TY - JOUR

T1 - Benefits of alpha-ketoglutarate versus succinate on rat muscle dysfunction as a result of exposure to a uremic environment

AU - Bartels, Else M.

AU - Pierzynowski, Stefan G.

AU - Harrison, Adrian Paul

PY - 2007

Y1 - 2007

N2 - Muscle weakness is a prominent feature of end-state renal failure. While the cause of this strongly disabling muscle condition is at present unknown, there are suggestions that metabolic factors may play a role in this type of muscle fatigue. In vitro measurements of muscle function of the fast-twitch extensor digitorum longus (EDL) muscle of adult rats was performed. Isolated muscles were exposed to either a normal ionic environment, a uremic environment - with and without alpha-ketoglutarate (AKG), or with and without succinate, before being field stimulated until they were almost totally fatigued. The addition of AKG to the uremic environment was found to restore muscle performance so that the muscles no longer differed significantly from those incubated in a normal ionic environment. Similar effects to those noted for AKG were observed for succinate. It is concluded that DKG and succinate have a positive and restorative effect on muscle fatigue in uremic fast skeletal muscles in vitro. This beneficial form of treatment is proposed to act at the in vitro isolated muscle level by means of phosphate-binding, as the literature shows that an elevated plasma Pi concentration with renal failure disrupts normal muscle function.

AB - Muscle weakness is a prominent feature of end-state renal failure. While the cause of this strongly disabling muscle condition is at present unknown, there are suggestions that metabolic factors may play a role in this type of muscle fatigue. In vitro measurements of muscle function of the fast-twitch extensor digitorum longus (EDL) muscle of adult rats was performed. Isolated muscles were exposed to either a normal ionic environment, a uremic environment - with and without alpha-ketoglutarate (AKG), or with and without succinate, before being field stimulated until they were almost totally fatigued. The addition of AKG to the uremic environment was found to restore muscle performance so that the muscles no longer differed significantly from those incubated in a normal ionic environment. Similar effects to those noted for AKG were observed for succinate. It is concluded that DKG and succinate have a positive and restorative effect on muscle fatigue in uremic fast skeletal muscles in vitro. This beneficial form of treatment is proposed to act at the in vitro isolated muscle level by means of phosphate-binding, as the literature shows that an elevated plasma Pi concentration with renal failure disrupts normal muscle function.

KW - Former LIFE faculty

KW - uremia

KW - phosphates

KW - succinate

KW - alpha-ketoglutarate

M3 - Journal article

VL - 1

SP - 51

EP - 54

JO - The Journal of Pre-Clinical and Clinical Research

JF - The Journal of Pre-Clinical and Clinical Research

SN - 1898-2395

IS - 1

ER -