THE EFFECTS OF COMBINED TREATMENT WITH BETA(1)-SELECTIVE RECEPTOR ANTAGONISTS AND LIPID-LOWERING DRUGS ON FAT-METABOLISM AND MEASURES OF FATIGUE DURING MODERATE INTENSITY EXERCISE - A PLACEBO-CONTROLLED STUDY IN HEALTHY-SUBJECTS

Aims We examined the effects of different combinations of beta(1)-sele ctive adrenoceptor blockers and lipid-lowering drugs, on fat metabolis m and fatigue during moderate intensity exercise in 14 healthy young v olunteers. Methods The study was a randomized crossover design, each s ubject completing 5, 90 min walks at 50% of predetermined maximal oxyg en uptake (VO2 max), one following each 3 day treatment period with ei ther: atenolol 100 mg and bezafibrate 400 mg, atenolol 100 mg and fluv astatin 40 mg, metoprolol CR 100 mg and bezafibrate 400 mg, metoprolol CR 100 mg and fluvastatin 40 mg, or placebo. Results Plasma free fatt y acid (FFA) concentration during exercise was significantly reduced o n all treatments, in comparison with placebo, P=0.0001. Following 90 m in of exercise FFA levels were as follows: placebo 573 mu mol l(-1) (1 05-1041), metoprolol CR + fluvastatin 277 mu mol l(-1) (0-647), metopr olol CR + bezafibrate 182 mu mol l(-1) (0-396), atenolol + fluvastatin 211 mu mol l(-1) and atenolol + bezafibrate 123 mu mol l(-1) (0-352). Total fat oxidation during exercise was also reduced on all treatment s in comparison with placebo: 38.1% (2-74), compared with 29.1% (0-61) on metoprolol CR + fluvastatin, P=0.02, 26.2% (2-51) on metoprolol CR + bezafibrate, P=0.002, 25.5% (3-48) on atenolol + fluvastatin, P=0.0 09, and 22.8% (0-47) on atenolol + bezafibrate treatment, P=0.0002. Pl asma ammonia concentration was elevated on all treatments during exerc ise in comparison with placebo. After 90 min of exercise, plasma ammon ia levels were as follows: placebo 37 mu mol l(-1) (0-84), metoprolol CR + fluvastatin 56 mu mol l(-1) (2-110), metoprolol CR + bezafibrate 79 mu mol l(-1) (0-167), atenolol + fluvastatin 90 mu mol l(-1) (10-17 0), and atenolol + bezafibrate 100 mu mol l(-1) 26-174). In comparison with placebo, metoprolol CR + fluvastatin had the least adverse impac t on measures of perceived exertion and the 'feeling scale' during exe rcise. Metoprolol CR + bezafibrate, atenolol + fluvastatin, and atenol ol + bezafibrate treatments had greater adverse effects, particularly on perceived 'cardiorespiratory effort' and 'feeling scale' scores. Co nclusions In healthy volunteers, combinations of beta(1)-selective blo ckers and lipid-lowering drugs were associated with significant reduct ions in fat metabolism, increased plasma ammonia levels, and raised th e perception of effort during exercise, in comparison with placebo. Me toprolol CR + fluvastatin had the least effect, combinations metoprolo l CR + bezafibrate and atenolol + fluvastatin had intermediate effects , and atenolol + bezafibrate had the most adverse effect.