Effect of Celsior Cold Storage on Warm Ischemia-Induced Myocardial Plasma Membrane Damage and Pyroptosis in Human Hearts from Circulatory Death Donors.

Celsior solution (CS) is used for cold preservation of hearts from brain death donors but not for those from circulatory death donors (DCD). Plasma membrane repair proteins are crucial for maintaining myocardial integrity during ischemia. We compared the effects of CS cold preservation with normal saline (NS) on myocardial membrane disruption and pyroptosis in human DCD hearts, with varying warm ischemia times (WIT) and cold storage durations. Twenty-four human DCD hearts (WIT≤30, n=12 and WIT>30, n=12) were procured and divided into four groups based on preservation solutions and WIT (n=6/group): (i) NS+WIT≤30 minutes (min), (ii) CS+WIT≤30 min, (iii) NS+WIT>30 min, and (iv) CS+WIT>30 min. All hearts received del Nido cardioplegia before cold storage in CS (n=12) or NS (n=12) for 6 hours. Left ventricular biopsies were performed at 0, 2, 4, and 6 hours to assess myocardial membrane proteins (Annexin A1, Dysferlin, and MG53), calcium levels, pyroptotic proteins (NLRP3, GSDMD-NT), edema, and injury scores. Before cold storage, DCD hearts with a WIT >30 minutes showed impaired membrane integrity, increased pyroptosis, calcium overload, significant edema, and injury. After cold storage, neither normal saline nor Celsior improved myocardial integrity in hearts with a WIT>30 minutes. However, cold Celsior storage did help preserve myocardial membrane integrity and reduce pyroptosis, edema, and injury for up to 4 hours in hearts with a WIT of 30 minutes or less. Celsior effectively preserves DCD hearts with WIT≤30 min for up to 4 hours, highlighting its potential in optimizing DCD heart preservation.