Contributions of Heart Rate and Contractility to Myocardial Oxygen Balance During Exercise

The respective contributions of heart rate (HR) reduction and left ventricular (LV) negative inotropy to the effects of antianginal drugs are debated. Accordingly, eight instrumented dogs were investigated during exercise at spontaneous and paced HR (250 beats/min) after administration of either saline, atenolol, or ivabradine (selective pacemaker current channel blocker). During exercise, atenolol and ivabradine (both 1 mg/kg iv) similarly reduced HR (−30% from 222 ± 5 beats/min), and LV mean ejection wall stress was not altered. LV dP/d t max was reduced by atenolol but not ivabradine. Diastolic time (DT) was increased by atenolol versus saline (195 ± 6 vs. 123 ± 4 ms, respectively) and to a greater extent by ivabradine (233 ± 11 ms). Myocardial oxygen consumption (MV˙o 2) was lower under ivabradine and atenolol versus saline (6.7 ± 0.6 and 4.7 ± 0.4 vs. 8.1 ± 0.6 ml/min, respectively, P < 0.05). Under pacing, DT and MV˙o 2 were similar between ivabradine and saline but significantly reduced with atenolol. Thus HR reduction and negative inotropy equally contribute to the reduction in MV˙o 2 during exercise in the normal heart. The negative inotropy limits the increase in DT afforded by HR reduction.