The Study On Improvement Of Fasudil On The No-reflow Or Slow-flow In Direct PCI Surgery After STEMI

Background: Large clinical trials have confirmed that in acute ST-segmentelevation myocardial infarction dysfunction, ischemia reperfusion injury is one of themechanisms of myocardial microcirculation (slow flow or no reflow), and oxidativestress is the main factor of the occurrence and development. Oxidative stress has avariety of related indicators, such as superoxide dismutase (SOD), serum type oxidizedlow density lipoprotein (ox-LDL), malondialdehyde (MDA), etc.With the risingindicence of acute myocardial infarction and the increasing cases of interventionaltreatment of coronary heart disease in our country, adverse cardiovascular events causedby myocardial microcirculation disorder have been brought into focus.A large body ofresearch has been carrzed out the myocardial microcirculation. Traditional drugs such asverapamil[1], adenosine[2-3], sodium nitroprusside[4]and abciximab can partially reverse no-reflow, but the increased risk of bleeding and negative inotropic effect have limited theclinical application. Therefore,it is an important research topic to look for safe andeffective alternative medicine.Recent studies have provided a deeper insight into therole of the Rho/ROCK pathway in cardiovascular disease.Now,several Rho kinaseinhibitors have been development.Among them fasudil is currently the most commonyused with sufficient evidence in clinical trials.Fasudil can inhibit oxidative stress andthus relieve ischemia-reperfusion injury.But whether fasudil can improve themyocardial microcirculation of ASTEMI patients (no reflow or slow blood flow) duringPCI in remains to be confirmed.Objective:To eyaluate the effect of fasudil on the microcirculation dysfunction (noreflow or slow blood flow)during direct PCI for ASTEMI patients.Methods: The subjects were selected from the hospitalized patients with STEMI(diagnosed according to the ACC/AHA2010guidelines).They all received directpercutaneous coronary internetion and had no reflow or slow blood flow phenomenonduring the procedure from January2011to December2012.They were randomized into groups,Group A and Group B. The subjects in Group A received fasudil (injectedthrough the micro catheter into the coronary arteries at4mg/20ml/3min). The patients inGroup B received verapamil(injected through the micro catheter into the coronaryarteries at0.5mg/20ml/3min). The clinical features, distribution of coronary arterylesions,myocardial blush grades （MBG）,ST-segmen（tSTR,＞70%）24hour after thepercutaneous coronary internetion, the levels of superoxide dismutase before and isminutes after drug infusion and the safety indicators were observed in the two groups.Results:1.86patients are selected, Group A:45cases, mean age67.06±12.9years,male/female ratio25:20；Group B:41cases, mean age65.87±9.53years, male/femaleratio25:16. There was no difference in the follow aspects on the baseline between twogroups: Age, sex ratio, risk factors for coronary heart disease, distribution of coronaryartery lesions frame the severity of the coronary artery lesions and the time of theinterventional procedure, P﹥0.05.2. MBG grade in Group A improved sighficantly compared with that in Group B(2.10±0.11vs.1.50±0.13, P=0.003); the percentage of24h-STR in Group A also exceedsthat in Group B(68%vs.45%, P=0.004).3. There was no difference in the level of superoxide dismutase before druginfusion between the two groups,(P=0.45).15min after drug infusion,the level of SODin Group A rised from375.31±55.07to524.93±57.67pg/ml, P﹤0.01And in Group B itincreased from382.61±55.28pg/ml to529.21±56.30pg/ml,(P﹤0.01). The increase inSOD in Group A was higher than that in Group B, and the difference was statisticallydifferent(P﹤0.05)4. Safety assessment: the mean arterial pressure of the two groups before druginjection were92.24±24.36mmHg and88.92±19.85mmHg,(P=0.536); The meanheart rate was67.35±14.35beats/minute in Group A and it was70.55±16.44beats/minute in Group B,(P=0.12).With in3minutes after drug injection,transient mildblood pressure coourred in Group A.Hear Rate did not vary significantly.And there isno significant difference in BP berfe after drug injection.In Group B,low blood pressureoccurred rapidly after drug injection and persisted at a relatively low lever.Thepercentage of subjects who needed dopamine were significantly higher than that inGroup A(34.67%vs62.36%. P﹤0.05).Inaddition,subjects in Group B had siower heartrate immediately,and the percentage of temporary pacemaker were remarkable higher than that in Group A(23.67%vs74.65%, P﹤0.05).Conclusion: The condition of no-reflow or slow-flow during direct PCI forSTEMI patients was improved after intra coronary drug injection.Compared betweenthe two groups,the efficacy of fasudil is superior to that of verapamil.Fasudil,as a novelvasodilation, can be used to treat the no-reflow or slow-flow in PCI for STEMIpatients,and relieve myocardial microcirculation dysfunction.