Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

• DOI: 10.1016/j.resplu.2021.100124
• Publication Date: 2021-04-30T01:53:24Z
• Authors: Kumaran Senthil; Ryan W. Morgan; Marco M. Hefti; Michael Karlsson; Andrew J. Lautz; Constantine D. Ma...; Tiffany Ko; Vinay M. Nadkarni; Johannes Ehinger; Robert A. Berg; Robert M. Sutton; Francis X. McGowan; Todd J. Kilbaugh
• Keywords: Cardiopulmonary resuscitation; Fission; 0303 health sciences; 03 medical and health sciences; RC581-951; Specialties of internal medicine; Cardiac arrest; Fusion; Mitochondria; Dynamics; Experimental Paper

Cerebral mitochondrial dysfunction is a key mediator of neurologic injury following cardiac arrest (CA) and is regulated by the balance of fusion and fission (mitochondrial dynamics). Under stress, fission can decrease mitochondrial mass and signal apoptosis, while fusion promotes oxidative phosphorylation efficiency. This study evaluates mitochondrial dynamics and content in brain tissue 24 h after CA between two cardiopulmonary resuscitation (CPR) strategies.Piglets (1 month), previously randomized to three groups: (1) Std-CPR (n = 5); (2) HD-CPR (n = 5; goal systolic blood pressure 90 mmHg, goal coronary perfusion pressure 20 mmHg); (3) Shams (n = 7). Std-CPR and HD-CPR groups underwent 7 min of asphyxia, 10 min of CPR, and standardized post-resuscitation care. Primary outcomes: (1) cerebral cortical mitochondrial protein expression for fusion (OPA1, OPA1 long to short chain ratio, MFN2) and fission (DRP1, FIS1), and (2) mitochondrial mass by citrate synthase activity. Secondary outcomes: (1) intra-arrest haemodynamics and (2) cerebral performance category (CPC) at 24 h.HD-CPR subjects had higher total OPA1 expression compared to Std-CPR (1.52; IQR 1.02-1.69 vs 0.67; IQR 0.54-0.88, p = 0.001) and higher OPA1 long to short chain ratio than both Std-CPR (0.63; IQR 0.46-0.92 vs 0.26; IQR 0.26-0.31, p = 0.016) and shams. Citrate synthase activity was lower in Std-CPR than sham (11.0; IQR 10.15-12.29 vs 13.4; IQR 12.28-15.66, p = 0.047), but preserved in HD-CPR. HD-CPR subjects had improved intra-arrest haemodynamics and CPC scores at 24 h compared to Std-CPR.Following asphyxia-associated CA, HD-CPR exhibits increased pro-mitochondrial fusion protein expression, preservation of mitochondrial mass, improved haemodynamics and superior neurologic scoring compared to Std-CPR.IAC 16-001023.