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


METHODS
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).


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.


CONCLUSIONS
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.
Lucats
L
L
INSERM, U 660, Créteil, France.
Ghaleh
B
B
Colin
P
P
Monnet
X
X
Bizé
A
A
Berdeaux
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000187:drug effects*; D000077550:Ivabradine; D009206:Myocardium; D010805:Physical Conditioning, Animal
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine; D001262:Atenolol