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 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.

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: Changes of endoxin level, ATPase activities, intramitochondrial Ca2+ concentration, and gene expression of Na+-K+-ATPase isoforms in myocardium of rats with MIR and effect of verapamil were observed, in order to investigate mechanism of endoxin mediating intracellular calcium overload of myocytes. METHODS: Twenty four male Sprauge Dawley rats were randomized into 3 groups. Sham operation group: silk suture was threaded the left anterior descending coronary artery without ligature; MIR group (MIR): left anterior descending coronary artery was subjected to 30 min ligation followed by 45 min reperfusion; verapamil group: MIR model was given 5 mg/kg verapamil. Verapamil was injected via femoral vein 5 min before reperfusion. Left ventricle myocardium samples were processed immediately after reperfusion in order to measure the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase, endoxin level, and intramitochondrial Ca2+ concentration. The levels of ?1, ?2, ?3 and ?1 isoforms of Na+-K+-ATPase were measured by immunohistochemical assay. RESULTS: After MIR, the level of endoxin in myocardium was substantially increased; the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in myocardial membrane were significantly decreased while the concentration of intramitochondrial Ca2+ was increased; the levels of the ?1, ?2, ?3 and ?1 isoforms of Na+-K+-ATPase were reduced markedly. Verapamil had only effect on reducing the concentration of intramitochondrial Ca2+. CONCLUSION: MIR increases endoxin secretion. The latter may depress the activity of Na+-K+-ATPase by changing the gene expression of ?1, ?2, ?3 and ?1 isoforms of Na+-K+-ATPase in myocardial membrane, inducing intramitochondrial Ca2+ overload.

Aim To investigate effects and the mechanism of endoxin special antagonist anti-digoxin antiserum on heart function in myocardial anoxia-reoxygenation injury in rats. Methods The isolated Langendorff perfused rat heart model was established. Sixty Sprague Dawley(SD) rats were randomly divided intosix groups and each group had 10 rats: control group, anoxia-reoxygenation group, verapamil group, low, middle, high dose anti-digoxin antiserum groups. ECG, HR, LVDP and ?dp/dtmax were continuously recorded. The endoxin levels and intramitochondrial Ca2+ contents in myocardial tissues and nitric oxide (NO) contents in coronary artery fluence were measured after reoxygenation. Structures of mitochondrial and endothelial cells were observed by microscope. Results The anoxia-reoxygenation group showed a remarkable increase in endoxin level and intramitochondrial Ca2+ content, an obvious decrease NO content, an obvious injury of mitochondrial and endothelial cell, an obvious inhibition of heart function. Middle, high dose of anti-digoxin antiserum group could remarkably decrease endoxin level and intramitochondrial Ca2+ content; increase NO content; obviously relieve the injury of mitochondrial and endothelial cells; remarkably improve the discovery of heart function. Conclusion Anti-digoxin antiserum could inhibit the failure of heart function induced by myocardial anoxia-reoxygenation injury. Its mechanism may be related to antagonize endoxin, relieve mitochondrial Ca2+ overload, increase NO contents, and protect the function of mitochondrial and endothelial cells.