Anticoagulants are recommended for the prevention and treatment of a wide variety of thromboembolic events.Although existing anticoagulants are effective,their usage is limited by parenteral administration or the requirement for frequent monitoring and subsequent dose adjustment.Therefore,there is an urgent need for novel,oral agents with a predictable anticoagulant action.Because of its key position in the coagulation cascade and its limited roles outside of coagulation,Factor Xa has presented as an attractive target for novel anticoagulants.As a result,the past decade has witnessed an explosion of research into small-molecule,oral,direct Factor Xa inhibitors,and some are now in clinical development.Rivaroxaban is currently furthest ahead in its developmental program,having entered phase III in 3 indications.It is hoped that,before long,these anticoagulants will allow us to enter an era of convenient,oral anticoagulation,without the need for regular monitoring or dose adjustment.

The cardiovascular ion channel disease is one of the main among ion channel diseases.It plays the important effect of cardiovascular disease.Ion channel diseases are responsible for almost all arrhythmias and sudden cardiac death.This text reviews genetic and acquired cardiac ion channel diseases,and associated treatments are introduced briefly.

Percutaneous coronary intervention(PCI) has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s.Bare-metal stents and,more recently,first-generation drug-eluting stents(DES),such as sirolimus-eluting(Cypher) and paclitaxel-eluting stents(Taxus),have further improved results of percutaneous coronary intervention by improving early results and reducing the risk of restenosis.There are currently debates on the safety of these first-generation DES,given the potential for late stent thrombosis which is a first-generation drug-eluting stent of the largest security issue,especially after discontinuation of dual antiplatelet therapy.Next-generation DES such as everolimus-eluting stents(Xience V) holds the promise of superior anti-restenosis efficacy as well as long-term safety.This review makes a presentation of the evidence-based clinical research according to everolimus-eluting stents(Xience Ⅴ).

AIM: To evaluate the effects of different doses of valsartan alone or with concomitant benazepril on blood pressure, left ventricular hypertrophy, RAAS function and endoxin level in spontaneously hypertensive rats (SHR). METHODS: Thirty SHR (fourteen-week-old, male) were divided into five groups (six rats in each group ): SHR control group: fed with normal saline; benazepril group: fed with 1 mg?kg -1 ?d -1 benazepril); low dose valsartan group: fed with 8 mg?kg -1 ?d -1 valsartan ; high dose valsartan group: fed with 24 mg?kg -1 ?d -1 valsartan ; combination drug therapy group: fed with valsartan (8 mg?kg -1 ?d -1 ) and benazepril (1 mg?kg -1 ?d -1 ), all for 8 weeks. WKY control group (n=6):fed with normal saline for 8 weeks.RESULTS: SBP, LVM/BW,TDM of SHR were remarkably lower than those of control after drug intervene, and effect on SBP was most remarkable in high dose valsartan group and in the combination drug therapy group; effect on LVM/BW,TDM were most remarkable in combination drug therapy group. Renin activities in plasma and myocardium were remarkably increased in drug intervene groups. The levels of Ang Ⅱ in plasma and myocardium were remarkably increased in two different dose of valsartan treating group, and the larger dose of valsartan were, the higher levels of Ang Ⅱ in plasma and myocardium were; decreased in benazepril treating group and combination drug therapy group. Na +-K +-ATPase activities in myocardium were remarkably increased and the level of endoxin in myocardium were remarkably decreased as SBP decreased after drug intervene. CONCLUSION: Different dose of valsartan alone or combined with benazepril can decrease SBP of SHR, have the effect of inhibiting progression of ventricular hypertrophy. The effect of combination drug therapy group was most remarkable among five groups and can avoid the side effect of high AngⅡ in plasma and myocardium during long-term use of valsartan alone.

AIM To evaluate the changes of serum and brain tissue endoxin in model of bilateral cerebral hemisphere ischemic reperfusion injury, and effect of anti digoxin antiserum (an antagonist of endoxin). METHODS The bilateral cerebral hemisphere ischemic model was prepared by ligating three vascular by Kameyama's manner. SD rats were randomly divided into 7 groups and each group had 8 rats. Sham group, ischemic reperfusion group, negative control group, nimodipine group, low concentration anti digoxin antiserum group, middle concentration anti digoxin antiserum group, high concentration anti digoxin antiserum group. The blood was collected at the end of reperfusion, meanwhile rats were killed, and the bilateral cerebral hemisphere were took out and used to prepare encephlon homogenate and made into samples of light microscope. RESULTS Compared with sham group, the serum CK content increased; Brain tissue SOD activity reduced and MDA content increased importantly in ischemia reperfusion group; The levels of serum and brain tissue endoxin in ischemia reperfusion group were significantly higher, while ATPase activity in brain tissue decreased; Mitochondrial Ca 2+ content in brain tissue increased significantly and Mg 2+ content decreased significantly. In brain tissue,there was some inflammatory change and local necrosis;The rank order and structure of cell wasn't clear;The morphology of pyramidal cell was abnormal. Compared with ischemic reperfusion group, Anti digoxin antiserum reduced serum CK content; It antagonized lowering of SOD activity and increase of MDA content in brain tissue; It remarkably reduced the level of brain tissue endoxin; It reduced abnormal ion content of brain tissue mitochondrion induced by cerebral ischemic reperfusion injury; The high and middle concentration anti digoxin antiserum had a significant effect on raising brain tissue ATPase activity. It reduced neuron denaturation. CONCLUSION Cerebral ischemic reperfusion can increase the level of brain tissue and serum endoxin and higher endoxin can promote brain injury. Endoxin is a major factor involved in cerebral ischemic reperfusion injury. Anti digoxin antiserum can reduce brain tissue injury and had a protective and treatment effect on cerebral ischemic reperfusion injury by antagonizing the effect of endoxin.

To evaluate the protective effect of anti-digoxin antiserum on hypoxic injury myocardium and its mechanism.Methods It was observed that different concentration anti-digoxin antiserum effect on endogenous digitalis-like factor and cell membrane ATPase activity in hypoxic myocardium model.Results The level of endogenous digitalis-like factor was remarkably higher,cell membrane ATPase activity were remarkably lower in hypoxic group than those of normal group;anti-digoxin antiserum can resume membrane ATPase activity.Conclusion Rise of endogenous digitalis-like factor was basic of molecular biology of myocardial damage during myocardial hypoxia.Anti-digoxin antiserum has lightened myocardial injury and has protective effect on hypoxic myocardium by against effect of endogenous digitalis-like factor.

AIM: To evaluate the antagonistic effect of anti - digoxin antiserum on hypoxic myocardium and its mechanism. METHODS: It was observed that different concentration of anti-digoxin antiserum effect on endoxin and cell membrane ATPase activity in hypoxic myocardium model. RESULTS: The endoxin level was much higher, cell membrane ATPase activity was much lower in hypoxic myocedium than those of noed; anti-digoxin antiserum can resume membrane ATPase activity. CONCLUSION: Rise of endoxin was basic in molecular biology of myocar- dial damage during myocardial hypoxia. Anti - digoxin antiserum decreased myocardial damge and has protective ef- fect on hypoxic myocardium by antagonistic effeCt of endoxin.

AIM: To observe the effect of endoxin antagonist,anti-digoxin antiserum,on endoxin level,ATPase activities,intramitochondrial total calcium concentration and gene expression of sodium pump isoforms in myocardium of rats with myocardial ischemia reperfusion(MIR).METHODS: Fifty-six male Sprauge Dawley rats were randomly divided into 7 groups.Sham operation group: silk suture threading the left anterior descending coronary artery without ligature;MIR group: left anterior descending coronary artery was subjected to 30 min ligation followed by 45 min reperfusion;normal saline group: MIR model was given 5 mL/kg normal saline;verapamil group: MIR model was given 5 mg/kg verapamil;low dose antidigoxin antiserum group: MIR model was given 8.6 mg/kg antidigoxin antiserum;middle dose antidigoxin antiserum group: MIR model was given 17.3 mg/kg antidigoxin antiserum;high dose antidigoxin antiserum group: MIR model was given 34.5 mg/kg antidigoxin antiserum.All drugs were injected into vessel via femoral vein within 5 min before reperfusion,respectively.After reperfusion,left ventricle myocardium samples were processed immediately in order to measure the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase,endoxin level,intramitochondrial total calcium concentration and the experssion of ?1,?2,?3 and ?1 isoforms of sodium pump on mRNA and protein levels by RT-PCR and Western blotting and immunohistochemical assay,respectively.RESULTS: After MIR,the level of endoxin in myocardium was obviously increased.The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in myocardial membrane were significantly decreased while intramitochondrial total calcium concentration increased.The gene expression of the ?1,?2,?3 and ?1 isoforms of sodium pump at both mRNA and protein levels were reduced markedly.Only the effect of verapamil on reducing intramitochondrial total calcium concentration was observed.Antidigoxin antiserum significantly reduced the level of endoxin in myocardium,restored the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase,reduced intramitochondrial total calcium concentration,and up-regulated the expression of ?1,?2,?3 and ?1 isoforms of sodium pump at both mRNA and protein levels.CONCLUSION: MIR results in increase of endoxin secretion.The latter depresses the activity of Na+-K+-ATPase by down-regulating the gene expression of ?1,?2,?3 and ?1 isoforms of sodium pump in myocardial membrane,and also induces intramitochondrial calcium overload,thereby mediates MIR injury.

The determination of serum endogenous digitalis-like factor concentrations ( SEDFC ) and serum digoxin concentrations ( SDC ) was carried out in 30 patients with chronic pulmonary heart disease ( CPHD ) with radio immunoassay. The results showed that(1) the SEDFC in patients with CPHD were significantly lower than those of normal cases, P

Aim To research the changes of myocardial endoxin level in rats with myocardial ischemia reperfusion (MIR) and the protevtive effects of anti digoxin antiserum, an endoxin specific antagonist, on MIR injury. Methods Myocardial ischemia reperfusion injury models were obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprauge Dawley rats were randomly divided into seven groups each with 10 rats. There were sham group, MIR group, normal saline group, verapamil group, low dose anti digoxin antiserum group, middle dose anti digoxin antiserum group, and high dose anti digoxin antiserum group. After reperfusion of left ventricular myocardium, sample of ischemia were processed immediately. Myocardial endoxin levels, Na +, K + ATPase activities, and intramitochondrial Ca 2+ contents were measured. The myocardial morphology were observed. Results Myocardial endoxin levels were significantly increased; Na +, K + ATPase activities were remarkably decreased; intramitochondrial Ca 2+ contents were remarkably raised. Meanwhile, myocardial morphology injury were remarkable in light microscope and electric microscope. Middle and high dose of anti digoxin antiserum intervention, myocardial endoxin levels were remarkably decreased; Na +, K + ATPase activities were drastically increased; intramitochondrial Ca 2+ declined. The myocardial histological morphology was significantly improved. Conclusion Antidigoxin antiserum, an endoxin antagonist, had protective effect against MIR. The mechanism maybe related to antagonizing endoxin, restoring energy metabolism, attenuating intracellular Ca 2+ overload.