The Study On Gastrointestinal Prokinetic Agents Cisapride Induced Arrhythmia In Rats

Aim: Establish a model of cisapride producing cardiac arrhythmia to observe how cisapride affect the cardiac arrhythmia of rats. The HPLC method was used to determine the cisapride plasma concentration. Analyze the relationship between the effect of cisapride facilitating arrhythmia and its plasma concentration. In the present study the proarrhythmic potential of cisapride is a stoneturally elated drug, mosapride were compared.To explore the mechanism of cisapride facilitating arrhythmia.Methods: Spragne-Davley rats was selected and divided into four groups by randomizing method. Establish the case model of cisapride leading cardiac arrhythmia. The iv.dose range varied from 1.6 to 12.8mg/kg.The status was observed by electro— cardiograph. The HPLC method was used to determine the concentration of cisapride in kinds biology samples. Results: Cisapride could induce arrhythmia in rat.The incidence of arrhythmia was dose-dependent in the range from 1.6 to 12.8mg/kg, and 9.6mg/kg cisapride obviously decreased heart rate, the range from 405-378/min to 94-59/min in rat heart rate. The concentration of cisapride was determined by HPLC method. The method is accurate and reliable. It can satisfy the need of experiment. The incidence of arrhythmias is 62.5% at plasma concentration range of 12.14μg/ml. At 32.08μg/ml cardiac concentration of Cisapride could induce torsades de pointes(TDP), but plasma concentration of mosapride at 40.8μg/ml would not inducearrhythmias.Conclusion: We establish the case model of cisapride leading cardiac arrhythmia. Its can be fulfilled in experimental research. The effect of cisapride leading cardiac arrhythmia has apparent relationship with its cisapride concentration. Cisapride induce arrhythmia mechanism has relationship with its molecular structure.