocardial infarction (MI).

Methods and Results: Rats were treated 3 days before surgery with or without 5 mg.kg^-1.day^-1 sarpogrelate, and the left coronary artery was ligated for 3 weeks to induce MI. Sarpogrelate reduced the mortality from 40% to 30%, infarct size from 35% to 25%, and left ventricular end diastolic pressure from 15 mm Hg to 10 mm Hg in MI rats. Electrocardiographic (ECG) tracings showed a marked deviation in the ST-segment and prolongation of the QTc interval in MI rats during the 3 weeks; these changes were attenuated by sarpogrelate pretreatment. In another set of experiments, MI rats were treated with 5 mg.kg^-1.day^-1 sarpogrelate 1 hour after the surgery, and the hemodynamic and electrocardiograph changes were assessed at 3 weeks. This posttreatment was also found to reduce infarct size, improve cardiac function, and attenuate ECG changes.

Conclusions: Sarpogrelate attenuates cardiac dysfunction, infarct size, and changes in the ECG due to MI. These results also support the view that serotonin and 5-HT_2A may contribute to the deleterious effects of ischemic injury in the heart.

Key Words: myocardial infarction • serotonin receptor blocker • sarpogrelate • 5-HT2A receptor antagonism

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 7, No. 1, 53-59 (2002)
DOI: 10.1177/107424840200700i108


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