Polyethylene glycol-20k reduces post-resuscitation cerebral dysfunction in a rat model of cardiac arrest and resuscitation: A potential mechanism

Introduction: Mitochondrial dysfunction from global ischemic-reperfusion (I/R) injury is a major contributor to post-resuscitation myocardial dysfunction. Polyethylene Glycol-20k (PEG-20k) shortens the no-flow phenomenon and improves microcirculation while MCC950 selectively inhibits activation of the NLRP3-inflammasome ensuing pyroptosis. We evaluated the effect of combined therapy with PEG-20k and MCC950 on myocardial mitochondrial function as measured by electron transport chain complex respiration in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Methods: 30 Sprague-Dawley rats weighing between 450-550 g were randomized into five groups (n=6): (1) sham (S); (2) control (C); (3) PEG-20k (P); (4) MCC950 (M); (5) combined (P&M). Ventricular fibrillation (VF) was electrically induced and untreated for 6min, followed by 8min CPR. Resuscitation was attempted with a 4J defibrillation. 2mL P was infused over 2 min at the beginning of CPR, while M (10mg/kg) was administered intraperitoneal (IP) immediately after return of spontaneous circulation (ROSC). At ROSC 6hr, 100mg of heart was harvested, transferred directly into ice-cold K medium (1mL), and homogenized to obtain a 10% homogenate. Homogenates (50μL) were transferred to calibrated Oxygraph-2 chambers. Mitochondrial function was measured using high resolution respirometry. Oxygen flux was corrected and expressed by tissue wet weight, pmol/(min*mg). Data were analyzed by one-way analysis of variance (one-way ANOVA) followed by Tukey’s post hoc test for comparisons between multiple groups. Results: Complex I respiration in C was compromised at ROSC 6hr compared to S (564.0±160.0 vs 2729.5±339.5, p<0.001). As expected, P and M restored complex I respiration (1224.4±328.6, p<0.001) and (1804.4±293.1, p<0.01) compared to C. P&M further consolidated Complex I respiration function recovery (2527.6±145.5). Conclusion: Combined Therapy with PEG-20k and MCC950 preserves post-resuscitation myocardial mitochondrial function in a rat model of CA and CPR.

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Abstract 14: Polyethylene Glycol-20k Improves Post-Resuscitation Cerebral Microcirculation in a Rat Model of Cardiac Arrest

Circulation ◽

10.1161/circ.138.suppl_2.14 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Qinyue Guo ◽

Jin Yang ◽

Zhangle Hu ◽

Yan Xiao ◽

Xiaobo Wu ◽

...

Keyword(s):

Polyethylene Glycol ◽

Rat Model ◽

Dry Weight ◽

Saline Group ◽

Dark Field ◽

Cell Swelling ◽

Cerebral Microcirculation ◽

Brain Swelling ◽

Cerebral Dysfunction ◽

Vascular Beds

Introduction: Polyethylene glycol-20k (PEG-20k) reduces severity of post CPR cerebral dysfunction, however the mechanism is yet unproven. In other vascular beds, PEG-20k osmotically reverses ischemia-induced metabolic cell swelling and decompresses the microcirculation, which improves flow and oxygen transfer. Hypothesis: We hypothesized that PEG-20k improves neurologic function by preserving microcirculatory blood flow and decreasing brain swelling. Methods: 32 S-D rats weighting between 450-550g were randomized into 4 groups: 1) Control (CPR+SALINE); 2) Treated (CPR+PEG-20k); 3) NO CPR+SALINE; 4) NO CPR+PEG-20k. CPR was initiated after 8 min of untreated ventricular fibrillation and continued for 8 min, then defibrillation was performed. PEG-20k was administered at the beginning of chest compression. Cerebral microcirculation was visualized at baseline, 2, 4 and 6 h after CPR by side-stream dark-field (SDF) imaging with a 5х imaging objective. Animals were euthanized with Euthasol (150 mg/kg) and brain swelling was assessed by comparing wet-to-dry weight ratios at 6h post resuscitation. Results: The wet to dry ratio in the CPR+SALINE group was significantly higher than the other three groups (p<0.05). PEG-20k attenuated the wet to dry ratio (p<0.05) compared with the CPR+SALINE group (Fig 1). A significant improvement of cerebral microcirculation was also observed in the CPR+PEG-20k group when compared with the CPR+SALINE group (Fig 2). Conclusions: PEG-20k given during resuscitation improves cerebral microcirculatory flow by increasing microcirculation and decreasing brain tissue swelling in a rat model of CA.

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A novel rat model of cardiopulmonary bypass (CPB) with cardiac arrest and precise hemodynamic assessment by conductance catheter technique

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-2007-967535 ◽

2007 ◽

Vol 55 (S 1) ◽

Author(s):

R Guenzinger ◽

SM Wildhirt ◽

H Schad ◽

W Heimisch ◽

N Mendler ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Bypass ◽

Rat Model ◽

Conductance Catheter ◽

Catheter Technique ◽

Hemodynamic Assessment

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Mild therapeutic hypothermia improves neurological outcomes in a rat model of cardiac arrest

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.05.014 ◽

2021 ◽

Author(s):

Liangliang Zhang ◽

Wei Liang ◽

Yiling Li ◽

Jie Yan ◽

Jingwen Xue ◽

...

Keyword(s):

Cardiac Arrest ◽

Therapeutic Hypothermia ◽

Rat Model ◽

Mild Therapeutic Hypothermia ◽

Neurological Outcomes

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A NEW CARDIAC ARREST RAT MODEL FOR BRAIN RESUSCITATION STUDIES

Critical Care Medicine ◽

10.1097/00003246-198103000-00414 ◽

1981 ◽

Vol 9 (3) ◽

pp. 247

Author(s):

Hans H. L. Hendrickx ◽

Sven Erik Gisvold ◽

Peter Safar ◽

Ken Swint ◽

John Mossy ◽

...

Keyword(s):

Cardiac Arrest ◽

Rat Model ◽

Brain Resuscitation

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Improved Early Postresuscitation EEG Activity for Animals Treated with Hypothermia Predicted 96 hr Neurological Outcome and Survival in a Rat Model of Cardiac Arrest

BioMed Research International ◽

10.1155/2013/312137 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Bihua Chen ◽

Feng-Qing Song ◽

Lei-Lei Sun ◽

Ling-Yan Lei ◽

Wei-Ni Gan ◽

...

Keyword(s):

Cardiac Arrest ◽

Rat Model ◽

Neurological Outcome ◽

Cardiac Pacing ◽

Aortic Pressure ◽

Sprague Dawley ◽

Burst Frequency ◽

Eeg Activity ◽

Favorable Neurological Outcome ◽

Hypothermic Group

Purpose.To investigate the effect of hypothermia on 96 hr neurological outcome and survival by quantitatively characterizing early postresuscitation EEG in a rat model of cardiac arrest.Materials and Methods.In twenty male Sprague-Dawley rats, cardiac arrest was induced through high frequency transesophageal cardiac pacing. Cardiopulmonary resuscitation was initiated after 5 mins untreated arrest. Immediately after resuscitation, animals were randomized to either 2 hrs of hypothermia (N=10) or normothermia (N=10). EEG, ECG, aortic pressure, and core temperature were continuously recorded for 6 hrs. Neurological outcome was evaluated daily during the 96 hrs postresuscitation period.Results.No differences in the baseline measurements and resuscitation outcome were observed between groups. However, 96 hr neurological deficit score (204 ± 255 versus 500 ± 0,P=0.005) and survival (6/10 versus 0/10,P=0.011) were significantly better in the hypothermic group. Quantitative analysis of early postresuscitation EEG revealed that burst frequency and spectrum entropy were greatly improved in the hypothermic group and correlated with 96 hr neurological outcome and survival.Conclusion.The improved burst frequency during burst suppression period and preserved spectrum entropy after restoration of continuous background EEG activity for animals treated with hypothermia predicted favorable neurological outcome and survival in this rat model of cardiac arrest.

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