Cryopreserved Hearts Can Recover Function upon Thawing

A new study has demonstrated the feasibility of recovering function, structural integrity, and energy production in isolated rat hearts after freezing and then thawing the organ.

Researchers at the Hadassah-Hebrew University Medical Center (Jerusalem, Israel) isolated rat hearts that were subsequently attached to a Langendorff apparatus. After normothermic perfusion, cold cardioplegia was induced followed by perfusion with a cryoprotecting agent. The hearts were than frozen to -8 ºC for 45 minutes, thawed, and reperfused for 60 minutes. Upon examination, all frozen and thawed hearts regained normal electric activity. At -8 ºC, mean ice content was 64.36%. The use of 10% ethylene glycol for cryoprotection resulted in mean recovery of 49.7% of positive ventricular pressure derivative over time (+dP/dt), 48.0% of negative ventricular pressure derivative over time (-dP/dt), 65.2% of coronary flow, and 50.4% of left ventricular developed pressure. Hearts in this group maintained 81.3% viability compared with 69.3% in control hearts kept at 0 ºC for the same duration. Energy stores--represented by adenosine triphosphate (ATP) and phosphocreatine--were depleted to 12.2 micromol/g and 22.5 micromol/g, respectively, compared with 19.0 micromol/g and 36.6 micromol/g respectively in the control hearts. The integrity of muscle fibers and intracellular organelles after thawing and reperfusion was demonstrated by electron microscopy. The study was published in the March 2008 issue of the Journal of Thoracic and Cardiovascular Surgery.

The technology, developed by Core Dynamics (Rockville, MD, USA), involves a dimensional freezing technique to control the proliferation of ice crystallization. The new method allows recovery of function of the intact rat heart after freezing to -8 ºC, a temperature at which 60% of the tissue water is frozen. The process is currently being utilized in the preservation of osteochondral plugs with live cartilage cells to treat knee lesions in Eastern European patients. The company also has work underway to evaluate the freezing and recovery of ovaries, coronary arteries, and various types of cells.

"These results are very encouraging,” said lead author Professor Amir Elami, M.D., of the department of cardiothoracic surgery at Hadassah. "We believe that this achievement will lead to a time when we can bank cryopreserved organs in well-managed organ banks, and have ample time to assure we have the best match for the most critical-need patients.”

One of the most difficult issues for patients needing organ transplants is the tremendous shortage of donor organs. With the donation of a human heart, a healthcare provider is restricted to only a few hours of harvest, transport, and transplant time, which precludes donor-recipient matching between remote locations. This creates a risk of immunological mismatches and increases the likelihood of organ rejection. The ability to prolong the shelf life of donated organs would allow time for improved donor-recipient immunological matching, helping to decrease rejection rates and reduce the intensity of immunosuppression treatments after transplantation.


Related Links:
Hadassah-Hebrew University Medical Center
Core Dynamics