Investigating The Electrophysiologic Effects Of Dofetilide On FPs Of Cultured Myocytes By Microelectrode Arrays

AIM:To investigate the morphologic characteristics of field potentials(FPs)of cultured ventricular myocytes,and analyse the effects of Dofetilide in different concentration on FPs of cultured ventricular myocytes of suckling mice by microelectrode arrays(MEAs).METHODS:The preparations of cultured ventricular myocytes with spontaneous impulse which placed in MEAs pads were obtained by the technique of primary myocardial cell culture.FPs recordings by means of MEAs were performed to investigate the electrophysiologic properties of cultured ventricular myocytes of suckling mice.There are three groups which performed in our research:control group(n=20), 0.01μmol/L Dofetilide group(n=20)and 1μmol/L Amiodarone group(n=20).In order to investigate the effects of Dofetilide in different concentration,control group(n=10), 0.005μmol/L Dofetilide group(n=10),0.01μmol/L Dofetilide group(n=10),0.1μmol/L Dofetilide group(n=10)and 1μmol/L Dofetilide group(n=10)were also performed in our research.We record cultured ventricular myocytes' FPs and observe both FPdur and impulse rate by MEAs.RESULTS:Our result shows that FPdur prolongation and impulse rate decrease can be observed both in Dofetilide(0.01μmol/L)group and Amiodarone(1μmol/L)group(FPdur:F=271.549,P＜0.01.Impulse rate:F=75.690, P＜0.01).Compared with the control group,FPdur prolongation and impulse rate decrease become more and more conspicuous by using Dofetilide from concentration of 0.005μmol/L to 1μmol/L(FPdur:F=124.610,P＜0.01.Impulse rate:F=50.340,P＜0.01). CONCLUSION:Dofetilide presents its antiarrhythmic function by prolonging FPdur as Amiodarone.FPdur prolongation shows a concentration gradient effect by using Dofetilide from concentration of 0.005μmol/L to 1μmol/L on cultured ventricular myocytes of suckling mice.It is effective and safe for cultured ventricular myocytes of suckling mice by using Dofetilide in dosage of 0.01μmol/L.The risk of proarrhythmia can be increased by using Dofetilide in concentration beyond 0.01μmol/L.Therefore, MEAs mapping technique offers a versatile and powerful platform to study the concentration gradient effects of drugs and the proarrhythmic effects of antiarrhythmic drugs.Additionally,the combination of preparations for cultured ventricular myocytes with the MEAs technique provides a novel technology to study both electrical activity of multicellular preparations of functional defective cardiac tissues and the effects of related drugs.