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

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Region Hovedstaden - en del af Københavns Universitetshospital

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Publikation: Bidrag til tidsskrift › Tidsskriftartikel › peer review

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Senthil, Kumaran ; Morgan, Ryan W ; Hefti, Marco M ; Karlsson, Michael ; Lautz, Andrew J ; Mavroudis, Constantine D ; Ko, Tiffany ; Nadkarni, Vinay M ; Ehinger, Johannes ; Berg, Robert A ; Sutton, Robert M ; McGowan, Francis X ; Kilbaugh, Todd J. / Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model. I: Resuscitation plus. 2021 ; Bind 6. s. 100124.

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@article{74c79d1ff3eb4aa495ce03aa81836f42,

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

abstract = "Objective: 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.Interventions: 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.Results: 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.Conclusions: 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.Institutional protocol number: IAC 16-001023.",

author = "Kumaran Senthil and Morgan, {Ryan W} and Hefti, {Marco M} and Michael Karlsson and Lautz, {Andrew J} and Mavroudis, {Constantine D} and Tiffany Ko and Nadkarni, {Vinay M} and Johannes Ehinger and Berg, {Robert A} and Sutton, {Robert M} and McGowan, {Francis X} and Kilbaugh, {Todd J}",

note = "{\textcopyright} 2021 The Authors.",

year = "2021",

month = jun,

doi = "10.1016/j.resplu.2021.100124",

language = "English",

volume = "6",

pages = "100124",

journal = "Resuscitation plus",

issn = "2666-5204",

publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

AU - Senthil, Kumaran

AU - Morgan, Ryan W

AU - Hefti, Marco M

AU - Karlsson, Michael

AU - Lautz, Andrew J

AU - Mavroudis, Constantine D

AU - Ko, Tiffany

AU - Nadkarni, Vinay M

AU - Ehinger, Johannes

AU - Berg, Robert A

AU - Sutton, Robert M

AU - McGowan, Francis X

AU - Kilbaugh, Todd J

PY - 2021/6

Y1 - 2021/6

N2 - Objective: 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.Interventions: 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.Results: 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.Conclusions: 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.Institutional protocol number: IAC 16-001023.

AB - Objective: 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.Interventions: 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.Results: 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.Conclusions: 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.Institutional protocol number: IAC 16-001023.

U2 - 10.1016/j.resplu.2021.100124

DO - 10.1016/j.resplu.2021.100124

M3 - Journal article

C2 - 34223382

VL - 6

SP - 100124

JO - Resuscitation plus

JF - Resuscitation plus

SN - 2666-5204

ER -

ID: 72898824