Failure of Aminophylline and Salbutamol to Improve Respiratory Muscle Function and Exercise Tolerance in Healthy Humans

Abstract

We investigated the effects of intravenously administered aminophylline (A; 6 mg/kg over 20 min, followed by 0.9 mg/kg/h), salbutamol (S; 4 µg/kg over 20 min, followed by 3 µg/kg/h) and placebo (P; saline solution) on the strength of the respiratory muscles, the ventilatory endurance and the exercise tolerance in 7 healthy humans. Neither A nor S caused bronchodilatation, as shown by the lack of change in FEV₁. The strength of respiratory muscles, as measured by maximal inspiratory pressure (MIP), and the ventilatory endurance, as measured by sustainable inspiratory pressure (SIP), were not statistically different after A (MIP: 136.5 ± SE 11.6 cm H₂O; SIP: 104.2 ± 8.4 cm H₂O or after S (MIP: 135.7 ± 11.5; SIP: 107.1 ± 10.4) compared to after P (MIP: 127.1 ± 10.1; SIP: 105.0 ± 5.9). Significant changes in 12-min walking distance, perceived exertion rate, anaerobic threshold, maximal work output, maximal O₂ uptake were observed neither after A nor after S. The exchange ratio and heart rate were higher after A and S than after P at some steps of a progressive, symptom-limited, treadmill-based exercise test. This might be the result of metabolic or cardiovascular adaptations elicited by these drugs. We conclude that A or S at therapeutic concentrations have no clinically relevant beneficial effects on ventilatory muscle function and exercise tolerance in healthy subjects.

Effects of β2-adrenergic stimulation on exercise capacity in normal subjects

“…This result is in keeping with previous reports (McKenzie et al 1983;Violante et al 1989;Malerba et al 1996;Carlsen et al 1997), and conWrmed in the present study with the highest possible tolerated dose given intravenously. It thus appears that 2 agonist-induced increases in stroke volume, indirectly suggested by increased pulse pressures and O 2 pulse in the present experiments, related to positive inotropic eVects and increased venous return (Hopkins et al 1996), cannot contribute to an improved aerobic exercise capacity through and increased O 2 delivery to the exercising muscles.…”

Effects of theophylline and theobromine on exercise performance and implications for competition sport: A systematic review

“…Muscle strength was evaluated by somewhat differing methods. In an investigation of muscle metabolism, there was an increase in forearm muscular endurance that was considered due to a delayed onset of intracellular metabolic acidosis 27 . But this is an interesting finding and may account for the delayed onset of ischaemic arm pain found by Jonzon, given a meta‐analysis of pain perception showed that a wide spectrum of sportspeople have higher pain thresholds than the normally active controls 33 .…”

“…aminophylline and salbutamol at therapeutic concentrations have no clinically relevant beneficial effects on ventilatory muscle function and exercise tolerance in healthy subjects 27 …”

“…There were differences in anaerobic threshold, PER, maximal workload or 12‐min walk between the three arms of the study. The authors concluded:

aminophylline and salbutamol at therapeutic concentrations have no clinically relevant beneficial effects on ventilatory muscle function and exercise tolerance in healthy subjects 27

…”

β2‐adrenergic agonists do not improve physical performance in healthy individuals

“…These results, despite being somewhat inconsistent due to the lack of studies, agree with other studies already performed. 4,5 Regarding inhaled β2-agonists' effect on endurance TTE, no significant effect was shown. However, when considering the oral route, the effect was statistically significant for salbutamol, which explains the prohibition of this route of administration for athletes granted a TUE.…”