Organ Preservation for Transplant: Techniques & Methods

Goal

Extend viable ex vivo time (ischemia tolerance) while minimizing ischemia-reperfusion injury (IRI). Success = graft function post-transplant.

Preservation Principles

• Hypothermia (0–4°C): Reduces metabolic rate 10–15× (Q10 rule).
• Preservation solution: Impermeants (lactobionate, raffinose) prevent cell swelling; buffers (phosphate, HEPES) maintain pH; antioxidants (glutathione, allopurinol) reduce ROS; energy substrates (adenosine, ketoglutarate).
• Oxygenation: For machine perfusion.

Major Solutions

Solution	Type	Key Components	Primary Use
University of Wisconsin (UW)	Intracellular (high K⁺)	Lactobionate, raffinose, hydroxyethyl starch, glutathione, adenosine, allopurinol	Liver, pancreas, kidney (gold standard)
Histidine-Tryptophan-Ketoglutarate (HTK)	Extracellular (low K⁺, high Na⁺)	Histidine buffer, tryptophan, ketoglutarate, mannitol	Heart, liver, kidney (lower viscosity)
Celsior	Extracellular	Lactobionate, mannitol, glutamate, glutathione	Heart, lung
Perfadex / Low Potassium Dextran	Extracellular	Dextran 40, glucose, buffer	Lung

Preservation Modalities

1. Static Cold Storage (SCS) – Standard

• Organ flushed with cold solution, stored in sterile bag on ice.
• Simple, portable, low cost.
• Limits: heart/lung 4–6h, liver 8–12h, kidney 24–36h, pancreas 12–18h.

2. Hypothermic Machine Perfusion (HMP)

• Continuous pump-driven flow (1–4°C) through organ vasculature.
• Benefits: oxygen/nutrient delivery, waste washout, real-time assessment (flow, resistance).
• Standard for kidneys (↑ graft survival, ↓ DGF). Emerging for liver, heart.

3. Normothermic Machine Perfusion (NMP)

• Near-physiologic temp (35–37°C), oxygenated blood-based perfusate.
• Allows functional assessment (bile production, lactate clearance, metabolism).
• Enables repair, defatting, drug delivery.
• Transforming liver & heart transplantation; expanding donor pool (DCD, marginal).

4. Subnormothermic / Controlled Rewarming

• Intermediate temps (20–25°C) to mitigate cold injury before NMP.

Organ-Specific Considerations

• Heart: Most time-sensitive. NMP (OCS Heart) enables DCD hearts, functional assessment. SCS limit 4h.
• Lung: Perfadex + inflation. EVLP (ex vivo lung perfusion) at normothermia assesses/reconditions marginal lungs.
• Liver: UW/HTK SCS; HMP/NMP for extended criteria/DCD. Bile production = viability marker.
• Kidney: HMP standard for DCD/extended criteria. Pulsatile vs. continuous flow.
• Pancreas/Intestine: UW SCS; sensitive to cold ischemia.

Transport & Logistics

• Dedicated organ procurement organizations (OPOs) coordinate.
• Temperature monitoring (data loggers), GPS tracking.
• Charter flights for distance; commercial cargo with priority.

Emerging Frontiers

• Normothermic regional perfusion (NRP) in DCD donors in situ.
• Gene/RNA therapy during perfusion.
• Cross-circulation (xenogeneic) platforms.
• AI-driven viability prediction from perfusion parameters.

Bottom Line

Preservation has evolved from static cold storage to dynamic, assessed, and reparative machine perfusion. NMP is expanding the donor pool and improving outcomes, especially for marginal organs.