Supercharge End-to-Side Transfer Resuscitates Neuromuscular Junction Recovery in Target Muscles After Prolonged Ischemia
Angela Chien-Yu Chen, MD, Johnny Chuieng- Yi Lu, MD and Eve Huang, MS, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Introduction: Ischemic myopathy is a devasting situation that can lead to permanent loss of muscle function, and subsequent limb contracture due to fibrotic changes. Prolonged muscle ischemia without detection results in irreversible morphologic changes in the neuromuscular junction (NMJ). Similar phenomenon can also be seen with free muscle transfers that shows little recovery after prolonged arterial ischemia. As such, the first aim of the study is to investigate the degree of NMJ morphological changes and resulting function after various time points of prolonged ischemia in muscles downstream from a nerve cut-and-repair model. The second aim is to investigate if supercharge end to side (SETS) from an adjacent donor nerve can salvage the loss of function after ischemia.
Materials and Methods: In the first aim, a mice forelimb ischemia model was used by first temporarily ligating the brachial artery for a set time (Control, 4, 8, 12, 24 hours), combined with median nerve cut and repair and permanently cutting the ulnar nerve. In the second aim, SETS was performed by transferring the proximal ulnar nerve stump into the distal median nerve. Functional recovery was measured by grip test and electrophysiological study. The forelimb flexor muscles were stained with ß-III Tubulin and bungarotoxin for innervation pattern (full / partial / no innervated motor end plates).
Results: With increasing ischemic time, there is decrease in CMAP and grip strength. NMJ reinnervation was significantly worst at 12 and 24 hours with only 39% and 26% fully innervated NMJ (p<0.05), while at 4 and 8 hours it was 72% and 67% (not significantly worse than control at 81%) (Figure 1). The addition of SETS provided significant increase in CMAP for all groups, especially in the 12 and 24 hours ischemia group. SETS did not increase % of full innervation, but increased the % of partially innervated NMJ especially for 12 and 24 hours ischemia (Figure 2).
Conclusion: SETS to the innervating nerve of an ischemic muscle provides potential therapeutic benefits to target muscle characterized by increase in the % of partially innervated NMJ.
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