| Objective: thromboembolic disease is one of the major lethal diseases, and the platelet activation, adhesion, aggregation, thrombosis release is an important mechanism which the thrombus starts, and this course plays a key role in the artery thrombosis and microvascular thrombosis. The thrombosis which is based on the vascular intimal injury and plaque rupture is an important part of acute attack to a number of thromboembolic diseases. Acute coronary syndrome is a group of acute clinical syndrome, which of pathology foundation is based on coronary atherosclerotic plaque rupture, and secondary complete or incomplete occlusive thrombosis. Its coronary artery has the common pathophysiological changes, that is, coronary atherosclerotic plaque transfers from stable to unstable, and then rupts leading to thrombosis. The platelet thrombus formation is the primary link during the occurrence and development of acute coronary syndrome. The platelet aggregation rate is used for the detection of platelet aggregation, which is an important indicator of platelet activity. Therefore, the anti-platelet aggregation plays an extremely vital role in prevention and treatment of this kind of disease. Aspirin and clopidogrel are the most widely used antiplatelet agents for preventing and treating vascular events. Aspirin affords cardioprotection through the acetylation of serine529 in human cyclooxygenase-1 (COX-1) of anucleated platelets, inducing a permanent defect in thromboxane A2 (TXA2)–dependent platelet function. We usually use enteric-coated aspirin in clinic. Clopidogrel is a potent adenosine diphosphate receptor blocker that irreversibly inhibits platelet aggregation by binding the ADP receptors (P2Y12) to prevent the activation of the glycoprotein IIb/IIIa pathway. At present, the domestic conventional doses recommended for patients with coronary artery disease are 100mg / d and 75mg / d respectively. Because of the two complementary mechanisms, clopidogrel plus aspirin, known as dual antiplatelet therapy, is highly effective in patients with a variety of high-risk clinical conditions such as acute coronary syndrome, and the efficacy and safety of the joint application have been confirmed. Coronary heart disease and other cardiovascular and cerebrovascular events occur in the existence of circadian rhythm changes.But at home and abroad there were few studies on diurnal variation in platelet activity of the patients with coronary heart disease after treatment and whether there were different effects on platelet activity for such patients when took anti-platelet drugs at different time, so at present the taking time of these two kinds of anti-platelet drugs has not yet reached a consensus. In this experiment, we study the effect of the different taking medicine time on the circadian rhythm changes in platelet aggregation of the patients with coronary heart disease, in order to choose a more effective taking medicine time and thus guide the clinical treatment. And in this study we also discuss after treatment the circadian rhythm in platelet aggregation of patients with the coronary heart disease, thus identify the characteristic changes of the time after the conventional anti-platelet therapy.Subjects: A total of 30 male patients diagnosed as the coronary heart disease (mean age 25.20±1.10 years) were selected, including 17 patients with unstable angina, 10 with ST-segment elevation myocardial infarction and 3 with Non-ST-segment elevation myocardial infarction. They were randomly divided into daytime and night-time medication group, and the two groups carried out cross-over.Methods: Daytime group: Blood samples were obtained at 10:00, 16:00, 20:00, 0:00 and 6:00 in one day after taking Aspirin 100mg and clopidogrel 75mg at 8:00am once a day for 5 days, when Plasma concentration reached steady state. Aggregation was assessed with a mobile four-channel whole blood impedance aggregometer (Chronolog-Log Corporation),and the platelet aggregation in the whole blood induced by ADP (10μmol/L) and arachidonic acid (10μmol/L). Evening Group:Blood samples were obtained at 10:00, 16:00, 20:00 , 0:00and6:00 in one day after taking Aspirin 100mg and clopidogrel 75mg at 8:00pm once a day for another 5 days, when Plasma concentration reached steady state and platelet aggregation was assessed in the same method .The two groups have carried out Successively. In the trial the error that caused by difference between subjects had reduced when the two factors dealt with the same subjects, and the order of daytime and night-time medication was crossover and random.Continuous variables were expressed as the mean value plus or minus standard deviation (SD). The repeated measures engineered variance analysis was performed to achieve within-groups comparison and between-groups comparison. Paired t test was performed to compare between-groups at individual time points. A P value of <0.05 was considered statistically significant.Results: After medication during the day, arachidonic acid- induced platelet aggregation in the whole blood was highest at 10:00 when compared to values at 0:00, but these changes did not achieve statistical significance(P>0.05). After night-time medication, arachidonic acid- induced platelet aggregation was significantly highest at 20:00 when compared to values at 10:00(P<0.05). The changes did not achieve statistical significance when compared the average of platelet aggregation between two groups(P>0.05), but when compared two groups at individual time points, the study showed that arachidonic acid- induced platelet aggregation was significantly highest at 10:00 in day-time group when compared to values in night-time group(P <0.05).After medication during the day, ADP- induced platelet aggregation in the whole blood was highest at 10:00 when compared to values at 16:00 and after night-time medication, ADP- induced platelet aggregation was highest at 20:00 when compared to values at 10:00, but these changes did not achieve statistical significance(P>0.05). The changes did not achieve statistical significance when compared the average of platelet aggregation between two group(sP>0.05), but when compared two groups at individual time points, the study showed that ADP- induced platelet aggregation was significantly highest at 10:00 in day-time group when compared to values in night-time group(P<0.01).When compared the two inducers, ADP- induced platelet aggregation was significantly higher when compared with arachidonic acid- induced.Conclusions: There was a visual tendency towards differentiated diurnal platelet response to aspirin and clopidogrel. After taking aspirin during the day the platelet aggregation sharply increased during 6:00 ~ 10:00, and reached the peak at 10:00, then gradually declined in the bottom at 00:00 and showed a second peak during 16:00 ~ 20:00. After taking aspirin during the evening the platelet aggregation reached the peak at 20:00, then gradually declined in the bottom at 10:00 and these changes were significant. After taking clopidogrel during the day the platelet aggregation also reached the peak at 10:00, then declined in the bottom during 16:00 ~ 20:00 when the values appeared another increasing tendency. After taking clopidogrel during the evening the platelet aggregation reached the peak at 20:00, and then gradually declined in the bottom at 10:00. ADP- induced platelet aggregation was significantly higher when compared with arachidonic acid- induced, therefore clopidogrel also had inhibitory action for arachidonic acid- induced platelet aggregation .The difference was not obvious when compared the average of platelet aggregation between two groups, but after taking aspirin and clopidogrel during the evening the platelet aggregation at 10:00 was significantly lower than that of during the day, so this research indicated that taking aspirin and clopidogrel during the evening was superior to intaking during the day.
|
PDF Full Text Request