$\dot V{O_2}$ on-Transient Kinetics with a Centrally Acting Calcium Channel Blocker

Abstract

We (1) have recently shown that maximal aerobic capacity $(\dot V{O_{2\max }})$ is increased significantly in normal elderly subjects coincident with improved left ventricular diastolic function following ingestion of the centrally acting Ca²⁺ channel blocker, verapamil. In addition, we have shown that exercise training has resulted in increased $\dot V{O_{2\max }}$ and faster gas exchange kinetics among the elderly (2). Hughson and Smyth (3) reported a slower increase of $\dot V{O_2}$ to steady state with submaximal exercise and Tesch and Kaiser (4) reported a lower $\dot V{O_{2\max }}$ under the influence of β-adrenergic blockade in normal young subjects. The slowed responses in elderly subjects (2) and younger subjects (3) during β-adrenergic blockade may reflect impaired central or peripheral components of the $\dot V{O_2}$ response (5,6). Whipp et al. (7) have described the kinetics of the gas transport system by a first order model and termed the initial 20s of the $\dot V{O_2}$ response “cardiodynamic”. This period reflects the central or cardiac component of the $\dot V{O_2}$ on-transient (Phase 1). The effects of a centrally acting Ca²⁺ channel blocker which increased $\dot V{O_{2\max }}$ and improved left ventricular function in the elderly (1), may also be reflected in improved kinetics in the non-steady state response to an exercise perturbation. This may result from improvement in the central component of the $\dot V{O_2}$ on-transient response. In order to examine this, we have analyzed the gas exchange responses in elderly men to a step increase in power output to a sub-anaerobic threshold level (40 W) before and 4 hours after ingestion of 240mg of verapamil SR.