普鲁卡因胺、利多卡因和普罗帕酮对豚鼠心室肌细胞Na^+/Ca^(2+)交换电流的抑制作用  

Direct inhibitory effects on Na^+ /Ca^(2+)exchange current of class Ⅰ antiarrhythmic agents procainamide,lidocaine and propafenone in isolated guinea pig ventricular myocytes

作　　者：吕吉元[1] 武冬梅[2] 李学文[1] 吴博威[3] 

机构地区：[1]山西医科大学第一医院心内科,太原030001 [2]山西医科大学第一医院基础医学院药理教研室,太原030001 [3]山西医科大学第一医院生理教研室,太原030001

出　　处：《中华心律失常学杂志》2003年第3期162-164,共3页Chinese Journal of Cardiac Arrhythmias

基　　金：山西省自然科学基金资助项目(19991078)

摘　　要：目的 利用膜片钳技术观察Ⅰ类抗心律失常药物普鲁卡因胺、利多卡因、普罗帕酮对Na^+/Ca^(2+)交换电流的直接作用。方法 采用胶原酶消化的成年大鼠单个心室肌细胞及全细胞膜片钳技术,记录Na^+/Ca^(2+)交换电流并观察药物对它的影响。结果 3种药物对Na^+/Ca^(2+)交换电流的抑制均呈剂量依赖性,但抑制程度不同,其中普鲁卡因胺抑制作用最强。50、100μM的普鲁卡因胺分别使外向Na^+/Ca^(2+)交换电流从对照值(181±22)pA降低至(125±19)、(109±20)pA,内向电流由对照值(172±18)pA分别降低至(137±13)、(121±12)pA;50、100μM的利多卡因使外向电流从对照值(170±15)pA分别降低至(139±15)、(127±10)pA,内向电流由对照值(165±15)pA分别降至(142±16)、(129±20)pA;50、100μM的普罗帕酮使外向电流由对照值(160±23)pA分别降至(130±27)、(112±26)pA,内向电流由对照值(169±13)pA分别降至(143±13)、(134±14)pA。普鲁卡因胺、普罗帕酮对外向电流的抑制大于内向电流,而利多卡因对内、外向电流的抑制差异无显著性。结论 Ⅰ类抗心律失常药物对心室肌细胞Na^+/Ca^(2+)交换电流具有直接抑制作用,且抑制程度不同。Objective To measure direct inhibitory effects of class Ⅰantiarrhythmic agents, procainamide, lidocaine and propafenone on Na+ /Ca2+ exchange current. Mefliods Using whole-patch clamp configuration in iso-lated guinea pig ventricular myocytes with an enzymatic procedure, Na+/Ca exchange current were measured be-fore and after application of each drug respectively. Results All of the three drugs concentration-dependently inhibited Na+ /Ca + exchange current, but there were different degrees of inhibition among them. The effect of procainamide was the most potent one . At concentration of 50, 100 μM, procainamide decreased oubvard INa+/Ca2+ from control (181 ± 22)pA to (125 ± 19) , (109 ± 20)pA , respectively, and decreased inward INa+Vca2+ from (172 ± 18)pA to (137 ± 13) , (121 ± 12)pA, respectively. Lidocaine inhibited outward INa+/Ca2+ from (170 ± 15)pA to (139 ±15), (127±10)pA, and inhibited inward INa+/Ca2+ from (165 ± 15)to (142 ± 16), (129±20)pA, respectively. Propafenone inhibited outward INa+/Ca2 + from (160 ±23)pA to (130 ±27), (112±26)pA, inward INa+ /Ca2+ from (169 ± 13)pA to (143 ± 13), (134± 14)pA, respectively. Procainamide and propafenone showed more sigificant inhibition on outward INa+/Ca2 + than on inward INa+/Ca2+ , while lidocaine's effect on both outward and inward INa+/Ca2+ was similar. Conclusion Class Ⅰ antiarrhythmic agents have direct inhibitory effects on Na+/Ca2+ ex-change current in isolated guinea pig ventricular myocytes, and the extents of effect are different among drugs.

关 键 词：抗心律失常药物 普鲁卡因胺 利多卡因 普罗帕酮 心室肌细胞 Na^+/Ca^2+交换电流 

分 类 号：R541[医药卫生—心血管疾病]