Energy Therapeutics: Part II – Tissue Effects

Introduction 

Energy-based therapies interact with the body differently, depending on the type of energy used. In Part I, we explored how these treatments work, the technology behind them, and how they’ve expanded treatment options across various areas of medicine. In Part II, we’ll dive into what happens when these different energies meet human tissue at the cellular level. For doctors and engineers working on next-generation treatments for chronic conditions, this is the foundation of everything they build. When we understand these tissue interactions, we can explain why radiofrequency might be perfect for one application while cryotherapy for another. This deeper knowledge is what drives some of the most exciting innovations in the field today. 

Reversible Electroporation (RE) 

In reversible electroporation, short electric pulses create temporary pores in the cell membrane. These pores allow large molecules like DNA, RNA, or drugs to enter the cell – and here’s the key part – without killing the cell. Once the electric pulses stop, the membrane seals back up, and the cell goes about its business. This makes RE incredibly useful for getting therapeutic agents exactly where we need them.  

The cellular uptake rate using reversible electroporation can be several orders of magnitude higher than conventional delivery methods. This efficiency enables clinicians to use much smaller, more targeted doses to achieve improved therapeutic delivery while minimizing peripheral side effects. This represents a significant advantage for both treatment efficacy and patient outcomes. 

Irreversible Electroporation (IRE) 

IRE (also called Pulsed Field Ablation or PFA) takes the same principle. Instead of creating temporary pores, these higher-voltage pulses blow holes in the cell membrane that never close. 

The cell essentially loses its ability to maintain osmotic balance and literally falls apart. But—and this is super important—IRE doesn’t rely on heat. Traditional ablation techniques cook tissue, which can damage everything nearby. IRE can selectively zap certain cell types while leaving critical structures like nerves relatively unharmed. 

The cell death from IRE isn’t instant. The full effects might take days or even weeks as the body cleans up the mess and remodels the tissue. We’re seeing dramatic results with IRE in cancer treatments, especially when combined with drugs. The one-two punch of weakening cancer cells with IRE and then hitting them with targeted drugs is showing real promise for some of the toughest cancer cases. 

The cardiac electrophysiology world is particularly excited about IRE for arrhythmias. Traditional RF ablation burns tissue, which can cause serious complications. Early clinical data suggests IRE might finally give us a safer alternative. 

Cryoablation 

Cryoablation takes us in a completely different direction – instead of applying heat, we’re freezing tissue. The technology uses probes that circulate argon gas to rapidly cool tissues down to -20°C to -40°C. At these temperatures, something fascinating happens: ice crystals form everywhere – inside cells and in the spaces between them. These crystals aren’t gentle. They physically rupture cell membranes and tear apart the delicate internal structures that keep cells functioning. 

What physicians find particularly valuable about cryoablation is the visual feedback during procedures. Unlike most other energy modalities, the ice ball that forms around the probe tip shows up clearly on imaging. This gives doctors something they rarely get with other techniques – the ability to see exactly what tissue they’re treating in real time. Imagine being able to watch the treatment zone form and adjust as needed to protect vital structures nearby. That kind of precision makes cryoablation especially useful for treating areas where damaging surrounding tissue would cause serious complications. 

Thermal Ablation (Radiofrequency, Microwave, Ultrasound, Laser) 

Thermal approaches represent the original energy therapeutic techniques and remain remarkably effective today. Whether we’re talking about radiofrequency, microwave, ultrasound, or laser applications, they all create similar tissue effects by essentially cooking proteins. 

When tissue temperatures climb above 45-60°C, even for moments, proteins like collagen begin to unravel. Their carefully folded structures come apart, cell nuclei are denatured, and the cellular machinery simply stops working. 

The body’s response to this thermal damage makes these treatments particularly effective. After the initial injury, a complex healing cascade begins. Inflammation arrives first as the body recognizes damaged tissue. Then, specialized cleaning cells called macrophages move in to remove cellular debris, while fibroblasts follow behind, depositing fresh collagen and creating a scaffold for tissue rebuilding. This natural healing response is exactly what we’re trying to trigger for many clinical applications—we’re using controlled damage to stimulate the body’s remarkable repair mechanisms. 

Conclusion 

Each energy modality interacts with tissue in its own unique way. Picking the right tool means understanding exactly how we want to affect the tissue. Are we trying to get drugs into cells? Kill cells directly? Trigger a healing response? The mechanism matters. What’s truly remarkable is how the body responds to these different injuries. It has pre-programmed responses to cellular damage that we can leverage for therapeutic benefit. This is particularly true with thermal injuries, where the cytokine cascade can help remodel and heal tissue. 

We’re seeing incredible breakthroughs in energy therapeutics – new approaches to early-stage cancer, better treatments for cardiac arrhythmias, and novel delivery systems for cell and gene therapy. The more we understand tissue effects, the better we can fine-tune these approaches to help more patients. 

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References 

1. Davalos, R.V., Mir, L.M., Rubinsky, B. (2005). “Tissue ablation with irreversible electroporation.” Annals of Biomedical Engineering, 33(2), 223-231. https://pubmed.ncbi.nlm.nih.gov/15771276/ 
2. Jiang, C., Davalos, R.V., Bischof, J.C. (2015). “A review of basic to clinical studies of irreversible electroporation therapy.” IEEE Transactions on Biomedical Engineering, 62(1), 4-20. https://pubmed.ncbi.nlm.nih.gov/25389236/ 
3. Yarmush, M.L., Golberg, A., Serša, G., Kotnik, T., Miklavčič, D. (2014). “Electroporation-based technologies for medicine: principles, applications, and challenges.” Annual Review of Biomedical Engineering, 16, 295-320. https://pubmed.ncbi.nlm.nih.gov/24905876/ 
4. Chu, K.F., Dupuy, D.E. (2014). “Thermal ablation of tumours: biological mechanisms and advances in therapy.” Nature Reviews Cancer, 14(3), 199-208. https://pubmed.ncbi.nlm.nih.gov/24561446/ 
5. Baust, J.G., Gage, A.A., Bjerklund Johansen, T.E., Baust, J.M. (2014). “Mechanisms of cryoablation: clinical consequences on malignant tumors.” Cryobiology, 68(1), 1-11. https://pubmed.ncbi.nlm.nih.gov/24239684/ 
6. Ahmed, M., Brace, C.L., Lee, F.T., Goldberg, S.N. (2011). “Principles of and advances in percutaneous ablation.” Radiology, 258(2), 351-369. https://pubmed.ncbi.nlm.nih.gov/21273519/ 
7. Reddy, V.Y., et al. (2019). “Pulsed field ablation for pulmonary vein isolation in atrial fibrillation.” Journal of the American College of Cardiology, 74(3), 315-326.https://pubmed.ncbi.nlm.nih.gov/31085321/