Effects Of AMP579 And Adenosine On Expression Of IL-18 And Platelet Aggregation In Patients Blood With Coronary Heart Disease

Objective:AMP579 is a novel adenosine agonist with a long half-life period.Administration of AMP579 prior to or during myocardial ischemia significantly reduces infarct size in rabbit and pig,showing its stronger cardioprotective effect than adenosine dose.So far,however,no reports about the effects of AMP579 to the secretion of IL-18 in patients blood with coronary heart disease(CHD)could be found.The aim of my study is to observe the effects of AMP579 on secretion of IL-18 in patients blood with CHD;to compare the effects with adenosine in the same condition.This study will benefit to explore the IL-18 mechanisms underlying the cardioprotective effect of AMP579 and to predict its utility in treatment of CHD.Methods:The patients(15 patients with acute myocardial infarction diagnosed by clinical symptoms,changes of elereocardio-gram and myocardial biochemical markers,15 patients with unstable angina pectoris)and 15 normal individuals were drew blood and every blood sample was divided to eight groups—control(n=15),A1(AMP579,10μmol·L^-1),A2 (AMP579,30μmol·L^-1),A3(AMP579,100μmol·L^-1),A4(AMP579,300μmol.L^-1)and B1(Ado,30μmol·L^-1),B2(Ado,100μmol·L^-1),B3(Ado,300μmol·L^-1),B4(Ado,1mmol·L^-1).A1, A2,A3,A4 were incubed AMP579 respectively,B1,B2,B3,B4 were incubed adenosine respectively.The expression of IL-18 on monocytes were measured by ELISA.Platelet aggregation was measured using turbidimetric method.Results:Expression of IL-18 on monocytes in CHD patients were markedly higher than those in normal cases(p＜0.0001),and expression of IL-18 in AMI and UAP were not significantly different(p＞0.05).Compared with control groups,adenosine(30μmol·L^-1,100μmol·L^-1, 300μmol·L^-1)remarkably enhanced expression of IL-18 in AMI and UAP,AMP579 (10μmol·L^-1,30μmol·L^-1,100μmol·L^-1)remarkably reduced expression of IL-18 in AMI and UAP.But adenosine(1mmol·L^-1)remarkably reduced expression of IL-18 in AMI and UAP, AMP579(300μmol·L^-1)remarkably reduced expression of IL-18 in AMI and UAP.Platelet aggregation induced by epinephrine was significantly heightened,in patients with CHD than those in healthy adults;Compared with control groups,adenosine and AMP579 (10μmol·L^-1,30μmol·L^-1,100μmol·L^-1)remarkably inhibited Platelet aggregation triggered by epinephrine.But Platelet aggregation in adenosine and in AMP579 were not significantly different in the same condition(p＞0.05).Conclusions:Expression of IL-18 in the CHD patients was markedly higher than those in normal cases.AMP579 and adenosine differentially regulates expression of IL-18 through several subtypes of adenosine receptors.AMP579 shows a more powerful effect than adenosine dose on receptor affinity,which is favorable to reduce drug dosage.AMP579 and adenosine could dose-dependently inhibit platelet aggregation in healthy adults and CHD patients. AMP579 has similar inhibitory effect on platelet aggregation compared with adenosine in the same condition.