Organ transplantation requires maintaining the viability of a donor organ during the period between its recovery and placement into a recipient. This period, known as the ex vivo time, is a sensitive window where the organ is deprived of its natural blood and oxygen supply. The primary goal of preservation techniques is to slow the biological processes that lead to irreversible cellular damage. By controlling the organ’s environment outside the body, medical teams maintain the tissue’s structure and function, ensuring it remains capable of working once transplanted. Successfully managing this time window allows for necessary logistical steps, such as tissue matching and organ transport, to take place before the procedure.
The Biological Necessity for Preservation
The moment an organ’s blood supply is interrupted, its cells suffer from a lack of oxygen and nutrients, a damaging process termed ischemia. Damage occurs in two phases: warm ischemia and cold ischemia. Warm ischemia is the time the organ remains at body temperature without blood flow, typically occurring before the organ is flushed and cooled. This initial oxygen deprivation at 37°C rapidly depletes the cell’s primary energy source, adenosine triphosphate (ATP).
Cold ischemia begins once the organ is chilled and stored. The fundamental principle of preservation is hypothermia, cooling the organ to temperatures near 4°C. This drop in temperature slows the cellular metabolic rate by approximately 12-fold, dramatically reducing the cells’ demand for oxygen and energy. Since metabolism is not completely halted, energy reserves are gradually consumed, limiting the total storage time. The preservation method must manage both the rapid injury from warm ischemia and the slower, cumulative damage from cold ischemia to prepare the organ for the final step of reperfusion into the recipient.
Static Cold Storage: The Traditional Approach
Static Cold Storage (SCS) has been the standard preservation method for decades due to its simplicity and low cost. The process begins immediately after the organ is removed, when it is flushed with a specialized preservation solution. This initial flushing removes residual blood, introduces the protective solution, and rapidly cools the organ to the target temperature of 4°C.
Preservation solutions, such as the University of Wisconsin (UW) solution or Histidine-Tryptophan-Ketoglutarate (HTK), are complex, engineered fluids designed to protect cells during hypothermia. They balance electrolytes, buffer pH, and contain impermeable molecules to prevent cell swelling, a common consequence of cooling. This composition prevents the influx of water and counteracts the buildup of acidic byproducts from diminished cellular metabolism.
After flushing, the organ is sealed in sterile bags and placed in an insulated container with ice. The organ remains static throughout storage, relying solely on the protective solution and low temperature to suppress cellular activity. While effective for short-term preservation, the complete lack of oxygen and active circulation limits the safe storage time, especially for sensitive organs.
Dynamic Preservation: Utilizing Machine Perfusion
Dynamic preservation, or machine perfusion, represents a significant advancement over static cold storage. This technique connects the organ to a specialized machine that actively pumps a fluid, or perfusate, through its vascular network. This continuous circulation provides a more controlled and protective environment than simply submerging the organ in cold solution.
Machine perfusion is categorized by the temperature at which it operates.
Hypothermic Machine Perfusion (HMP)
HMP maintains the organ at cold temperatures, typically between 4°C and 12°C, while continuously delivering a cold perfusate. This active pumping washes away metabolic waste products that accumulate during ischemia and ensures uniform cooling of the tissue. For kidneys, HMP reduces the risk of delayed graft function compared to static cold storage, leading to better early outcomes.
Normothermic Machine Perfusion (NMP)
NMP preserves the organ at near-body temperature, around 37°C. At this physiological temperature, the perfusate is often an oxygen-carrying solution, sometimes containing red blood cells and nutrients, allowing the organ to maintain metabolic activity. The primary advantage of NMP is the ability to assess the organ’s function in real-time by monitoring markers like bile production or glucose metabolism before transplantation. NMP also provides an opportunity to potentially repair or condition damaged organs, expanding the pool of usable donor organs.
Organ-Specific Preservation Timelines
The maximum time an organ can be safely preserved outside the body, known as the cold ischemic time, varies dramatically based on its sensitivity to ischemia and hypothermia. Organs with high metabolic demands have the shortest preservation windows.
The heart and lungs are the most sensitive organs, limited to a cold ischemic time of four to six hours. The liver and pancreas have slightly longer timelines, generally remaining viable for eight to twelve hours under static cold storage. These constraints dictate transplantation logistics, often requiring the recipient to be ready for surgery before the organ is procured.
In contrast, the kidney is the most resilient organ and tolerates significantly longer preservation times. Kidneys typically remain viable for 24 to 36 hours, allowing for broader sharing and more extensive tissue matching across greater geographic distances. The variation in these limits directly impacts the transplant process, making the location of the donor and recipient a more pressing concern for heart transplants than for kidney transplants.