Role of the Frank-Starling mechanism in maintaining cardiac output during increasing levels of treadmill exercise in beta-blocked normal men

Abstract

To determine the effects of β blockade on hemodynamics during increasing levels of treadmill exercise, 10 healthy volunteers were studied after 1 week of placebo, and then after 1 week of treatment with oral propranolol, 80 mg twice daily, or dilevalol, 400 mg once daily. The study was randomized and double-blind, with a crossover sequence. Hemodynamics were measured by CO 2 rebreathing at rest and at 25, 50, 75 and 100% of V̇O 2 max. After placebo, cardiac output increased from 5.8 ± 2.1 (rest), to 19.4 ± 6.4 liters/min (100% V̇O 2 max), mainly due to an increase in heart rate from 84 ± 6 to 169 ± 15 beats/min. Stroke volume increased from 70 ± 27 (rest), to 137 ± 65 ml (25% V̇O 2 max), and then leveled off to 116 ± 41 at 100% V̇O 2 max. After both β blockers, exercise cardiac output was maintained at 100% V̇O 2 max: 20.1 ± 9.3 liters/min with propranolol and 19.1 ± 8.6 with dilevalol. However, a significant reduction versus placebo values was observed for cardiac output at 25% V̇O 2 max, from 13.7 ± 5.9 during placebo, to 9.4 ± 2.5 during propranolol, and to 9.6 ± 2.3 during dilevalol (both p <0.01 vs placebo). Maintenance of cardiac output with both β blockers at higher levels of exercise came from an increased stroke volume (p <0.05 vs placebo), while heart rate (in beats/min) was greatly reduced (propranolol 61.6 ± 9.4 rest, 90.1 ± 10.7 at 100% V̇O 2 max; dilevalol 70.8 ± 6.4 rest, 99.2 ± 11.8 at 100% V̇O 2 max, p <0.01 vs placebo for each). All subjects were able to exercise up to maximal control level during β-blocker treatment. The decrease in total peripheral resistances was already evident at 25% V̇O 2 max and was not counteracted by β blockade. Thus, in normal volunteers, β blockers do not reduce exercise cardiac output, even at doses that greatly reduce heart rate. At low levels of exercise, a transient blunting of cardiac output increase probably reflects a delay in sympathetic activation. At higher exercise levels, an increase in stroke volume, that is an effective Frank-Starling mechanism, allows maintained oxygen supply to the exercising muscles.