PMID- 38180451 OWN - NLM STAT- MEDLINE DCOM- 20240209 LR - 20240305 IS - 1522-1539 (Electronic) IS - 0363-6135 (Linking) VI - 326 IP - 3 DP - 2024 Mar 1 TI - NADPH oxidase overexpression and mitochondrial OxPhos impairment are more profound in human hearts donated after circulatory death than brain death. PG - H548-H562 LID - 10.1152/ajpheart.00616.2023 [doi] AB - This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups (n = 6) based on different WITs (20, 40, and 60 min). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 h. Left ventricular biopsies were performed at hours 0, 2, 4, and 6. Cardiac stress [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: 47-kDa protein of phagocyte oxidase (p47(phox)), 91-kDa glycoprotein of phagocyte oxidase (gp91(phox))] and mitochondrial oxidative phosphorylation [OxPhos, complex I (NADH dehydrogenase) subunit of ETC (CI)-complex V (ATP synthase) subunit of ETC (CV)] proteins were measured in cardiac tissue and mitochondria respectively. Modulation of cardiac stress and mitochondrial dysfunction were observed in both DCD and DBD hearts. However, DCD hearts suffered more cardiac stress (overexpressed NADPH oxidase subunits) and diminished mitochondrial OxPhos than DBD hearts. The severity of cardiac stress and impaired oxidative phosphorylation in DCD hearts correlated with the longer WIT and subsequent cold storage time. More drastic changes were evident in DCD hearts with a WIT of 60 min or more. Activation of NADPH oxidase via overproduction of p47(phox) and gp91(phox) proteins in cardiac tissue may be responsible for cardiac stress leading to diminished mitochondrial oxidative phosphorylation. These protein changes can be used as biomarkers for myocardium damage and might help assess DCD and DBD heart transplant suitability.NEW & NOTEWORTHY First human DCD heart research studied cardiac stress and mitochondrial dysfunction concerning WIT and the efficacy of del Nido cardioplegia as an organ procurement solution and subsequent cold storage. Mild to moderate cardiac stress and mitochondrial dysfunction were noticed in DCD hearts with WIT 20 and 40 min and cold storage for 4 and 2 h, respectively. These changes can serve as biomarkers, allowing interventions to preserve mitochondria and extend WIT in DCD hearts. FAU - Mondal, Nandan K AU - Mondal NK AUID- ORCID: 0000-0003-2999-8567 AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 AD - Department of Regenerative Medicine Research, Texas Heart Institute, Houston, Texas, United States. FAU - Li, Shiyi AU - Li S AUID- ORCID: 0000-0002-1650-3249 AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 FAU - Elsenousi, Abdussalam E AU - Elsenousi AE AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 FAU - Mattar, Aladdein AU - Mattar A AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 FAU - Nordick, Katherine V AU - Nordick KV AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 FAU - Lamba, Harveen K AU - Lamba HK AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 FAU - Hochman-Mendez, Camila AU - Hochman-Mendez C AD - Department of Regenerative Medicine Research, Texas Heart Institute, Houston, Texas, United States. FAU - Rosengart, Todd K AU - Rosengart TK AD - Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. FAU - Liao, Kenneth K AU - Liao KK AD - Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States. ROR: https://ror.org/02pttbw34 LA - eng GR - Brockman Foundation/ PT - Journal Article DEP - 20240105 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - EC 1.6.3.- (NADPH Oxidases) RN - 0 (Biomarkers) RN - EC 1.- (Oxidoreductases) SB - IM CIN - Am J Physiol Heart Circ Physiol. 2024 Mar 1;326(3):H857-H859. PMID: 38334970 MH - Humans MH - Brain Death MH - *Heart Transplantation MH - Oxidative Phosphorylation MH - Tissue Donors MH - NADPH Oxidases MH - Biomarkers MH - Oxidoreductases MH - *Mitochondrial Diseases MH - Death MH - Retrospective Studies OTO - NOTNLM OT - cardiac stress OT - cold static storage OT - human donor heart OT - mitochondrial oxidative phosphorylation OT - warm ischemic time EDAT- 2024/01/05 12:43 MHDA- 2024/02/09 06:43 CRDT- 2024/01/05 10:43 PHST- 2024/02/09 06:43 [medline] PHST- 2024/01/05 12:43 [pubmed] PHST- 2024/01/05 10:43 [entrez] AID - 10.1152/ajpheart.00616.2023 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2024 Mar 1;326(3):H548-H562. doi: 10.1152/ajpheart.00616.2023. Epub 2024 Jan 5.