Wang Jun-Kui, Cui Chang-Cong, Zhang Hong, Yao Qing-Hai, Yao Xiao-Wei, Chen Xin-Yi
Department of Cardiology, First Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Sheng Li Xue Bao. 2004 Aug 25;56(4):487-92.
Experiments were performed to investigate the effects of long-term treatment with adrenergic receptor antagonist on electrical remodeling of the left ventricle with chronic pressure-overload. New Zealand rabbits underwent subtotal banding of superrenal abdominal aorta. At 10 weeks after surgery, echocardiography examination was performed, then action potential (AP), inward rectifier potassium current (I(Ki)), delayed rectifier potassium current (I(K)) and Na(+)/Ca(2+) exchanger current (I(Na(+)/Ca(2+))) were recorded in midmyocardial cells isolated from left ventricle of abdominal aorta banded group (banded group), abdominal aorta banding plus Carvedilol intervention group (Carvedilol group), and normal control group rabbits by using the whole-cell patch-clamp techniques. The results showed that left ventricular mass index in control, banded, and Carvedilol groups were 1.78+/-0.06 (n=7), 2.33+/-0.11 (n=7), and 1.87+/-0.08 (n=7), respectively (banded vs control and Carvedilol, P<0.01). At basic cycle length of 2 s, AP duration (measured at 90% repolarization, APD(90), ms) in control, banded, and Carvedilol groups were 522.0+/-19.5 (n=6), 664.7+/-46.2 (n=7), 567.8+/-14.3 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of -100 mV, inward I(Ki) density (pA/pF) in control, banded, and Carvedilol groups were -11.8+/-0.50 (n=8), -8.07+/-0.28 (n=8), -10.69+/-0.35 (n=8) respectively (banded vs control and Carvedilol, P<0.01). At test potential of +50 mV, I(K) tail current density (pA/pF) in control, banded, and Carvedilol groups were 0.59+/-0.04 (n=8), 0.40+/-0.02 (n=9), 0.51+/-0.02 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of +60 mV, outward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were 1.06+/-0.11 (n=8), 1.54+/-0.10 (n=9), 1.24+/-0.07 (n=8), respectively (banded vs control and Carvedilol, P<0.01). At test potential of -120 mV, inward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were -0.54+/-0.06 (n =8), -0.75+/-0.04 (n=9), -0.60+/-0.03 (n=8), respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). It is shown that long-term treatment with Carvedilol not only prevents development of cardiac hypertrophy, but also improves the electrophysiological alterations in rabbit hearts with chronic pressure-overload. This finding may add new electrophysiological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.
进行实验以研究肾上腺素能受体拮抗剂长期治疗对慢性压力超负荷所致左心室电重构的影响。对新西兰兔进行肾下腹主动脉部分结扎。术后10周，进行超声心动图检查，然后采用全细胞膜片钳技术记录腹主动脉结扎组（结扎组）、腹主动脉结扎加卡维地洛干预组（卡维地洛组）和正常对照组兔左心室中层心肌细胞的动作电位（AP）、内向整流钾电流（I(Ki)）、延迟整流钾电流（I(K)）和钠钙交换电流（I(Na(+)/Ca(2+))）。结果显示，对照组、结扎组和卡维地洛组的左心室质量指数分别为1.78±0.06（n = 7）、2.33±0.11（n = 7）和1.87±0.08（n = 7）（结扎组与对照组和卡维地洛组相比，P<0.01）。在基础周期长度为2 s时，对照组、结扎组和卡维地洛组的动作电位时程（在复极化90%时测量，APD(90)，ms）分别为522.0±19.5（n = 6）、664.7±46.2（n = 7）、567.8±14.3（n = 8）（结扎组与对照组相比，P<0.01；卡维地洛组与结扎组相比，P<0.05）。在测试电位为 -100 mV时，对照组、结扎组和卡维地洛组的内向I(Ki)密度（pA/pF）分别为 -11.8±0.50（n = 8）、 -8.07±0.28（n = 8）、 -10.69±0.35（n = 8）（结扎组与对照组和卡维地洛组相比，P<0.01）。在测试电位为 +50 mV时，对照组、结扎组和卡维地洛组的I(K)尾电流密度（pA/pF）分别为0.59±0.04（n = 8）、0.40±0.02（n = 9）、0.51±0.02（n = 8）（结扎组与对照组相比，P<0.01；卡维地洛组与结扎组相比，P<0.05）。在测试电位为 +60 mV时，对照组、结扎组和卡维地洛组的外向I(Na(+)/Ca(2+))密度（pA/pF）分别为1.06±0.11（n = 8）、1.54±0.10（n = 9）、1.24±0.07（n = 8）（结扎组与对照组和卡维地洛组相比，P<0.01）。在测试电位为 -120 mV时，对照组、结扎组和卡维地洛组的内向I(Na(+)/Ca(2+))密度（pA/pF）分别为 -0.54±0.06（n = 8）、 -0.75±0.04（n = 9）、 -0.60±0.03（n = 8）（结扎组与对照组相比，P<0.01；卡维地洛组与结扎组相比，P<0.05）。结果表明，卡维地洛长期治疗不仅可预防心脏肥大的发展，还可改善慢性压力超负荷兔心脏的电生理改变。这一发现可能为肾上腺素能受体拮抗剂治疗心力衰竭和高血压增添新的电生理证据。
