Lowe Alexis L, Rivera Santana Maria V, Bopp Taylor, Quinn Kiara N, Johnson Johnnie, Ward Christopher, Chung Tae Hwan, Tuffaha Sami, Thakor Nitish V
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Department of Biology, University of Puerto Rico at Mayagüez, Mayagüez, PR, United States.
Front Physiol. 2024 Feb 15;15:1328520. doi: 10.3389/fphys.2024.1328520. eCollection 2024.
Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery ( = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs ( = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls ( = 0.001). The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation.
肌肉再支配（MR）手术通过获取严重受损的神经并为其提供新的失神经肌肉靶点（DMT），为截肢者带来康复益处。然而，MR手术期间肌肉组织的物理变化对长期功能结果的影响仍未得到充分研究。我们的大鼠后肢MR手术模型利用由外侧腓肠肌（LG）制成的带血管、直接神经化的DMT，我们用它来评估肌肉组织大小对再支配结果的影响，具体是将DMT与横断的腓总神经配对。我们对两组大鼠进行了MR手术，一组是手术时DMT体积完整，另一组是手术时DMT体积部分损失500毫克（每组n = 6），并在再支配100天后测量功能结果。从再支配的DMT记录复合运动动作电位（CMAP）和等长强直力产生，并与对侧未处理的LG肌肉作为阳性对照进行比较。再支配的DMT质量始终低于阳性对照，而部分体积损失的DMT与完整体积的DMT相比，质量没有显著降低（P = 0.872）。再支配的DMT中CMAP振幅平均较低，但无论手术组如何，肌肉质量与最大CMAP振幅之间也存在广泛的线性相关性（R = 0.495）。令人惊讶的是，无论有无体积损失，两个MR组与阳性对照相比均未显示力量下降。两个MR组中，再支配的DMT的平均力量输出占对侧LG力量输出的比例均接近100%，这与我们在术后7天的阴性对照组中观察到的9.6%（±6.3%）的力量输出有显著差异。组织组织学分析显示，除了与阳性对照相比，体积损失的再支配DMT的平均肌纤维面积显著减少外（P = 0.001），几乎没有显著差异。我们的大鼠MR模型结果表明，组织电生理学（CMAP）和运动学（力量产生）可能在不同的时间尺度上恢复，MR手术时的肌肉体积损失在再支配100天后并未显著降低DMT的功能结果测量值。
