Ischemia and Reperfusion Injury in Donation after Circulatory Death Heart: Role of Interleukin-1

• Published in: The Journal of heart and lung transplantation Vol. 39; no. 4; p. S134
• Main Authors: Quader, M., Kenning, K., Mezzaroma, E., Toldo, S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2020
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2020.01.1041

Donation after circulatory death donors (DCD) can increase the number of donors for heart transplantation, which currently depends on brain death donors (DBD) only. The DCD process induces substantial ischemia and reperfusion (I/R) injury mediated through cytokines. Interleukin-1 (IL-1) is one of the key downstream effectors of I/R injury. We hypothesize that genetic deletion of IL-1 type I receptor (lL-1RI-/-) or pharmacological inhibition of IL-1 with recombinant IL-1 receptor antagonist (IL-1Ra) may limit I/R injury in DCD hearts.
Four groups of mice were studied, DBD wild type (DBD-WT), DCD-WT, DCD-IL-1RI-/-, and DCD-IL-Ra (n = 8 each). In anesthetized mice, clinical DCD process was simulated with preset warm ischemia time of 40minutes. In DBD group, hearts were procured without ischemia and served as controls. All hearts were reanimated for 90 minutes on a Langendorff system with oxygenated Krebs-Henseleit buffer at steady 76mmHg pressure at 37°C. Heart rate, developed pressure (DP), +dP/dt and -dP/dt were measure as functional parameters. Cardiac troponin I (cTnI) was measured in the eluate as marker of cardiac injury.
Heart rate was higher in all the DCD groups (see table). DP, + and -dP/dt were significantly reduced in DCD-WT compared to DBD group (all p<0.05). Genetic deletion of IL-1RI was protective from DCD I/R injury with low cTnI release and preserved heart function (all p<0.05). Pharmacologic blockage of IL-1 afforded protection from I/R injury in DCD hearts, but the physiologic parameters did not attain statistical significance.
IL-1 contributes to the I/R injury associated with the DCD process. Pharmacologic blockade of IL-1 has a potential to limit I/R injury and preserve function in DCD hearts.