scholarly journals Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jun Jiang ◽  
Xiangshao Fang ◽  
Yue Fu ◽  
Wen Xu ◽  
Longyuan Jiang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Cardiopulmonary Resuscitation ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Rat Model ◽  
Mitochondrial Function ◽  
High Energy ◽  
Mitochondrial Morphology ◽  
High Energy Phosphates

Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA). Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF). We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

Abstract 289: Relationship Between Myocardial Glycogen Concentrations and Amplitude Spectrum Area During Ventricular Fibrillation in a Rat Model of Cardiac Arrest and Resuscitation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Qiaohua Hu ◽  
Xiangshao Fang ◽  
Zhengfei Yang ◽  
Wanchun Tang
Keyword(s):  
Cardiac Arrest ◽  
Energy Metabolism ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Glycogen Content ◽  
Amplitude Spectrum ◽  
High Energy ◽  
Myocardial Energy Metabolism ◽  
Spectrum Area ◽  
The Relationship

Introduction: Myocardial high-energy phosphate (ATP) levels has been demonstrated correlating with amplitude spectrum area (AMSA) during ventricular fibrillation (VF) in previous experimental studies. In the present study, we investigated the relationship between AMSA and myocardial glycogen content (MGC),which can be used to reflect the status of myocardial energy metabolism indirectly during VF. Hypothesis: AMSA has a significantly correlation with MGC during VF in a rat model of cardiac arrest and resuscitation. Methods: Twenty male Sprague-Dawley rats weighing 350 to 450 g were utilized and randomized into two groups: VF and cardiopulmonary resuscitation (CPR) (VF/CPR group) or untreated VF (VF group). 5 mins of CPR was performed after 10 mins of untreated VF in VF/CPR animals. Amplitude spectrum area (AMSA) at VF 5, 10 and 15 mins were calculated from ECG signals. The rats’ hearts were quickly removed at the predetermined time of 15 min for determines the glycogen contents by the anthrone reagent method using a glycogen assay kit. Results: AMSA values significantly decreased during untreated VF in both VF and VF/CPR animals. However, much greater AMSA during CPR was achieved by the VF/CPR group in comparison with the VF group. There was a marked and negative relationship between AMSA at VF 15 min and MGC. (Figure). Conclusion: MGC was significantly and negatively correlated with AMSA during VF in this rat model of cardiac arrest and resuscitation. In clinical practice, we can use AMSA to reflect the state of myocardial energy metabolism indirectly. Figure The changes of AMSA and relationship between AMSA and glycogen content:(A) The change of AMSA between VF/CRP group and VF group;(B) The relationship between AMSA and glycogen content. AMSA, amplitude spectrum area; V, time of ventricular fibrillation; # p <0.05 vs. V4.

Abstract 142: Combined Therapy with Polyethylene Glycol-20k and MCC950 Preserves Post-resuscitation Myocardial Mitochondrial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Lian Liang ◽  
Guozhen Zhang ◽  
Hui Li ◽  
Cheng Cheng ◽  
Tao Jin ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Polyethylene Glycol ◽  
Cardiopulmonary Resuscitation ◽  
Rat Model ◽  
Mitochondrial Function ◽  
Complex I ◽  
Myocardial Dysfunction ◽  
Combined Therapy ◽  
Chain Complex ◽  
Sprague Dawley

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.

Cardiopulmonary resuscitation ameliorates myocardial mitochondrial dysfunction in a cardiac arrest rat model

2020 ◽  
Vol 38 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Wen Xu ◽  
Yue Fu ◽  
Longyuan Jiang ◽  
Zhengfei Yang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Mitochondrial Dysfunction ◽  
Rat Model

Abstract 16641: The SGLT2 Inhibitor Ertugliflozin Induces Oxidative Phosphorylation Gene Expression and Improves Systolic Function Independent of Diabetes in Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dominique Croteau ◽  
Ivan Luptak ◽  
Fuzhong Qin ◽  
Jordan M Chambers ◽  
Ion A Hobai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Function ◽  
Systolic Function ◽  
High Energy ◽  
Enrichment Score ◽  
High Energy Phosphates ◽  
Gene Set ◽  
Work Demand ◽  
Myocardial Gene Expression

Background: Inhibitors of sodium glucose linked transporter 2 (SGLT2i) improve heart failure (HF) outcomes in patients independent of diabetes. While animal studies suggest SGLT2i improve cardiac metabolism, the effect of SGLT2i on mitochondrial function in the heart is not known. Our goal was to assess the effects of SGLT2i on mitochondrial function, high energy phosphates and genes encoding mitochondrial proteins in hearts of mice with and without diet-induced diabetes. Methods & Results: Ertugliflozin (Ertu; 0.5 mg/g) was given for 4 months to mice fed a high fat, high sucrose (HFHS) diet that causes diabetic cardiomyopathy or control diet (CD). Mitochondrial function was measured in isolated cardiac mitochondria. Myocardial energetics were assessed by NMR spectroscopy simultaneously with systolic function in isolated beating hearts. Myocardial gene expression was assessed by RNA seq using gene set analysis. HFHS diet caused myocardial hypertrophy and diastolic dysfunction, mitochondrial dysfunction (decreased ATP production, increased reactive oxygen species release) and an impaired energetic response to increased work demand - all of which were prevented by Ertu. Systolic function, as reflected by the rate x pressure product (RPP), was super-normalized to a value 124% of CD hearts at high work demand. In control mice, Ertu had no effect on isolated mitochondria function or high energy phosphates, but similar to HFHS hearts, caused super-normalization of RPP to 125% of CD hearts. Myocardial gene expression analysis revealed oxidative phosphorylation (OXPHOS) as the top scoring gene set that was both down-regulated by HFHS with a normalized enrichment score (NES) of -2.08, and up-regulated by Ertu in HFHS (NES, +3.32 vs HFHS). OXPHOS was the top scoring gene set up-regulated by Ertu a) across all groups while controlling for diet (NES, +3.71) and b) in CD-fed mice only (NES, +3.34). Conclusion: The super-normalization of systolic function and induction of the OXPHOS gene set by Ertu is independent of diabetic status. Pro-metabolic remodeling of the myocardium by Ertu may support increased systolic function and contribute to the beneficial actions of Ertu in states such as HF that are associated with impaired cardiac mitochondrial function.

Alterations in the distribution of high-energy phosphates during ischemia in a canine model of reperfusion-induced ventricular fibrillation

1985 ◽  
Vol 110 (3) ◽  
pp. 590-594 ◽  
Author(s):  
Sharon L. Hale ◽  
Kevin J. Alker ◽  
Huey-Ming Lo ◽  
Joanne S. Ingwall ◽  
Robert A. Kloner
Keyword(s):  
Ventricular Fibrillation ◽  
Canine Model ◽  
High Energy ◽  
High Energy Phosphates

scholarly journals Melatonin improves neurological outcomes and preserves hippocampal mitochondrial function in a rat model of cardiac arrest

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207098 ◽  
Author(s):  
Linghui Yang ◽  
Jing Wang ◽  
Yan Deng ◽  
Cansheng Gong ◽  
Qin Li ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Rat Model ◽  
Mitochondrial Function ◽  
Neurological Outcomes

scholarly journals Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

2020 ◽  
Vol 11 ◽  
Author(s):  
Hao-Jie Ma ◽  
Cong Gai ◽  
Yuan Chai ◽  
Wan-Di Feng ◽  
Cui-Cui Cheng ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mitochondrial Dysfunction ◽  
Cell Survival ◽  
Mitochondrial Function ◽  
Survival Rates ◽  
Transient Transfection ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Protein Levels ◽  
Atp Levels

As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson’s disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.

P490Time boundaries of three-phase time-sensitive model for ventricular fibrillation cardiac arrest

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
Y Goto ◽  
A Funada ◽  
T Maeda ◽  
F Okada ◽  
Y Goto
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Cardiopulmonary Resuscitation ◽  
Emergency Medical Services ◽  
Medical Services ◽  
Phase Time ◽  
Emergency Medical ◽  
Three Phase ◽  
Emergency Medical Services Personnel ◽  
Neurologically Intact

Abstract Funding Acknowledgements Japan Society for the Promotion of Science (KAKENHI Grant No. 18K09999) Background Recent clinical evidence has suggested that the pathophysiology of ventricular fibrillation (VF) cardiac arrest may consist of three time-sensitive phases, namely electrical, circulatory, and metabolic. According to this model of cardiopulmonary resuscitation (CPR), the optimal treatment of cardiac arrest is phase-specific. The potential survival benefit of bystander cardiopulmonary resuscitation (BCPR) depends in part on ischemic time (i.e., the collapse-to-shock interval), with the greatest benefit occurring during the circulatory (second) phase. However, the time boundaries between phases are not precisely defined in the current literature. Purpose The purpose of the present study was to determine the time boundaries of the three-phase time-sensitive model for VF cardiac arrest. Methods We reviewed 20,741 adult patients with initial VF after witnessed out-of-hospital cardiac arrest from a presumed cardiac origin who were included in the All-Japan Utstein-style registry from 2013 to 2017. We excluded patients who underwent bystander defibrillation prior to arrival of emergency medical services personnel. The study end point was 1-month neurologically intact survival (Cerebral Performance Category scale 1 or 2). Collapse-to-shock interval was defined as the time from collapse to first shock delivery by emergency medical services personnel. Patients were divided into two groups, BCPR (n = 11,606, 56.0%) and non-BCPR (n = 9135, 44.0%), according to whether they had received BCPR or not. Results The rate of 1-month neurologically intact survival in the BCPR group was significantly higher than that in the non-BCPR group (27.9% [3237/11,606] vs 17.9% [1632/9135], P &lt; 0.0001; adjusted odds ratio [OR], 1.90; 95% confidence interval [CI], 1.75–2.07; P &lt; 0.0001). Overall, increased collapse-to-shock interval was associated with significantly decreased adjusted odds of 1-month neurologically intact survival (adjusted OR for each 1-minute increase, 0.94; 95% CI, 0.93–0.95; P &lt; 0.0001). In the BCPR group, the ranges of collapse-to-shock interval that were associated with increased adjusted 1-month neurologically intact survival were from 7 minutes (adjusted OR, 1.95; 95% CI, 1.44–2.63; P &lt; 0.0001) to 17 minutes (adjusted OR, 2.82; 95% CI, 1.62–4.91; P = 0.0002) as compared with those in the non-BCPR group. However, the increase in neurologically intact survival of the BCPR group became statistically insignificant as compared with that of the non-BCPR group when the collapse-to-shock interval was outside these ranges. Conclusions The above-mentioned findings suggest that the time boundaries of the three-phase time-sensitive model for VF cardiac arrest may be as follows: electrical phase, from collapse to &lt;7 minutes; circulatory phase, from 7 to 17 minutes; and metabolic phase, &gt;17 minutes onward from collapse.

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