Enhanced in vivo and in vitro contractile responses to β2-adrenergic receptor stimulation in dogs susceptible to lethal arrhythmias
Enhanced in vivo and in vitro contractile responses to β2-adrenergic receptor stimulation in dogs susceptible to lethal arrhythmias
复制标题
DOI：
10.1152/jappl.2001.91.4.1627
复制
发表时间：
2001-10-01
影响因子：
3.3
通讯作者：
Billman, GE
中科院分区：
文献类型：
--
作者：
Houle, MS;Altschuld, RA;Billman, GE
在分离的心肌细胞（视频边缘检测）和完整的动物（超声心动图）中，对运动最后一分钟冠脉闭塞2分钟引起的心室颤动敏感(S)或抵抗(R)的狗，评估了对β -肾上腺素能受体（β -AR）刺激的反应。在完整动物心肌梗死前（n = 27, S = 12, R = 15）和心肌梗死后分别测定心肌纤维周向缩短速度（Vcf）。在梗塞前，增加异丙肾上腺素的剂量在各组狗中引起相似的收缩和心率反应。β (1)-AR（比索洛尔）或β (2)-AR （ci -118551）拮抗剂均可降低异丙肾上腺素反应，阻断β (1)-AR后降低幅度更大。相反，在梗死后，异丙肾上腺素在易感动物中诱导了明显更大的Vcf和心率反应，而β (2)-AR阻断可以消除这种反应。与耐药犬相比，易感犬的细胞对异丙肾上腺素（100 nM）的单细胞等张缩短反应也更大，并且在易感犬的肌细胞中，β (2)- ar阻断更大程度上降低了这种反应（S, - 48%, n = 6； R, - 15%, n = 9）。综合考虑，这些数据表明心肌梗死在易感动物而非耐药动物中引起了增强的β (2)-AR反应。
The response to beta -adrenergic receptor (beta -AR) stimulation was evaluated in both isolated cardiomyocytes (video edge detection) and the intact animal (echocardiography) in dogs either susceptible (S) or resistant (R) to ventricular fibrillation induced by a 2-min coronary occlusion during the last minute of exercise. In the intact animal, velocity of circumferential fiber shortening (Vcf) was evaluated both before (n = 27, S = 12 and R = 15) and after myocardial infarction. Before infarction, increasing doses of isoproterenol provoked similar contractile and heart rate responses in each group of dogs. Either beta (1)-AR (bisoprolol) or beta (2)-AR (ICI-118551) antagonists reduced the isoproterenol response, with a larger reduction noted after the beta (1)-AR blockade. In contrast, after infarction, isoproterenol induced a significantly larger Vcf and heart rate response in the susceptible animals that was eliminated by beta (2)-AR blockade. The single-cell isotonic shortening response to isoproterenol (100 nM) was also larger in cells obtained from susceptible compared with resistant dogs and was reduced to a greater extent by beta (2)-AR blockade in the susceptible dog myocytes (S, - 48%, n = 6; R, - 15%, n = 9). When considered together, these data suggest that myocardial infarction provoked an enhanced beta (2)-AR response in susceptible, but not resistant, animals.