NADPH Oxidase Overexpression and Mitochondrial OxPhos Impairment are More Profound in Human Hearts Donated after Circulatory Death Than Brain Death

This study investigated cardiac stress and mitochondrial oxidative phosphorylation in human DCD (donation after circulatory death) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them to that of human DBD (brain death donor) hearts. A total of 24 human hearts were procured for the research study-six in the DBD group and eighteen in the DCD group. DCD group was divided into three groups (n=6) based on different WITs (20, 40, and 60 minutes). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 hours. Left ventricular biopsies were performed at hours 0,2,4, and 6. Cardiac stress (NADPH oxidase subunits: p47phox, gp91phox) and mitochondrial oxidative phosphorylation (OxPhos: CI-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 minutes or more. Activation of NADPH oxidase via overproduction of p47phox and gp91phox proteins in cardiac tissue may be responsible for cardiac stress leading to diminished mitochondrial oxidative phosp...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research