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

• Published in: Journal of the American College of Cardiology Vol. 33; no. 6; pp. 1602 - 1609
• Main Authors: Chen, Chen-Huan, Nakayama, Masaru, Talbot, Maurice, Nevo, Erez, Fetics, Barry, Gerstenblith, Gary, Becker, Lewis C, Kass, David A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-1999; Elsevier Science
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cardiovascular system; Cross-Over Studies; Double-Blind Method; Exercise Test - drug effects; Female; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Male; Medical sciences; Middle Aged; Myocardial Contraction - drug effects; Pharmacology. Drug treatments; Stroke Volume - drug effects; Treatment Outcome; Vascular Resistance - drug effects; Vasodilator agents. Cerebral vasodilators; Ventricular Function, Left - drug effects; Verapamil - pharmacology; EF; SV; V̇O2; AI; ESV; PWRmax; PWV; Ees; AT; EDV; Psys; Ea; Pes; PFREDV; Human; Physical exercise; Pharmacologic test; Vasodilator agent; Intravenous administration; Blood vessel; Aralkylamine; Heart ventricle; Verapamil; Stiffness; Aerobe; Elderly
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(99)00052-2

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.