Reversal of muscle fatigue in intact rabbits by intravenous potassium chloride

Abstract

Purpose: Skeletal muscle fatigue has been associated with potassium efflux from the myocytes, resulting in endogenous increases in blood potassium concentration ([K +]). Conversely, exogenous increases in extracellular [K +] potentiates contraction in isolated muscle preparations. The mechanisms responsible for these contradictory effects of [K +] on skeletal muscle function are unknown. Moreover, little is known about the effect of exogenous increases in [K +] on force generation by intact animals, given potassium's deleterious effect on cardiac function. Methods: We compared the response to exogenous increases in blood [K +] in rabbits given an infusion of potassium chloride (KCl) intravenously (IV) (0.2 mol/L; KCl group; n = 7) to a group given 0.9% sodium chloride (NaCl) (control; n = 7). The rabbits underwent low-frequency, isometric twitch stimulation of the left hindlimb (square wave pulses 100 microseconds, 40V, 0.25 Hz) throughout the experiment. Both groups received 0.9% NaCl (25 mL/h) during the first hour of twitch stimulation and experienced similar decreases in hindlimb forces to 70% of initial force. A continuous infusion of KCl or of saline (60 mL/h) was started, and hindlimb stimulation continued for 2 hours. Results: There were no changes in [K +] in the control group, and twitch forces progressively declined during the next 2 hours (369 ± 47 g to 279 ± 34 g, P < .01). Arterial [K +] increased in the KCI group from 2.6 ± 0.1 to 10.1 ± 0.5 mmol/L ( P <.01), and hindlimb twitch forces almost doubled (418 ± 49 g to 756 ± 55 g, P < .01). Force frequency curves showed improved contractility in the KCI group at stimulation frequencies below 30 Hz. Conclusions: Exogenous increases in blood [K +] potentiate skeletal muscle contraction in intact animals and reverse low-frequency twitch fatigue. A possible mechanism may be the maintenance of intracellular [K +] by hindering K + efflux from skeletal muscle cells.