Ferguson 2016 J Bioenerg Biomembr
|Ferguson MA, Sutton RM, Karlsson M, Sjövall F, Becker LB, Berg RA, Margulies SS, Kilbaugh TJ (2016) Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction. J Bioenerg Biomembr 48:269-79.|
Abstract: Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics.
The objective was to determine if platelet mitochondrial respiration increases following CA in a porcine pediatric model of asphyxia-associated ventricular fibrillation (VF) CA, and if this readily obtained biomarker is associated with decreased brain mitochondrial respiration. CA protocol: 7 min of asphyxia, followed by VF, protocolized titration of compression depth to systolic blood pressure of 90 mmHg and vasopressor administration to a coronary perfusion pressure greater than 20 mmHg.
Platelet integrated mitochondrial electron transport system (ETS) function evaluated pre- and post-CA/ROSC four hours after return of spontaneous circulation (ROSC). Secondary outcome: correlation of platelet mitochondrial bioenergetics to cerebral bioenergetic function. Platelet maximal oxidative phosphorylation (OXPHOSCI+CII), P < 0.02, and maximal respiratory capacity (ETSCI+CII), P < 0.04, were both significantly increased compared to pre-arrest values. This was primarily due to a significant increase in succinate-supported respiration through Complex II (OXPHOSCII, P < 0.02 and ETSCII, P < 0.03). Higher respiration was not due to uncoupling, as the LEAKCI + CII respiration (mitochondrial respiration independent of ATP-production) was unchanged after CA/ROSC. Larger increases in platelet mitochondrial respiratory control ratio (RCR) compared to pre-CA RCR were significantly correlated with lower RCRs in the cortex (P < 0.03) and hippocampus (P < 0.04) compared to sham respiration. Platelet mitochondrial respiration is significantly increased four hours after ROSC. Future studies will identify mechanistic relationships between this serum biomarker and altered cerebral bioenergetics function following cardiac arrest.
• Keywords: Biomarker, Brain injury, Cardiac arrest, Innate immune response, Mitochondria, Platelets • Bioblast editor: Plangger M • O2k-Network Lab: SE Lund Elmer E, US PA Philadelphia Margulies S, US PA Philadelphia Kilbaugh T
Labels: MiParea: Respiration Pathology: Cardiovascular
Organism: Pig Tissue;cell: Nervous system, Platelet Preparation: Intact cells, Permeabilized cells, Homogenate
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k