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Objective@#To analyze association of CYP2C19 genotype and platelet function phenotype and their impact on clinical outcomes including bleeding events of coronary artery disease(CAD) patients received clopidogrel post percutaneous coronary intervention(PCI).@*Methods@#Coronary atherosclerotic heart diseases patients underwent elective PCI and coronary stent implantation in Fuwai hospital were prospectively enrolled during May 2012 to April 2013. Patients were assigned into groups by genotype of CYP2C19 (extensive metabolizers, intermediate metabolizers, and poor metabolizers) and phenotype of platelet function (clopidogrel responders, semi-responders, and non-responders). The rates of major adverse cardiovascular events, combined cardiovascular events, and bleeding events were recorded during a at least 12 months follow-up period and compared among above defined groups. The association between genotype or phenotype and clinical outcome was assessed using multivariable Cox regression hazards model.@*Results@#Three hundred and eighty patients received coronary stent implantation and met the inclusion criteria of the study, including 157(41.3%) clopidogrel extensive metabolizers, 176(46.3%) intermediate metabolizers, and 47(12.4%) poor metabolizers according to the genotype grouping; 98(25.8%) were responders to clopidogrel, 149(39.2%) were semi-responders, and 133 (35.0%) were non-responders according to the phenotype grouping. Three hundred and seventy-six patients accomplished follow-up. The highest combined cardiovascular events rate was observed in the poor metabolizers (34.0%(16/47)) as compared to the intermediate metabolizers (19.0%(33/174), P=0.026) and the extensive metabolizers (15.5%(24/155), P=0.005). The highest bleeding events rate was observed in the clopidogrel responders (33.7%(33/98)) as compared to the semi-responders (18.9%(28/149), P=0.008) and non-responders (17.7%(23/130), P=0.008). In multivariable Cox regression analysis, the adjusted risk of cardiovascular death, acute myocardial infarction, stent embolism, target lesion revascularization and angina onset was 2.305 times higher in clopidogrel poor metabolizers than in extensive and semi-metabolizers (95%CI=1.208-4.399, P=0.011). The adjusted HR for bleeding events was 0.540 (95%CI=0.321-0.909, P=0.021) among semi-responders vs. responders, was 0.52 (95%CI=0.301-0.905, P=0.021) among non-responders vs. responders during the 12 months follow-up period.@*Conclusions@#Among CAD patients underwent stenting and clopidogrel treatment, poor CYP2C19 metabolizers group carries a significantly higher risk for combined cardiovascular events than in extensive metabolizers group, while clopidogrel responders patients are at significantly higher risk for bleeding as compared to the semi-responders and non-responders.
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Objective Routine perioperative intravenous antimicrobial agents,was administered as surgical prophylaxis.However,whether balanced ultrafiltration during extracorporeal circulation can remove antimicrobial agent remains unclear.The concentrations of antimicrobial agent in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model.Methods Extracorporeal circulation consisted of cardiotomy reservoir (Ningbo Fly Medical Healthcare CO.,LTD.Ningbo,China),D902 Lilliput 2 membrane oxygenator (Sorin Group Asia Pte Ltd,Beijing,China) and Capiox (R) AF02 pediatric arterial line filter (Terumo Corporation,Beijing,China).HEMOCONCENTRATOR BC 20 plus (MAQUET Cardiopulmonary AG,Hirrlingen,Germany) was placed between arterial purge line and oxygenator venous reservoir.Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24％-28 ％.After 30 minutes of extracorporeal circulation,zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mm Hg(1 mm Hg =0.133 kPa) with Hoffman clamp.The rate of ultrafiltration (12 ml/min) was controlled by ultrafiltrate outlet pressure.Identical volume of plasmaslyte A was dripped into the circuit to maintain stable hematocrit during 45 minutes of experiment.Plasma and ultrafiltrate samples were drawn every 5 minutes and concentrations of antimicrobial agent (including Cefmetasole and cefotiam) were measured with high performance liquid chromatography.Results All these two antimicrobial agents were detected in ultrafiltrate,demonstrating hemoconcentration may remove antimicrobial agent.The concentration of plasma antimicrobial agent decreased lineally with the increase of ultrafiltrate volume.At end of balanced ultrafiltration,the concentration of plasma cefotiam was (104.96 ± 44.36) μg/ml,which is about (44.38 ± 7.42) ％ of the initial concentration (238.95 ± 101.12) μg/ml; the concentration of plasma cefmetazole decreased linearly to (25.76 ± 14.78) μg/ml,which is about (49.69 ± 10.49) ％ of the initial concentration (51.49 ± 28.03) μg/ml.The total amount of cefotiam in ultrafiltrate is (27.16 ± 12.17)％ of the total dose administered,whereas cefmetasole in ultrafiltrate is (7.74 ±4.17)％.Conclusion Balanced ultrafiltration may remove antimicrobial agent from serum and has significant influence on plasma concentration of antimicrobial agent.The strategy of surgical prophylaxis should consider this unique technique during extracorporeal circulation.