Heart rate reduction by inhibition of If or by beta-blockade has different effects on postsystolic wall thickening.

Abstract:

BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: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). KEY RESULTS: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. CONCLUSION AND IMPLICATIONS: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.

journal_name

Br J Pharmacol

authors

Lucats L,Ghaleh B,Colin P,Monnet X,Bizé A,Berdeaux A

doi

10.1038/sj.bjp.0706996

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

335-41

issue

3

eissn

0007-1188

issn

1476-5381

pii

0706996

journal_volume

150

pub_type

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