Differential Effects of Heart Rate Reduction and Beta-blockade on Left Ventricular Relaxation During Exercise

Left ventricular (LV) relaxation is crucial for LV function, especially during exercise. We compared the effects of increasing doses of ivabradine, a selective inward hyperpolarization-activated current inhibitor, and atenolol on the rate and extent of LV relaxation (best fit method: time constant tau(BF), pressure asymptote P(BF)) at rest and during exercise. Eight dogs were chronically instrumented to measure LV pressure and LV wall stresses. During exercise under saline, heart rate increased from 108 +/- 5 to 220 +/- 6 beats/min and tau(BF) was significantly reduced from 22 +/- 1 to 14 +/- 2 ms. At rest, atenolol but not ivabradine increased tau(BF). For similar heart rate reductions during exercise, atenolol impeded the shortening of tau(BF) (23 +/- 2 ms) whereas ivabradine had no effect (15 +/- 2 ms). The extent of the relaxation process (P(BF)) at peak exercise was increased by ivabradine, and to a greater extent by atenolol, compared with saline. Thus, for a similar reduction in heart rate at rest and during exercise, ivabradine, in contrast with atenolol, does not exert any negative lusitropic effect.