Ablad Bengt, Bjurö Thorvald, Björkman Jan-Arne, Edström Therese
AstraZeneca R&D, Mölndal, Sweden.
Scand Cardiovasc J. 2007 Aug;41(4):221-9. doi: 10.1080/14017430701383748.
To study whether and how a lipophilic and a hydrophilic beta-adrenoceptor antagonist affects ventricular fibrillation (VF) after coronary artery occlusion in a rabbit model with high sympathetic and low cardiac vagal activation.
Rabbits were treated for 3 weeks (series 1) or 2 hours (series 2) with metoprolol, atenolol or control vehicle. Finally the animals in series 1 were exposed to coronary artery occlusion. Heart rate response to cholinergic blockade was studied in series 2.
The incidence of postocclusion VF in metoprolol animals was lower (p<0.05) than that in atenolol or control animals. The two beta-blockers caused similar reductions of heart rate, arterial pressure and myocardial ischemia. However, metoprolol animals had more respiratory sinus arrhythmia higher baroreflex sensitivity and more pronounced tachycardic response to cholinergic blockade than atenolol animals.
Metoprolol reduced the incidence of VF by a better maintained discharge than atenolol in efferent cardiac vagal nerves, possibly due to inhibition of central nervous beta(1) adrenoceptors modulating vagal nervous outflow.
研究在高交感神经活性和低心脏迷走神经活性的兔模型中,一种亲脂性和一种亲水性β-肾上腺素能拮抗剂是否以及如何影响冠状动脉闭塞后的心室颤动(VF)。
用美托洛尔、阿替洛尔或对照载体对兔子进行3周(系列1)或2小时(系列2)的治疗。最后,系列1中的动物接受冠状动脉闭塞。在系列2中研究了对胆碱能阻断的心率反应。
美托洛尔组动物闭塞后VF的发生率低于阿替洛尔组或对照组动物(p<0.05)。两种β受体阻滞剂对心率、动脉压和心肌缺血的降低作用相似。然而,与阿替洛尔组动物相比,美托洛尔组动物有更多的呼吸性窦性心律不齐、更高的压力反射敏感性以及对胆碱能阻断更明显的心动过速反应。
美托洛尔通过比阿替洛尔更好地维持传出心脏迷走神经的放电来降低VF的发生率,这可能是由于抑制了调节迷走神经流出的中枢神经β1肾上腺素能受体。