Department of Mechanical Engineering, University of Minnesota, 111 Church Street SE, Minneapolis, MN, 55455, USA.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, USA.
Ann Biomed Eng. 2023 Mar;51(3):538-549. doi: 10.1007/s10439-022-03059-z. Epub 2022 Sep 10.
Cryosurgery is a minimally invasive approach to the treatment of focal prostate cancer (PCa). A major complication is the cryoinjury to the cavernous nerve in the neurovascular bundle (NVB). This nerve cryoinjury halts conduction of action potentials (APs) and can eventually result in erectile dysfunction and therefore diminished quality of life for the patient. Here, we propose the application of cryoprotective agents (CPA) to the regions of the nerves in the NVB, prior to prostate cryosurgery, to minimize non-recoverable loss of AP conduction. We modeled a cryosurgical procedure based on data taken during a clinical case and applied ex-vivo porcine phrenic nerves and rat sciatic nerve with temperature profile of NVB. The APs were measured before and after the CPA exposures and during 3 h of recovery. Comparisons of AP amplitude recovery with various CPA compositions reveal that certain CPAs (e.g., 5% DMSO + 7.5% Trehalose and 5% M22 for porcine and rat nerves, respectively) showed little or no toxicity and effective cryoprotection from freezing (on average 48% and 30% of recovered AP, respectively). In summary, we demonstrate that neural conduction can be preserved after exposure to freezing conditions if CPAs are properly selected and deployed onto the nerve.
冷冻手术是一种治疗局限性前列腺癌（PCa）的微创方法。一个主要的并发症是在神经血管束（NVB）的海绵体神经中发生的冷冻损伤。这种神经冷冻损伤会阻止动作电位（AP）的传导，并最终导致勃起功能障碍，从而降低患者的生活质量。在这里，我们建议在前列腺冷冻手术前，将冷冻保护剂（CPA）应用于 NVB 中的神经区域，以最大程度地减少不可恢复的 AP 传导损失。我们根据临床病例中获得的数据模拟了冷冻手术过程，并应用了体外猪膈神经和大鼠坐骨神经以及 NVB 的温度曲线。在 CPA 暴露前后以及 3 小时恢复期间测量了 AP 幅度恢复情况。对各种 CPA 成分的 AP 幅度恢复比较表明，某些 CPA（例如，分别为 5％DMSO + 7.5％海藻糖和 5％M22 的猪和大鼠神经）显示出很少或没有毒性，并且可以有效地防止冷冻损伤（平均分别为 48％和 30％的 AP 恢复）。总之，如果正确选择和应用于神经，则可以在暴露于冷冻条件后保留神经传导。
