The effects of β1-adrenergic blockade on cardiovascular oxygen flow in normoxic and hypoxic humans at exercise

Abstract

At exercise steady state, the lower the arterial oxygen saturation (SaO₂), the lower the O₂ return $(\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}).$ A linear relationship between these variables was demonstrated. Our conjecture is that this relationship describes a condition of predominant sympathetic activation, from which it is hypothesized that selective β1-adrenergic blockade (BB) would reduce O₂ delivery $(\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2} )$ and $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2} .$ To test this hypothesis, we studied the effects of BB on $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2}$ and $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ in exercising humans in normoxia and hypoxia. O₂ consumption $(\ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} ),$ cardiac output $(\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}, CO_{2}\; \hbox{rebreathing}),$ heart rate, SaO₂ and haemoglobin concentration were measured on six subjects (age 25.5±2.4 years, mass 78.1±9.0 kg) in normoxia and hypoxia (inspired O₂ fraction of 0.11) at rest and steady-state exercises of 50, 100, and 150 W without (C) and with BB with metoprolol. Arterial O₂ concentration (CaO₂), $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2},$ and $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ were then computed. Heart rate, higher in hypoxia than in normoxia, decreased with BB. At each $\ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} ,$ $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}$ was higher in hypoxia than in normoxia. With BB, it decreased during intense exercise in normoxia, at rest, and during light exercise in hypoxia. SaO₂ and CaO₂ were unaffected by BB. The $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2}$ changes under BB were parallel to those in $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}.$ $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ was unaffected by exercise in normoxia. In hypoxia the slope of the relationship between $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}{\text{aO}}_{2}$ and $\ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2}$ was lower than 1, indicating a reduction of $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ with increasing workload. $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ was a linear function of SaO₂ both in C and in BB. The line for BB was flatter than and below that for C. The resting $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ in normoxia, lower than the corresponding exercise values, lied on the BB line. These results agree with the tested hypothesis. The two observed relationships between $\ifmmode\expandafter\dot\else\expandafter\.\fi{Q}\bar{{\text{v}}} {\text{O}}_{2}$ and SaO₂ apply to conditions of predominant sympathetic or vagal activation, respectively. Moving from one line to the other implies resetting of the cardiovascular regulation.