An investigation into the mechanism of action of almitrine on isolated rat diaphragm muscle fatigue.
BACKGROUND
Previous studies have shown that almitrine bismesylate, a respiratory stimulant which acts on the mitochondrial electron transport chain, enhances recovery of rat diaphragm muscle from fatigue.


OBJECTIVE
Our aim is to investigate if the enhanced recovery is due to an anti-oxidant property of almitrine, since the electron transport chain is a major site of intracellular free radical production.


METHODS
A low-frequency fatigue protocol was used (30 Hz; 250 ms; delivered once every 2 s for 5 min), and the effects of almitrine before and after fatigue onset were compared to those of the anti-oxidant compound N-acetylcysteine (NAC).


RESULTS
Almitrine (6 and 10 microg/ml) given before fatigue gave better recovery rates than postfatigue application. In contrast, NAC (100 microM) application before fatigue onset was not as effective as NAC given immediately after the cessation of the fatigue protocol. However, almitrine (6 microg/ml) completely reversed the reduction in baseline twitch tension brought about by a free-radical-producing mixture of FeCl(3) + ADP (1 mM + 2.5 mM, respectively).


CONCLUSIONS
The results of this study confirm that almitrine enhances recovery from fatigue and, in contrast to NAC prefatigue application, is more effective. Also, almitrine was shown to have an anti-oxidant effect, but it does not act like a typical anti-oxidant.
Markos
F
F
Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, National University of Ireland, Dublin, Ireland. hazim@ucc.ie
Campion
D P
DP
Carey
M
M
O'Connor
J J
JJ
D015765:Almitrine / Q000494:pharmacology*; D000818:Animals; D003964:Diaphragm; D066298:In Vitro Techniques; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012132:Respiratory Muscles / Q000187:drug effects* / Q000502:physiology; D019141:Respiratory System Agents / Q000494:pharmacology*
D019141:Respiratory System Agents; D015765:Almitrine