Cardiology

Targeting the NLRP3-inflammasome to reduce warm ischemic injury in donation after circulatory death heart.


Targeting the NLRP3-inflammasome to reduce warm ischemic injury in donation after circulatory death heart.

Clin Transplant. 2020 Jul 12;:e14044

Authors: Quader M, Mezzaroma E, Kenning K, Toldo S

Abstract
While the donation after circulatory death (DCD) heart transplantation is an emerging clinical practice, the primary source of donor hearts for transplantation remains donation after brain death (DBD) donors. DCD process induces formation of NOD-Like Receptor Family Pyrin Domain Containing-3 (NLRP3)-inflammasome, a key mediator of inflammation-driven damage to heart. Inhibition of NLRP3-inflammasome formation could be protective to DCD hearts. Five groups (n=8 each) of mice were studied- control beating heart donor (CBD) wild type (WT), DCD-WT, CBD-NLRP3 knock out (KO), DCD-NLRP3-KO, and DCD-WT-NLRP3 inhibitor group. Hearts were procured and reanimated on a Langendorff system to assess physiologic parameters, then for molecular assays. NLRP3 inhibitor (50ยต mol/L) was administered to the DCD-NLRP3 inhibitor group at reanimation. Tissue NLRP3 levels were 80% higher in the DCD-WT group compared to the CBD-WT group. Caspase-1 activity was significantly elevated in DCD-WT but not in KO or NLRP3 inhibitor groups. The developed pressures, +/- dP/dt were significantly impaired in the DCD-WT group compared to the CBD-WT group, p=<0.05, but were well preserved in DCD-NLRP3 Inhibitor group. The DCD process activates the NLRP3-inflammasome, contributing to myocardial damage and dysfunction. NLRP3-inflammasome inhibition limits myocardial injury and preserves DCD heart function.

PMID: 32654189 [PubMed – as supplied by publisher]

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