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Warm Ischemia Limits For Donor Cell Viability In Partial Heart Transplant Grafts
Sujay Sreenivas, MD, Herra Javed, MBBS, Louis Steen, BS, Simon Chung, MS, Alm Kassier, MD, Rodolfo Henrich-Lobo, MD, Craig Porter, PhD, Gabriella ten-Have, PhD, Se-Ran Jun, PhD, Taufiek K. Rajab, MD
University of Arkansas for Medical Sciences, Little Rock, AR
Objectives: Partial heart transplantation (PHT) is the first clinically successful strategy to deliver growing heart valve implants for children. Currently, PHTs are procured according to heart transplant donor protocols. To increase the available donor pool, we hypothesized that tissue donor protocols are sufficient to maintain viability of PHT grafts. AATB Standard D5.400 permits up to 15 cumulative unrefrigerated hours during recovery.
Methods: In a time-course experiment, donor piglets(n=16) were prepared for unrefrigerated PHT graft recovery from 0 to 15 hours following circulatory death. Each tissue component of the PHT grafts (valve leaflet, vessel root suspending the leaflet, and ventricular sewing ring) was examined using cell viability assays, mitochondrial respiration, histology, and multi-omics profiling.
Results: Warm ischemia provoked progressive decay in viability over time (Fig1,p<0.05). Aortic leaflets reached 50% viability loss at 5.4h (95%CI:5.2-5.7), failing faster than pulmonary leaflets (8.9h; 95%CI:8.7-9.0). Respirometry localized a metabolic "tipping point" at 8-hours: grafts recovered >8 hours exhibited Complex I collapse (p<0.01) and pathological succinate surge (p<0.001). Multi-omics confirmed oxidative stress markers diverged from baseline after 8-hours (p<0.05).
Conclusion: PHT grafts tolerate unrefrigerated recovery, but AATB Standard D5.400 exceeds warm ischemia limits for donor cell viability. We propose maximum unrefrigerated recovery of 5-hours for aortic valves and 8-hours for pulmonary valves. These data support a new AATB tissue procurement standard specifically for PHTs.
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