Lucats L, Ghaleh B, Colin P, Monnet X, Bizé A, Berdeaux A
INSERM, U 660, Créteil, France.
Br J Pharmacol. 2007 Feb;150(3):335-41. doi: 10.1038/sj.bjp.0706996. Epub 2006 Dec 18.
Postsystolic wall thickening (PSWT) is part of thickening that occurs after end-systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the beta-blocker atenolol and the selective inhibitor of If current, ivabradine.
Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1 mg.kg-1) or ivabradine (1 mg.kg-1).
Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35+/-0.07 vs 0.21+/-0.03 mm, respectively) and during exercise (0.30+/-0.04 vs 0.15+/-0.04 mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80+/-23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant tau and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing.
For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection.
收缩期后心肌增厚(PSWT)是在收缩末期之后发生的心肌增厚的一部分,由于其对射血无贡献,因而代表了无效做功。抗心绞痛药物对PSWT的影响尚待确定。我们比较了两种降低心率的药物——β受体阻滞剂阿替洛尔和If电流选择性抑制剂伊伐布雷定——对PSWT的影响。
对6只犬进行准备,以便在清醒状态下、静息时以及运动期间,在给予生理盐水、阿替洛尔(1mg·kg⁻¹)或伊伐布雷定(1mg·kg⁻¹)后,通过超声微测法测量心肌增厚情况。
与生理盐水相比,阿替洛尔和伊伐布雷定在静息时(约10% - 20%)和运动期间(约30%)同样降低了心率。阿替洛尔降低了dP/dtmax,而伊伐布雷定未降低。同时,与生理盐水相比,静息时(分别为0.35±0.07mm和0.21±0.03mm)以及运动期间(分别为0.30±0.04mm和0.15±0.04mm),阿替洛尔使PSWT增加。相比之下,伊伐布雷定未改变PSWT。重要的是,阿替洛尔使收缩期后与收缩期心肌增厚的比值增加了80±23%,而伊伐布雷定未增加。阿替洛尔引起的舒张期增厚增强伴随着左心室等容舒张受阻,这通过等容舒张时间常数tau与收缩期后与收缩期心肌增厚比值之间的显著相关性得以体现。当通过心房起搏控制心率时,阿替洛尔的这些作用均未被消除。
在静息时和运动期间使心率降低程度相似的情况下,伊伐布雷定而非阿替洛尔未改变PSWT,并保留了对射血有贡献的增厚部分。