Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction
Ferguson, Michael A ; Sutton, Robert M ; Karlsson, Michael LU ; Sjövall, Fredrik LU
; Becker, Lance B
; Berg, Robert A
; Margulies, Susan S
and Kilbaugh, Todd J
(2016)
In Journal of Bioenergetics and Biomembranes
48(3).
p.269-279
- Abstract
Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics.
OBJECTIVE: 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.
PRIMARY OUTCOME: platelet integrated mitochondrial electron transport system (ETS) function evaluated... (More)
Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics.
OBJECTIVE: 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.
PRIMARY OUTCOME: 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.
(Less)
- author
- Ferguson, Michael A
; Sutton, Robert M
; Karlsson, Michael
LU
; Sjövall, Fredrik
LU
; Becker, Lance B
; Berg, Robert A
; Margulies, Susan S
and Kilbaugh, Todd J
- organization
- publishing date
- 2016-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Bioenergetics and Biomembranes
- volume
- 48
- issue
- 3
- pages
- 269 - 279
- publisher
- Springer
- external identifiers
-
- scopus:84961589383
- wos:000377022700009
- pmid:27020568
- ISSN
- 1573-6881
- DOI
- 10.1007/s10863-016-9657-9
- language
- English
- LU publication?
- yes
- id
- d3125045-b4c1-4f31-a270-fabbe97f7bd6
- date added to LUP
- 2016-04-18 12:31:35
- date last changed
- 2024-04-04 18:35:18
@article{d3125045-b4c1-4f31-a270-fabbe97f7bd6,
abstract = {{<p>Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics.</p><p>OBJECTIVE: 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.</p><p>PRIMARY OUTCOME: 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.</p>}},
author = {{Ferguson, Michael A and Sutton, Robert M and Karlsson, Michael and Sjövall, Fredrik and Becker, Lance B and Berg, Robert A and Margulies, Susan S and Kilbaugh, Todd J}},
issn = {{1573-6881}},
language = {{eng}},
number = {{3}},
pages = {{269--279}},
publisher = {{Springer}},
series = {{Journal of Bioenergetics and Biomembranes}},
title = {{Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction}},
url = {{http://dx.doi.org/10.1007/s10863-016-9657-9}},
doi = {{10.1007/s10863-016-9657-9}},
volume = {{48}},
year = {{2016}},
}