Succinylcholine-induced fasciculations in denervated rat muscles as measured using 31P-NMR spectroscopy: the effect of pretreatment with dantrolene or vecuronium.

Abstract

We have previously demonstrated by 31P nuclear magnetic resonance (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle. To specify those changes, we attempted to inhibit them using two different kinds of drugs, dantrolene and vecuronium. Three weeks after unilateral sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated denervated muscle group; (3) denervated muscle group pretreated with a low dose of vecuronium (0.02 mg.kg(-1)); (4) denervated muscle group pretreated with a high dose of vecuronium (0.2 mg.kg(-1)); (5) denervated muscle group pretreated with dantrolene (2 mg.kg(-1)). The change of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by 31P-NMR before and after SCh (1 mg.kg(-1)) administration and the corresponding peak amplitude of the electromyograms (EMG) was determined. The high dose of vecuronium totally inhibited SCh-induced fasciculation on EMG (100%-->2%). In this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the peak after 5 min disappeared. The inhibition with dantrolene was about the same order of magnitude as with the low dose of vecuronium (35%:21%). However, the increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs. Our findings indicate that the Pi/PCr increases 5 and 10 min after SCh, respectively, as a result of two different processes. The first peak is caused by an excessive energy consumption in response to excessive muscle contraction. This in turn triggers the second peak, caused by breakdown of glycogen, initiated by an increased Ca2+ concentration.