Ramp work tests with three different beta-blockers in normal human subjects

Summary

The effects ofβ-blockade on the responses of oxygen uptake ($\dot V_{{\text{O}}_{\text{2}} }$), heart rate (HR) and blood lactate (La⁻) were examined during ramp cycle ergometer tests (50 W·min⁻¹ ramp slope) in 8 healthy male volunteers. Each subject took placebo, or one of four different doses of three differentβ-blockers (propranolol, metoprolol or oxprenolol) 2 h prior to each test for a total of 15 exercise tests. ($\dot V_{{\text{O}}_{\text{2}} }$) was measured breath-by-breath, HR was sampled once per breath, and La⁻ was obtained every minute. Linear regression analysis was applied to$\dot V_{{\text{O}}_{\text{2}} }$ and HR data to obtain the kinetic parameter total lag time (TLT) and a slope value. La⁻ was analyzed by a continuous exponential model with the lactate slope index (LSI) being derived from the individual response curves. Submaximal exercise HR was significantly depressed at the baseline as well as during the ramp tests byβ-blockade. TLT for HR was significantly affected byβ-blockade, with a dose dependent shift from a placebo value of 16 to 26 s with placebo to a value of -40 to -60 s at the highest dose. Slope of HR was significantly depressed relative to placebo.$\dot V_{{\text{O}}_{\text{2}} }$ kinetics assessed by TLT were not significantly affected byβ-blockade. This slope of the$\dot V_{{\text{O}}_{\text{2}} }$ vs work rate relationship was significantly less than placebo only at the highest dose ofβ-blocker. The LSI was not significantly affected byβ-blockade. In contrast with the clear impairment of HR response to exercise duringβ-blockade, both the$\dot V_{{\text{O}}_{\text{2}} }$ and La⁻ responses appear to be relatively unaffected byβ-blockade during ramp exercise tests. However, the significant change in slope of the$\dot V_{{\text{O}}_{\text{2}} }$ vs work rate relationship at the highest dose level indicates that the oxygen transport system is in fact impaired byβ-blockade. It is concluded that the ramp exercise test is not a sensitive means of detecting changes in oxygen transport kinetics during exercise withβ-blockade. Further, there were no differences between the threeβ-blocking drugs.