心力衰竭大鼠β_3-肾上腺素能受体兴奋对室颤阈值和心室有效不应期的影响

Effect of β_3-adrenoceptor activation on ventricle fibrillation threshold and effective refractory period in rats with heart failure

目的:观察实验性心力衰竭大鼠左心室β3-肾上腺素能受体(AR)表达水平的变化及β3-AR激动时对心脏室颤阈值(VFT)和心室有效不应期(ERP)的影响。方法:雄性成年Wistar大鼠16只,随机分为心力衰竭组(n=8)及对照组(n=8)。结扎大鼠冠状动脉前降支致心肌梗死建立心力衰竭模型;使用RT-PCR法检测左心室β3-AR mRNA的表达;观察使用β3-AR激动剂BRL37344对VFT、ERP和LVESP、+dp/dtmax、-dp/dtmax的影响。结果:①与对照组相比,心力衰竭大鼠左心室β3-AR mRNA表达量(β3/β-actin的比值)增加(0.011vs0.028,P<0.05),所占比例(β3/β1+β2+β3)增加(1.2%vs5.4%,P<0.05);②心力衰竭大鼠VERP较正常对照组VERP明显延长(70.5ms±5.5msvs59.5ms±6.4ms,P<0.05);静注BRL37344后,心力衰竭大鼠VERP稍延长,但对比用药前VERP无显著差异(73.0ms±4.8msvs70.5ms±5.5ms,P>0.05);③心力衰竭大鼠VFT较正常对照组VFT显著降低(10.9mV±0.8mVvs30.5mV±1.3mV,P<0.05);静注BRL37344后,心力衰竭大鼠VFT相比用药前亦显著降低(7.1mV±0.6mVvs10.9mV±0.8mV,P<0.05);BRL37344降低VFT的作用与BRL37344对LVESP、+dp/dtmax、-dp/dtmax及β3-AR mRNA表达量的改变密切相关,相关系数分别为0.788、0.708、0.759、0.787(P<0.05)。结论:心力衰竭大鼠左心室β3-AR mRNA表达明显增高,β3-AR激动时不影响衰竭大鼠心室ERP,但明显降低衰竭大鼠心脏VFT,其降低VFT作用与β3-AR的负性肌力作用及β3-AR mRNA表达量的改变密切相关。

AIM ： To observe the effect of β3 - adrenoceptor （AR） on ventricle fibrillation threshold （VFT） and effective refractory period （ERP） in rats with heart failure. METHODS： Rats were randomized into control group and heart failure group. The expression of β3 - AR mRNA was detected with RT - PCR. The VFT, ERP, left ventricle end - systolic pressure（LVESP） ,left ventricle end -diastolic pressure（ LVEDP）, ± dp/dtmax and - dp/dtmax were measured at the same time with administration of BRL37344 （ β3 - AR agonist）. RESULTS： ① Both the expression of β3 - AR mRNA and the proportion （ β3/β1 ±β2 ± β3 ） were increased in failure rats comparied with those in control rats （0. 028 vs 0. 011 and 5.4% vs 1.2%, P 〈0.05）. ② ERP was longer in rats with heart failure than that in control group （70. 5 ms ± 5.5 ms vs 59. 5 ms ± 6. 4 ms, P 〈 0.05）. No difference in ERP in rats with heart failure was observed before and after administration of BRL37344 （73.0 ms ± 4. 8 ms vs 70. 5 ms ± 5.5 ms, P 〉 0. 05 ）. ③VFT was lower in rats with heart failure than that in control group （ 10. 9 mV ± 0. 8 mV vs 30. 5 mV ± 1.3 mV, P 〈 0. 05 ） and decreased obviously in rats with heart failure after administration of BRL37344 （7.1 mV ± 0. 6 mV vs 10. 9 mV ± 0. 8 mV, P 〈 0.05 ）. The decrease in VFT correlated with the effect of LVESP, ± dp/dtmax, - dp/dtmax with BRL37344 and the expression of β3 - AR mRNA （ correlation coefficient： 0. 788, 0. 708, 0. 759, 0. 787 ; P 〈 0.05 ）. CONCLUSION： The expression of β3 - AR mRNA in left ventricle is obviously increased in rats with heart failure. The activation of β3 - AR has no effect on ERP but can decrease VFF which correlates with the effect of β3 - AR on LVESP, ± dp/dtmax, - dp/dtmax and the expression of β3 - AR mRNA.