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CLINICAL STUDIES

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

^a Division of Cardiology, Department of Medicine and Department of Biomedical Engineering, Johns Hopkins University Medical Institutions, Baltimore, Maryland, 21287, USA

Manuscript received June 26, 1998; revised manuscript received December 1, 1998, accepted January 20, 1999.

Reprint requests and correspondence: Dr. David A. Kass, Halsted 500, Division of Cardiology, The Johns Hopkins Hospital, 600 N Wolfe Street, Baltimore, Maryland 21287
dkass{at}eureka.wbme.jhu.edu

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 (O₂) at that time (both p < 0.01). Total exercise duration prolonged by +6 ± 2.7% (p < 0.05) with no change in maximal O₂. 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.

Abbreviations and Acronyms   AI = augmentation index   AT = anaerobic threshold   Ea = effective arterial elastance   EDV = end-diastolic volume   Ees = end-systolic elastance   EF = ejection fraction   ESV = end-systolic volume   Pes = end-systolic pressure   PFREDV = peak filling rate/EDV   Psys = arterial systolic pressure   PWRmax = maximal power   PWV = pulse wave velocity   SV = stroke volume   O2· = maximal oxygen consumption

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