肾上腺素能受体阻断剂预防慢性压力超负荷左心室的电重构(英文)

Adrenergic receptor antagonist prevents the left ventricle with chronic pressure-overload from electrical remodeling

研究长期使用肾上腺素能受体阻断剂治疗对慢性压力超负荷左心室电重构的影响。新西兰兔通过肾上腹主动脉次全结扎诱发慢性压力超负荷,10周后行心脏超声检查,并采用全细胞膜片钳技术分别记录腹主动脉结扎组(简称结扎组)、腹主动脉结扎+Carvedilol 干预组(简称Carvedilol组)及正常对照组(简称对照组)动物左室肌中层细胞的动作电位(action potential,AP)、内向整流钾电流(inward rectifier potassium current,IKi)、延迟整流钾电流(delayed rectifier potassium current,IK)及Na+/Ca2+交换体电流。结果表明,结扎组的左室质量指数较对照组明显升高,Carvedilol组较结扎组明显降低(P<0.01)。在2 s的基础周长下,动作电位持续时间(以90％的复极时间表示,简称APD90)在对照组、结扎组及Carvedilol组分别为522.0±19.5 ms(n=6)、664.7± 46.2 ms(n=7)、567.8±14.3 ms(n=8),结扎组同对照组相比,P<0.01,Carvedilol组同结扎组相比,P<0.05。在测试电位为-100mV时,IKi电流密度(pA/pF)在对照组、结扎组及Carvedilol组分别为-11.8±0.50(n=8),-8.07±0.28 (n=8),-10.69±0.35(n=8),结扎组与对照组及Carvedilol组相比,P<0.01。在测试电位为+50 mV时,IK尾电流密度(pA/pF)在对照组、结扎组及Carvedilol组分别为0.59±0.

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 (IKi), delayed rectifier potassium current (IK) and Na+/Ca2+ exchanger current (INa+/Ca2+) 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, APD90, 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 IKi 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, IK 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 INa+/Ca2+ 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 INa+/Ca2+ 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 electrophysi-ological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.