Piel 2023 MiP2023
| Effect of dimethyl fumarate on cerebral mitochondrial metabolism in a porcine model of pediatric in-hospital cardiac arrest. |
Link: MiP2023 Obergurgl AT
Piel Sarah (2023)
Event: MiP2023 Obergurgl AT
Introduction: Despite advancements in cardiopulmonary resuscitation (CPR), secondary neurological injury remains the key determinant of successful recovery from cardiac arrest (CA) [1-3]. Currently, there are no established clinical therapies that preserve neurological function [4]. We previously found that acute decline in mitochondrial health up to 24 hours post-CA correlated with poor neurological outcome [5-6]. Here, we tested the potential of dimethyl fumarate (DMF), a derivative of the TCA-cycle intermediate fumaric acid shown to enhance mitochondrial bioenergetics [7], to improve mitochondrial injury in brain and heart following successful resuscitation after CA.
Methods: Female piglets representing toddler age underwent asphyxia, followed by ventricular fibrillation, cardiopulmonary resuscitation and defibrillation until return of spontaneous circulation. Subsequently, animals received daily treatment with DMF or vehicle. Sham animals underwent identical anesthesia protocols and instrumentation without CA. After 4 days, animals (n=5 of each group) were euthanized, tissues were harvested and their mitochondrial function, quantity and proteomic profile was analyzed.
Results and discussion: Mitochondrial content and function, as measured by citrate synthase activity and high-resolution respirometry, was reduced at 4 days following CA. In contrast, myocardial mitochondria demonstrated a complete restoration of mitochondrial content and function despite persistent changes in mitochondrial ultrastructure. DMF treatment prevented 25% of the long-term proteomic changes in the brain, including proteins related to mitochondrial bioenergetics and oxidative stress. In addition, myocardial mitochondrial morphology was normalized by DMF. In this model of CA, mitochondria sustained persistent damage in an organ-specific manner. DMF partially prevents these long-term mitochondrial changes in myocardium and brain.
• Keywords: cardiac arrest, mitochondria, dimethyl fumarate, emergency medicine, metabolism
• O2k-Network Lab: DE Duesseldorf Westenfeld R, US PA Philadelphia Kilbaugh T
Labels: Pathology: Cardiovascular
Organism: Pig Tissue;cell: Heart, Nervous system
Event: E2
