Factors contributing to increased muscle fatigue with β-blockers

Abstract

beta-Adrenoceptor blockers are widely used clinically and can be classified as nonselective (beta 1 and beta 2) or selective (beta 1). Impairment of exercise performance is a well-known side effect of this group of drugs. This paper reviews mechanisms that could potentially be responsible for this impairment. In addition to cardiovascular and metabolic effects, beta-blockade inhibits Na(+)-K+ ATPase pumps controlling ion movement between muscle and plasma and thus may contribute to muscle fatigue through this mechanism. To investigate the relationship between the change in plasma [K+] and exercise performance, we studied healthy male subjects taking propranolol. Eight subjects performed maximal incremental cycle ergometer exercise tests during control (no drug), low dose (LD) (40 mg daily), and high dose (HD) (265 +/- 4.3 (SE) mg daily) of propranolol. The control plasma [K+] (5.8 +/- 0.12 mequiv./L) during exercise was significantly lower than either the LD (6.4 +/- 0.05 mequiv./L) or HD (6.1 +/- 0.16 mequiv./L) values. There was no significant difference between plasma [K+] for the LD and HD of propranolol. However, maximum oxygen uptake was reduced only while taking the HD of propranolol. Six of the subjects also performed three 30-s bouts of high intensity exercise on an isokinetic cycle ergometer while taking the LD and HD of propranolol. There was no significant difference between doses for the increase in plasma [K+] (LD, 7.8 +/- 0.35 mequiv./L vs. HD, 7.6 +/- 0.36 mequiv./L) during exercise. However, exercise performance was significantly reduced during HD compared with LD. These results suggest that the increases in plasma [K+] with propranolol did not play a direct significant role in the reduced performance observed during the HD.

Effects of Propranolol and Exercise Training in Children with Severe Burns

“…Although beta blockade is linked to reduced exercise performance in other patient populations (9, 10, 40, 46), our data validates the safety profile of this therapeutic agent in children. In both the EX and PROPEX groups, significant improvements in muscle strength, LBM, and cardiopulmonary capacity were not accompanied by any evidence of adverse events during the study period (31).…”

“…These effects are associated with reduced oxygen transport (9), increased muscle fatigue (10), and reduced availability of energy substrate (12, 13, 40). In the presence of propranolol, the workload-VO 2 relationship is maintained during submaximal exercise, suggesting that oxygen delivery is increased under these conditions as an adaptive mechanism.…”

The Role of Exercise in the Rehabilitation of Patients with Severe Burns

“…While a mechanistic explanation as to why propranolol and exercise have an additive effect on VO 2 peak in burned children is currently lacking, the ability of propranolol to attenuate peripheral protein catabolism and blood flow (12) may contribute to improved muscle mass and quality as well as O 2 extraction from arterial blood. However, it is important to note that, while β blockade is associated with detriments in muscle function in healthy adults (22), this is not the case in severely burn children.…”

Effect of progressive incremental exercise and β-adrenergic blockade on erythrocyte ion concentrations

“…β-Blockade (βb) has been found to impair exercise capacity in healthy individuals, but the mechanisms responsible for this effect have not been fully elucidated (McKelvie et al 1991a). An increase in plasma [K + ] has been suggested as a possible mechanism for the increase in fatigability for individuals on βb (McKelvie et al 1991a).…”

“…An increase in plasma [K + ] has been suggested as a possible mechanism for the increase in fatigability for individuals on βb (McKelvie et al 1991a). Although Katz et al (1985) found no difference between placebo and βb on K + release across exercising muscle, plasma [K + ] was elevated.…”