Conversion of postsystolic Into ejectional wall thickening by selective heart rate reduction during stunning

Abstract

Postsystolic wall thickening (PSWT) occurs after aortic valve closure. This waste of thickening does not participate to ejection. PSWT increases with myocardial ischemia and stunning but the effects of antianginal drugs on PSWT during myocardial dysfunction remains unknown. The effects of two heart rate reducing agents, i.e., the beta-blocker atenolol and the selective If current inhibitor ivabradine, were compared on PSWT. For this purpose, coronary stenosis was calibrated in 6 conscious instrumented dogs to suppress increase in coronary blood flow during a 10-min treadmill exercise to induce myocardial stunning. After exercise completion, stenosis was relieved and saline, atenolol or ivabradine (both at 1 mg/kg iv) were administered. During recovery and although heart rate was similarly reduced (−20% vs. saline), systolic wall thickening was improved by ivabradine while it was further depressed with atenolol as compared to saline (e.g., 2.0±0.4 and 1.2±0.2 vs. 1.7±0.3 mm at 1 h recovery, respectively). Importantly, PSWT to total wall thickening ratio was significantly decreased by ivabradine vs. saline whereas total wall thickening was similar. Thus ivabradine devoted a greater part of thickening to systole. In contrast, atenolol failed to reduce PSWT vs. saline. Atrial pacing abolished the effects of ivabradine but not those of atenolol. In conclusion, selective heart rate reduction with ivabradine converts PSWT into ejectional thickening but not with atenolol secondary to its negative inotropism.