维拉帕米逆转多器官功能衰竭犬心肌细胞电生理改变的机制研究  

Effects of verapamil on cellular electrophysiology in dogs with multiple organ dysfunction syndrome

作　　者：张玲[1] 宋建国[1] 李莉[1] 孙娟[1] 杨斌[1] 陈继红[1] 范平[1] 侯月梅[1] 

机构地区：[1]新疆医科大学第一附属医院心脏中心心律失常研究室,乌鲁木齐830054

出　　处：《中华心律失常学杂志》2010年第4期292-296,共5页Chinese Journal of Cardiac Arrhythmias

基　　金：国家自然科学基金（30760079）

摘　　要：目的探讨维拉帕米逆转72h多器官功能衰竭（MODS）犬的心肌细胞电生理改变作用机制。方法12只比格犬，平均体重（8．67±0．75）k，分成对照组（n=6）和MODS组（n=6）。酶解法分离72hMODS模型犬心室肌细胞，用膜片钳技术测定早期后除极（EAD），动作电位时限（APD）和L型钙电流（ICa-L），观察维拉帕米灌流前后EAD，APD和ICa-L的变化。结果MODS组的6只犬均出现窦性心律失常（窦性心动过速和窦性心律不齐）（100％；6of6，n=6），其中4只犬出现室性早搏（66％；4of6，n=6）。MODS组心室肌细胞出现显著的APD延长、ICa-L降低和易于诱发EAD等电生理改变。维拉帕米（100μmol／L）灌流后，显著降低钙电流，缩短延长的APD和消除EAD的诱发（100％；6of6，n=6），维拉帕米洗脱后，EAD可再次诱发（66％；4of6，n=6）。结论72hMODS心室肌细胞的APD显著延长、ICa-L降低和易于诱发EAD，维拉帕米可以降低钙电流、缩短MODS心室肌延长的APD和降低EAD的诱发率，提示维拉帕米在防治MODS犬早期心律失常的发生上可能有独到作用。Objective To investigate the possible mechanism of verapamil in reversing electrophysiological alterations in dogs with multiple organ dysfunction syndrome （MODS）. Methods Twelve dogs, weight （ 8.67 ± 0. 75 ） kg, were divided into control group （ n = 6 ） and MDOS group （ n = 6 ）. MODS was lasting for 72 hours. Ventricular myocytes were enzymatically isolated. Early afterdepolarizations （EAD）, action potential durations（APD） and L-type calcium currents were assessed before and after verapamil perfusion. Results Sinus arrhythmias in all MODS dogs （ 100% ;6 of 6, n = 6） and premature ventricular beats in 4 MODS dogs （66% ; 4 of 6, n = 6） were recorded, while no arrhythmias were observed in control animals. The prolongation of APD associated with decreased L-type Ca^2＋ currents and frequent provocation of EAD were the typical electrophysiological alterations in myocytes of MODS dogs. The APD prolongation was shortened, L-type calcium currents was decreased,and EAD was suppressed by using verapamil （ 100 μmol/L） in ventricular myocytes of MODS dogs （66% ;4 of 6, n = 6）. EAD could be induced after elusion of verapamil. Conclusions The cellular electro- physiological changes within 72 hours in the heart of MODS dogs were APD prolongation, markedly decreased L-type Ca^2＋ currents as well as frequently provoked EAD. Verapamil appears to be an effective agent in reversing the alternations of cellular electrophysiology in the early stage of MODS.

关 键 词：维拉帕米 多器官功能衰竭 动作电位时限 早期后除极 

分 类 号：R965[医药卫生—药理学] R459.7[医药卫生—药学]