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 x kg(-1) x 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 x kg(-1) x 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.
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 x kg(-1) x 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 x kg(-1) x 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.
Authors: Mohammed Ahmed Fouad Shalaby; Hekma A Abd El Latif; Mohamed El Yamani; May Ahmed Galal; Sherifa Kamal; Ikhlas Sindi; Raneem Masaood Journal: BMC Pharmacol Toxicol Date: 2021-10-26 Impact factor: 2.483
Authors: Mohammed Fouad Shalaby; Hekma A Abd El Latif; Mohamed El Yamani; May Ahmed Galal; Sherifa Kamal; Ikhlas Sindi Journal: Curr Ther Res Clin Exp Date: 2021-10-12