Abstract:
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.
摘要:
冷冻手术是一种治疗局灶性前列腺癌(PCa)的微创方法。主要并发症是神经血管束(NVB)中海绵状神经的冷冻损伤。这种神经冷冻损伤停止了动作电位(AP)的传导,并最终导致勃起功能障碍,因此降低了患者的生活质量。这里,我们建议将冷冻保护剂(CPA)应用于NVB的神经区域,在前列腺冷冻手术之前,以最小化AP传导的不可恢复损失。我们根据在临床病例中获得的数据对冷冻手术程序进行了建模,并应用了具有NVB温度曲线的离体猪膈神经和大鼠坐骨神经。在CPA暴露之前和之后以及恢复3小时期间测量AP。AP振幅恢复与各种CPA组成的比较表明,某些CPA(例如,5%DMSO+7.5%海藻糖和5%M22用于猪和大鼠神经,分别)显示很少或没有毒性和有效的冷冻保护(平均48%和30%的回收AP,分别)。总之,我们证明,如果正确选择CPA并将其部署到神经上,则暴露于冷冻条件后可以保留神经传导。