Effect of cold storage solution on warm ischemia-induced myocardial plasma membrane damage and pyroptosis in human hearts from circulatory death donors.

Abstract

Celsior solution (CS) (IGL Group) 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 minutes [n = 12] and WIT >30 minutes [n = 12]) were procured and divided into 4 groups based on preservation solutions and WIT (n = 6 per group): NS + WIT ≤30 minutes, CS + WIT ≤30 minutes, NS + WIT >30 minutes, and CS + WIT >30 minutes. All hearts received del Nido cardioplegia before cold storage in CS (n = 12) or NS (n = 12) for 6 hours. Left ventricle biopsies were performed at 0, 2, 4, and 6 hours to assess myocardial membrane proteins (annexin A1, dysferlin, and mitsugumin 53), calcium levels, pyroptotic proteins (NACHT, LRR, and PYD domains-containing protein 3 and gasdermin D, N-terminal fragment), 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 CS improved myocardial integrity in hearts with a WIT >30 minutes. However, cold CS 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. CS effectively preserves DCD hearts with WIT ≤30 minutes for up to 4 hours, highlighting its potential in optimizing DCD heart preservation.