Quinidine's Effect For Electrophysiological Characteristics Of Transient Outward Potassium Current Related To Sudden Cardiac Death

Background: Among the cause of sudden death, sudden cardiac death(SCD) can account for 80 percent of them. However, it is the only implantable cardioverter defibrillator (ICD) that can play therapeutic effect for SCD now. But ICD cannot prevent beforehand ventricular tachycardia(VT), so it is very necessary to further study the mechanism of SCD. We adopt transient outward potassium current (Ito1) of the ventricular cells in the rats as the object of the topic. Because of in the nonorganic heart disease (NOHDA) population represented by 'Brugada syndrome', Itol plays an important role for mechanism of SCD in them.At the same time, as the most of SCD population----the patient of acute myocardial infarction(AMI), if revascularization can improve myocardium heterogeneity and reduce incidence of SCD,it has important meaning to study the macroscopic index which reflect heterogeneity of Itol in myocardium.Objective: To study electrophysiological characteristics of Itol in ventricular myocardial cells of normal rats, including current intensity, kinesics of activation, deactivation, recovery and voltage dependence , frequency dependence. At the same time, to observe theeffects of quinidine and 4-Aminopyridine for Itol.and to approach the mechanism of quinidine's active effect for 'Brugada syndrome' in ionic deck.On the other hand, for the acute myocardiac infarction (AMI) subjects, there exists the theory that electrical heterogeneity is mainly caused by Itol heterogeneity, and mechanism of SCD is mainly caused by electrical heterogeneity. Through revascularization recovering electrical heterogeneity and follow-up incidence rate of SCD in AMI, let us to learn the relationship between myocardium involved by MI and electrical heterogeneity.Methods: Single ventricular cells of normal rats was obtained by an enzymatic dissociation method. Whole cell patch clamp technique was used to record Itol, following the administration of quinidine and 4-Aminopyridine,we observe the electrophysiological characteristics of Itol and effect of quinidine and 4-Aminopyridine on it.In clinic aspects: we analysised 102 cases AMI patients from 1999 .1 . to 2003.2 .for accepted hospitalization, disguishing them in three groups, they are LVEF < 40%(n=15), 40% < LVEF < 50%(n=12) , LVEF > 50%(n=75) groups, respectively. They are to be followed in incidence of SCD from one year to four years.Result: 1 ? There existed potent Itol in rat ventricular myocardial cells; (D Along with stepping up of membrane voltage, Itol intensity and density also increase; (D The curve of Itol's activation and deactivation take on S model and inverse S model, respectively. They can both be fitted by Boltzmann equations; ?.the characteristic of frequency dependence of Itol.2 ? There existed potent inhibit effect of 'quinidine' and'4-Aminopyridine' for the average peak Itol current intensity; P < 0.05.CD .The characteristic of concentration dependence of Itol.. d> theinhibition effect of quinidine also take on voltage dependent.? Through quinide's effect, the curve of Itol's activation and deactivation can both fitted by Boltzmann equations, the activation curve move right. P > 0.05. ? The curve of the time recovery move right in the use of quinidine ,it can be fitted by Boltzmann equation .? The inhibitory action of quinidin increase along with stimulation frequency increase. But '4-aminopyridine' 's effect take on 'inverse frequency dependent'.3 In clinic aspects: during the follow up 1 ~ 4 years. 8 of 102 instances suffered SCD. LVEF < 40% groups has 4 cases ,26.7% . 40% < LVEF<50% has 1 case ,8.3%, LVEF > 50% has 3cases, 4%.. the SCD rate of LVEF < 40% groups is higher than other groups significance difference. Other two groups are not significance difference.To use multivariable Logistic regression, the risk factors of the population of takeing place SCD are: LVEF < 40%, ages, multi-branch process. Their odds ratio and 95% confidence interval are:LVEF < 40%groups: 3.221 and 0.772 - 3.429,respectively; ages: 2.291 and 0.458 - 1.473,respectively; multi-branch process: 1.025 and 0.731-1.437,respectively.Conclusion: 1 (D There exists potent Itol in rat left ventricular cells, it is in charge of repolarization 1 stage 'peak - dome' action potential(AP). ? The peak of Itol can be supressed by quinidine, these effect are interfered by time recovery dynamics after deactivation course of Itol. (D quinidine inhibit Itol and lengthen time course of AP, which may be one of important role as treating 'Brugada syndrome' . Equally '4-aminopyridine' inhibit Itol and affect electrical heterogeneity, due to lacking of defecting clinic data, so it still remain the instrument drug level.2 For AMI Patients accepted revascularization, the risk factor affecting SCD incidence rate are left ventricular funtion, multi-branch precoss> age. According to the theory, that MI enlarging electricalheterogeneity in 'infarct region' and 'non-infraction region' mainly because of change of Itol. 'Myocardium .involved' and 'electrical heterogeneity' show correlativity after ML.More are myocardium involved, lower are LVEF, more obviously are ' electrical heterogeneity, higher are SCD incidence rate ; multi-branch precoss's effect for 'electrical heterogeneity' is to make 'electrical heterogeneity' happen in more region, leading to SCD incidience higher. We may make left ventricular function and multi-branch process as detecting level of microelectrical heterogeneityd to macrotarget, as the indicatio of this type of revasculariaton populationis. In order to reduce SCD, further development should be full 'revasculariaton' .