Verapamil acutely reduces ventricular-vascular stiffening and improves aerobic exercise performance in elderly individuals

OBJECTIVES: We tested the hypothesis that acute intravenous verapamil acutely enhances aerobic exercise performance in healthy older individuals in association with a combined reduction of ventricular systolic and arterial vascular stiffnesses. BACKGROUND: Age-related vascular stiffening coupled with systolic ventricular stiffening may limit cardiovascular reserve and, thus, exercise performance in aged individuals. METHODS: Nineteen healthy volunteers with mean age 70 ± 10 years underwent maximal-effort upright ergometry tests on two separate days after receiving either 0.15 mg/kg i.v. verapamil or 0.5 N saline in a double-blind, randomized, crossover study. RESULTS: Baseline vascular stiffness, indexed by arterial pulse-wave velocity (Doppler) and augmentation index (carotid tonometry) declined with verapamil (-5.9 ± 2.1% and -31.7 ± 12.8%, respectively, both p < 0.05). Preload- adjusted maximal ventricular power, a surrogate for ventricular end-systolic stiffness, also declined by -9.5 ± 3.6%. Peripheral resistance and peak filling rate were unchanged. With verapamil, exercise duration prior to the anaerobic threshold (AT) increased by nearly 50% (260 ± 129 to 387 ± 176 s) with a corresponding 13.4 ± 4.7% rise in oxygen consumption (V̇O₂) at that time (both p < 0.01). Total exercise duration prolonged by +6 ± 2.7% (p < 0.05) with no change in maximal V̇O₂. Baseline cardiodepression from verapamil reversed by peak exercise with net increases in stroke volume and Cardiac output (p < 0.05). CONCLUSIONS: Acute intravenous verapamil reduces ventriculovascular stiffening and improves aerobic exercise performance in healthy aged individuals. This highlights a role for heart-arterial coupling in modulating exertional capacity in the elderly, suggesting a potentially therapeutic target for aged individuals with exertional limitations.