Effects of chronic sepsis on contractile properties of fast twitch muscle in an experimental model of critical illness neuromyopathy in the rat

Objective: Critical illness polyneuromyopathy has been extensively studied in various animal models regarding electrophysiological aspects or molecular mechanisms involved in its physiopathology; however, little data are available on its main clinical feature, that is, muscular weakness. We have studied the effects of chronic sepsis in rats with special consideration to contractile and neuromuscular blockade properties in relation with the level of messenger RNA (mRNA) coding for ryanodine and acetylcholine receptors. Design: This was an experimental animal study. Setting: This study was conducted at a university laboratory. Subjects: Subjects consisted of Wistar rats. Interventions: Chronic sepsis was achieved by cecal ligation and needle perforation. Ten days after surgery, fast twitch extensor digitorum longus was excised for extraction and assays of mRNA coding for ryanodine and acetylcholine receptor subunits and contralateral muscle was tested in vivo on a mechanical bench. A fatigability index was measured and neuromuscular blockade properties using atracurium were evaluated. Measurements and Main Results: A decrease in active force developed by extensor digitorum longus associated with an increase in passive force is induced by chronic sepsis. Maximal force at optimal length during twitch contraction was significantly reduced (0.25 ± 0.09 N vs. 0.17 ± 0.06 N); contraction and relaxation speeds were higher as shown by the decrease of respective time constants (3.75 ± 0.01 msec vs. 2.70 ± 0.0 msec, 10.76 ± 0.03 msec vs. 7.62 ± 0.03 msec) in the control group compared with the septic group. Fatigability index was significantly lower (23 ± 0.11% vs. 59 ± 0.19%) in septic rats. These rats also showed quicker blockade and shorter recovery after atracurium administration. Sepsis induced a significant increase of the expression of ryanodine receptor (RyR) RyR1 along with a steady expression of RyR3 mRNA, leading to a 5.6-fold increase of RyR1/RyR3 ratio with a steadiness of mRNA corresponding to acetylcholine-receptors. Conclusions: Chronic inflammation and sepsis induced a decrease in contractile performances of extensor digitorum longus along with accelerated kinetics of atracurium possibly induced by modified expression of RyR1 receptors and not acetylcholine-receptors.