Korean J Physiol Pharmacol.  2014 Dec;18(6):461-467. 10.4196/kjpp.2014.18.6.461.

Streptozotocin Diabetes Attenuates the Effects of Nondepolarizing Neuromuscular Relaxants on Rat Muscles

Affiliations
  • 1Department of Anesthesiology, The Affiliated First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China. bravespirit.li@gmail.com

Abstract

The hypothesis of this study was that diabetes-induced desensitization of rat soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We tested the different magnitude of resistance to vecuronium, cisatracurium, and rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations from rats after 4 and 16 weeks of STZ treatment. The concentration-twitch tension curves were significantly shifted from those of the control group to the right in the diabetic groups. Concentration giving 50% of maximal inhibition (IC50) was larger in the diabetic groups for all the NDMRs. For rocuronium and cisatracurium in both SOL and EDL, IC50 was significantly larger in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL, the IC50 ratios were significantly largest in the diabetic 16 weeks group, second largest in the diabetic 4 weeks group, and smallest for the control group. Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and on the different kind of muscles observed while was independent on different kind of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16 versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL, diabetes attenuated the actions of neuromuscular blockade more intensely than that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not relevant for the kind of NDMRs.

Keyword

Diabetes; Extensor digitorum longus; Non-depolarizing muscle relaxants; Soleus; Streptozotocin

MeSH Terms

Animals
Diabetes Mellitus, Experimental*
Inhibitory Concentration 50
Muscles*
Neuromuscular Blockade
Neuromuscular Junction
Neuromuscular Nondepolarizing Agents
Rats*
Streptozocin
Vecuronium Bromide
Neuromuscular Nondepolarizing Agents
Streptozocin
Vecuronium Bromide

Figure

  • Fig. 1 Twitch tension height elicited by indirect stimulation in Extensor digitorum longus (EDL, A) and Soleus (SOL, B). There was a significant difference between diabetic groups and the age-matched control groups (p<0.05), and between dia 4 wk and dia 16 wk groups (p<0.05), while no significant difference between con 4 wk group and con 16 wk group. *p<0.05 versus control groups, &p<0.05 versus diabetic 4 weeks group. con 4 wk, control 4 weeks group; dia 4 wk, diabetic 4 weeks group; con 16 wk, control 16 weeks group; dia 16 wk, diabetic 16 weeks group.

  • Fig. 2 Concentration-twitch tension curves for rocuronium, vecuronium, and cisatracurium in EDL (A) and SOL (B) in normal rats. The twitch tension was elicited by indirect stimulation at 0.1 Hz. The concentration-twitch tension curves were significantly different (p<0.05).Values are mean±SD (n=10 each). *p<0.05 versus control value of twitch tension for rocuronium, #p<0.05 versus control value for vecuronium, and &p<0.05 versus control value for cisatracurium. EDL, Extensor digitorum longus; SOL, Soleus.

  • Fig. 3 Concentration-twitch tension curves for rocuronium (A, D), vecuronium (B, E), and cisatracurium (C, F). The twitch tension was elicited by indirect stimulation at 0.1 Hz. Values are expressed as mean±SD (n=10 each). The concentration-twitch tension curves of these groups were significantly different for each NDMRs compared with that of control value (p<0.05, data not presented here). For rocuronium (A, D), vecuronium (B, E), and cisatracurium (C, F), there was a significantly difference between the curves in the dia 4 wk or dia16wk group and those in control group (p<0.05). For rocuronium (A, D), vecuronium (B, E), and cisatracurium (F), there was a significantly difference between the curves in the dia4wk group and those in dia 16 wk group (p<0.05). But there was not significantly difference between the curves in the dia 4 wk group and those in dia 16 wk group for cisatracurium in EDL (p>0.05). *p<0.05 versus con group, &p<0.05 versus dia 4 wk group. EDL, Extensor digitorum longus; SOL, Soleus; con, control group; dia 4 wk, diabetic 4 weeks group; dia 16 wk, diabetic 4 weeks group.


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