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.
Original language | English (US) |
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Pages (from-to) | 538-549 |
Number of pages | 12 |
Journal | Annals of Biomedical Engineering |
Volume | 51 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2023 |
Bibliographical note
Funding Information:Porcine nerves were isolated and donated from animals used in other studies from Visible Heart Laboratories (PI: Paul A. Iaizzo). Rat sciatic nerves were donated from animals used in other studies from the laboratory of Professor Erik Finger. All animal handling and treatment prior to nerve extraction was in compliance with approved IACUC protocols at the University of Minnesota. Computational work was conducted at the University of Minnesota Supercomputing Institute. Viscosity measurements were conducted at Polymer Characterization Facility at the University of Minnesota. The authors thank Bat-Erdene Namsrai for handling the animals, Lakshya Gangwar for technical support of the cryostage, Elliott Magnuson for CPA preparation, Dan Voce for helpful discussion and Susan Everson for writing support. This work is funded by Medical Immersion Technology (MIT) Sàrl.
Publisher Copyright:
© 2022, The Author(s) under exclusive licence to Biomedical Engineering Society.
Keywords
- Action potential
- Cryoinjury
- Cryoprotection
- Erectile dysfunction
- Focal therapy
- Neural conduction
- Neurovascular bundle