ABSTRACT
In view of the importance of serotonin in the pathogenesis of myocardial infarction [MI] and the reported decrease in platelet serotonin concentration associated with the treatment with selective serotonin reuptake inhibitors [SSRIs], the present study was planned to test the hypothesis of decreased risk of MI associated with the use of SSRIs in rabbits exposed to myocardial ischemia reperfusion injury [MIRI], with or without cigarette smoking. The present study was conducted on 50 New Zealand White male rabbits grouped into: group I [sham-operated], group II [coronary artery ligated and reperfused for induction of MIRI], group III [smoking for eight weeks and then coronary artery ligated and reperfused], group IV [treated with fluoxetine for three weeks before coronary artery ligation and reperfusion] and group V [smoking for eight weeks and treated with fluoxetin for three weeks, starting from the 6[th] week of smoking, before coronary artery ligation and reperfusion]. Six hours following coronary artery ligation and reperfusion, relaxation response of left anterior coronary artery [LACA] segments to acetylcholine [Ach] was assessed and plasma cardiac troponin T[cTnT], homocysteine [Hcy] and urinary cotinine concentrations as well as percentage of platelet aggregation in response to adenosine diphosphate [ADP] were measured. MIRI resulted in a significant attenuation of ACh-induced relaxation in LACA segments compared to normal sham-operated rabbits. A significant decrease in Ach-induced relaxation in smoking MIRI compared to non-smoking MIRI rabbits could be also detected. A significant increase in percentage of platelet aggregation in response to ADP and in plasma Hcy and cTnT concentrations could be detected in MIRI rabbits compared to sham-operated rabbits with a significant difference between smoking and non-smoking MIRI rabbits. Fluoxetine treatment significantly improved endothelium-dependent relaxation to ACh in LACA segments obtained from nonsmoking and smoking MIRI rabbits. Fluoxetine treatment also resulted in significant decrease in plasma Hyc and cTnT concentrations and in percent of platelet aggregation compared to non-treated smoking and non-smoking MIRI rabbits. The data of the present study support the notion that platelets play a role in MI. It could be concluded that SSRIs could be protective against MI by inhibiting serotonin-mediated platelet activation and exerting favorable effect on endothelial function. Future clinical trials, well designed and carefully conducted should elucidate the potential benefits of SSRIs in multiple thrombotic events like MI and unstable angina