Abstract 107: Mitochondrial Dysfunction Mediated Myocardial Stunning Following Resuscitation From Cardiac Arrest

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Willard W Sharp ◽  
Lin Piao ◽  
Yong Fang ◽  
David G Beiser ◽  
James K Liao ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Myocardial Stunning ◽  
Mitochondrial Dynamics ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Spontaneous Circulation ◽  
Contractile Dysfunction ◽  
Myocardial Contractile ◽  
Induced Changes

Rationale: Severe myocardial contractile dysfunction following resuscitation from cardiac arrest (CA) is a major contributor to CA mortality. The pathophysiology and etiology of this dysfunction is not known and there are no pharmacological therapies known to improve outcomes. Previously, we demonstrated that Dynamin related protein 1 (Drp1) is activated and recruited to the mitochondria during CA and that the Drp1 inhibitor Mdivi-1 improves post CA survival. Objective: To determine the effects of CA length on myocardial and mitochondrial function. We also sought to determine the effects of Mdivi-1 on post CA outcomes. Methods and Results: Asystolic cardiac arrest (CA) was induced in mice by IV injection of 0.08 mg/g KCL. CPR begun at 4, 8, 12, and 16 minutes post-cardiac arrest had rates of return of spontaneous circulation (ROSC) of 100%(12/12), 93%(14/15), 71%(10/14), and 44% (4/9) and 2-hour survival of 100%(12/12), 67%(10/15), 50%(7/14), and 11%(1/9). Transthoracic echocardiography 15 min post-resuscitation demonstrated percent fractional shortening of 36±4% (Sham,n=6), 30±4% (4 minCA,n=11), 24±5% (8minCA,n=10), 15±2% (12minCA,n=12). In surviving animals, myocardial dysfunction persisted for 2 hours post-resuscitation, but slowly recovered to baseline by 72 hours. No evidence of myocardial necrosis, inflammation, or apoptosis was noted following resuscitation. Progressive increases in mitochondrial derived reactive oxygen species (ROS) during CA was observed by MitoSOX red myocardial tissue staining. Mitochondria isolated from 12 min CA hearts demonstrated decreased substrate coupled and uncoupled respiration. Mdivi-1, a mitochondrial inhibitor of division (fission), improved survival and neurological scores in mice following an 8 min cardiac arrest compared to controls. Conclusions: Severe, time dependent myocardial stunning (contractile dysfunction in the absence of irreversible injury) was observed following asystolic cardiac arrest. This myocardial stunning was associated with mitochondrial injury and improved by an inhibitor of Drp1. Strategies targeting ischemia/reperfusion-induced changes in mitochondrial dynamics hold promise for improving myocardial function and survival following cardiac arrest.

Abstract P15: Periodic Acceleration (pGz) Preconditioning in Swine Increases Endothelial Derived NO and Phosphorylated eNOS via Akt Pathway

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jose A Adams ◽  
Jaqueline Arias ◽  
Jorge Bassuk ◽  
Heng Wu ◽  
Arkady Uryash ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Spontaneous Circulation ◽  
Akt Pathway ◽  
Phosphorylated Akt ◽  
Manual Chest Compression ◽  
Periodic Acceleration ◽  
Pulsatile Shear Stress

Periodic acceleration (pGz) is the motion of the supine body using a motorized platform (3Hz & ±0.4G). pGz produces pulsatile shear stress increasing release of endothelial derived NO (eNO) which, also decreases myocardial stunning and improves outcomes from ventricular fibrillation (VF) cardiac arrest. Preconditioning with pGz (PRE-pGz) prior to VF cardiac arrest ameliorates global post resuscitation cardiac dysfunction and reduces arrhythmias. To test whether pGz and PRE-pGz increase eNOS and phosphorylated eNOS (p-eNOS) via the PI3-kinase-Akt pathway, anesthetized, intubated male swine (40 –50lbs) were studied. Five animals had no intervention (BL) and 5 received 1 hr pGz preconditioning (pGz) followed by Western Blot of myocardial tissue. Additional animals (10 per group) received 1 hr pGz (PRE-pGz) or no treatment (CPR-CONT). In the latter groups VF was electrically induced and unsupported for 8 min followed by continuous manual chest compression and defibrillation for 10 min or until return of spontaneous circulation (ROSC). PRE-pGz animals showed less hemodynamically significant arrhythmias after ROSC than CPR-CONT (35 vs 7; p<0.05) and less myocardial stunning. eNOS and phosphorylated-eNOS (p-eNOS) significantly increased after pGz and after CPR but were significantly higher in pGz preconditioned animals along with increased phosphorylated Akt (p-Akt). The graph below shows % changes relative to BL (M±SD). *p < 0.01 PRE-pGz vs CPR-CONT. Conclusion: pGz applied prior to ischemia reperfusion injury increases eNOS and p-eNOS expression and increased p-Akt. Thus, pGz preconditioning protects myocardium during I-R in part by activating eNOS through p-Akt

scholarly journals Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1-Mediated Mitochondrial Fission after Cardiac Arrest-Induced Myocardial Damage

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jun Wu ◽  
Hui Chen ◽  
Jiahong Qin ◽  
Nan Chen ◽  
Shiqi Lu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Mitochondrial Dysfunction ◽  
Myocardial Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Specific Inhibitor ◽  
Myocardial Damage ◽  
Spontaneous Circulation ◽  
Flavonoid Compound

Myocardial injury after cardiac arrest (CA) often results in severe myocardial dysfunction and death involving mitochondrial dysfunction. Here, we sought to investigate whether baicalin, a natural flavonoid compound, exerts cardioprotection against CA-induced injury via regulating mitochondrial dysfunction. We subjected the rats to asphyxia CA after a daily baicalin treatment for 4 weeks. After the return of spontaneous circulation, baicalin treatment significantly improved cardiac function performance, elevated survival rate from 35% to 75%, prevented necrosis and apoptosis in the myocardium, which was accompanied by reduced phosphorylation of Drp1 at serine 616, inhibited Drp1 translocation to the mitochondria and mitochondrial fission, and improved mitochondrial function. In H9c2 cells subjected to simulated ischemia/reperfusion, increased phosphorylation of Drp1 at serine 616 and subsequently enhanced mitochondrial Drp1 translocation as well as mitochondrial fission, augmented cardiomyocyte death, increased reactive oxygen species production, released cytochrome c from mitochondria and injured mitochondrial respiration were efficiently improved by baicalin and Drp1 specific inhibitor with Mdivi-1. Furthermore, overexpression of Drp1 augmented excessive mitochondrial fission and abolished baicalin-afforded cardioprotection, indicating that the protective impacts of baicalin are linked to the inhibition of Drp1. Altogether, our findings disclose for the first time that baicalin offers cardioprotection against ischemic myocardial injury after CA by inhibiting Drp1-mediated mitochondrial fission. Baicalin might be a prospective therapy for the treatment of post-CA myocardial injury.

Abstract 211: UAMC-3203 Reduces the Severity of Post-resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Tao Jin ◽  
Cheng Cheng ◽  
Hui Li ◽  
Lian Liang ◽  
Guozhen Zhang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Cardiac Function ◽  
Rat Model ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Spontaneous Circulation ◽  
Sprague Dawley

Introduction: Previous studies have demonstrated that ferroptosis, a newly defined iron-dependent cell death, mediates ischemia/reperfusion induced cardiomyopathy. However, it is unclear whether ferroptosis plays a role in post-resuscitation myocardial dysfunction (PRMD). This study investigated the effects of UAMC-3203, a novel analog of ferroptosis specific inhibitors, on myocardial function after cardiopulmonary resuscitation (CPR). Hypothesis: Administration of UAMC-3203 during CPR alleviates PRMD in a rat model of cardiac arrest (CA) and CPR. Methods: 18 male Sprague-Dawley rats weighing between 450-550g were randomized into 3 groups: 1) Sham, 2) Control, and 3) UAMC-3203 (5mg/kg, IP at start of precordial compression). Ventricular fibrillation (VF) was induced and continued for 6min. CPR was then initiated for 8min, after which defibrillation was attempted. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured by echocardiography at baseline, 15min, 1h, 3h and 6h respectively after return of spontaneous circulation (ROSC). Results: A significant reduction in cardiac function was observed after resuscitation. At 15 minutes after ROSC, ultrasound showed no difference in cardiac function between UAMC and control. However, at 1, 3, and 6 h after ROSC, UAMC significantly improved myocardial function (p<0.05) (Fig. 1). Conclusion: A ferroptosis-specific inhibitor, UAMC-3203, alleviated PRMD significantly in a rat of model of CA and CPR. Further study is needed to determine the benefit of this agent in larger animals and potential safety in humans before it can be tested in clinical resuscitation.

Abstract 104: N-Acetyl Cysteine Improves Post Reperfusion Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Return of Spontaneous Circulation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Fenglian He
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Spontaneous Circulation ◽  
Control Group ◽  
Successful Resuscitation ◽  
Return Of Spontaneous Circulation

N-acetylcysteine improves post reperfusion myocardial dysfunction in a Rat Model of Cardiac Arrest and return of spontaneous circulation Introduction: Studies have demonstrated that N-acetylcysteine (NAC) can attenuate regional myocardial ischemia/reperfusion injury and improved myocardial dysfunction. However, it is not clear whether NAC could protect post reperfusion myocardial dysfunction (PRMD) after cardiac arrest (CA) and return of spontaneous circulation (ROSC). In this study, we investigated the effect of NAC on post reperfusion myocardial dysfunction in a rat model of CA and ROSC. Hypothesis: NAC reduces the severity of PRMD in a rat model of CA and ROSC. Method: Ten healthy male Sprague-Dawley rats weighting 450g–550g were utilized, and randomly divided into two groups: 1) control group; 2) NAC group (150mg/kg). Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins, and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline, 2, 4 and 6 hours after successful resuscitation. Result: Except one in the control group, all animals were resuscitated. Myocardial function of post-resuscitation was significantly decreased in all animals. However, myocardial function gradually improved in animals treated with NAC when compared with those in control groups (Figure). Conclusion: In a rat model of cardiac arrest, NAC improves post-resuscitation myocardial dysfunction Figure The post-resuscitation myocardial dysfunction. BL, baseline; VF, ventricular fibrillation; CO, cardiac output; EF, ejection fraction; MPI, myocardial performance index; CPR, cardiopulmonary resuscitation; C group,control group; N group, NAC intervention group; * p < 0.05.vs. the C group.

Abstract 148: Zoniporide Combined with α-Methylnorepinephrine Appears Highly Effective for Resuscitation from Cardiac Arrest in a Rat Model of Ventricular Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lorissa Lamoureux ◽  
Herbert K Whitehouse ◽  
Jeejabai Radhakrishnan ◽  
Raúl J Gazmuri
Keyword(s):  
Cardiac Arrest ◽  
Chest Compression ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Survival Times ◽  
Highly Effective ◽  
Electrical Shocks ◽  
Novel Strategy

Background: We have reported in rat and swine models of cardiac arrest that sodium hydrogen exchanger isoform-1 (NHE-1) inhibition facilitates resuscitation, ameliorates myocardial dysfunction, and improves survival. Others have reported that α-methylnorepinephrine (α-MNE) - a selective α2-adrenoreceptor agonist - is superior to epinephrine given its lack of β-agonist effects. We examined in a rat model of VF and closed-chest resuscitation the effects of combining the NHE-1 inhibitor zoniporide (ZNP) with α-MNE. Methods: VF was electrically induced in 32 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes after which resuscitation was attempted by an 8 minute interval of chest compression and delivery of electrical shocks. Rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before starting chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest-compressions establishing 4 groups of 8 rats each. Successfully resuscitated rats were monitored for 240 minutes. Results: The number of rats that had return of spontaneous circulation and then survived 240 min were: α-MNE(-)/ZNP(-) 4 and 2; α-MNE(-)/ZNP(+) 5 and 5; α-MNE(+)/ZNP(-) 2 and 1; and α-MNE(+)/ZNP(+) 7 and 7 yielding a statistically significant effect on overall survival times corresponding to 105 ± 114, 150 ± 124, 58 ± 108, and 210 ± 85 min, respectively (p < 0.045). Post-resuscitation lactate levels were attenuated in all treatment groups with the greatest effect by the α-MNE(+)/ZNP(+) combination without major differences in hemodynamic function (Table). Conclusion: We confirm a beneficial effect resulting from the combination of ZNP (given to attenuate myocardial reperfusion injury) and α-MNE (given to augment peripheral vascular resistance during chest compression without the detrimental actions of epinephrine). The proposed combination may prove to be a highly effective novel strategy for resuscitation from cardiac arrest.

Abstract 10773: Curcumin Improves the Outcomes of Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhengfei Yang ◽  
Jiangang Wang ◽  
Lu Yin ◽  
Shen Zhao ◽  
Ziren Tang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Placebo Group ◽  
Rat Model ◽  
Myocardial Function ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Sprague Dawley ◽  
Successful Resuscitation ◽  
Pre Treatment

Introduction: Curcumin has been proven to provide potent protection of vital organs against regional ischemia reperfusion injury. In this study, we investigated the effects of curcumin on the outcomes of CPR in a rat model of cardiac arrest. Hypothesis: Curcumin reduces the severity of post-CPR myocardial dysfunction and prolong the duration of survival. Method: Sixteen male Sprague-Dawley rats weighing between 450-550g were randomized into two groups: 1) Placebo; 2) Curcumin (100 mg/kg) pre-treatment. Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation. The duration of survival was observed for total 72 hours. Result: Six animals in the placebo group and seven in the curcumin group were successfully resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. However, myocardial function gradually improved 4 hours after resuscitation and was significantly better in the animals pre-treated with curcumin (Figure). Significantly shorter duration of survival of 40±29 hours was observed in the placebo group. Conclusion: In a rat model of cardiac arrest, curcuminim proves post-resuscitation myocardial dysfunction and prolongs the duration of survival.

Post–Cardiac Arrest Syndrome

2020 ◽  
Vol 31 (4) ◽  
pp. 383-393
Author(s):  
Linda Dalessio
Keyword(s):  
Cardiac Arrest ◽  
Myocardial Dysfunction ◽  
The United States ◽  
Spontaneous Circulation ◽  
Clinical State ◽  
Precipitating Factors ◽  
Patient Health ◽  
Global Brain ◽  
The Brain ◽  
Post Cardiac Arrest Syndrome

More than 356 000 out-of-hospital cardiac arrests occur in the United States annually. Complications involving post–cardiac arrest syndrome occur because of ischemic-reperfusion injury to the brain, lungs, heart, and kidneys. Post–cardiac arrest syndrome is a clinical state that involves global brain injury, myocardial dysfunction, macrocirculatory dysfunction, increased vulnerability to infection, and persistent precipitating pathology (ie, the cause of the arrest). The severity of outcomes varies and depends on precipitating factors, patient health before cardiac arrest, duration of time to return of spontaneous circulation, and underlying comorbidities. In this article, the pathophysiology and treatment of post–cardiac arrest syndrome are reviewed and potential novel therapies are described.

scholarly journals Elevated Plasma Soluble PD-L1 Levels in Out-of-Hospital Cardiac Arrest Patients

2021 ◽  
Vol 10 (18) ◽  
pp. 4188
Author(s):  
Miho Sumiyoshi ◽  
Eiji Kawamoto ◽  
Yuki Nakamori ◽  
Ryo Esumi ◽  
Kaoru Ikejiri ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ischemia Reperfusion ◽  
Plasma Concentrations ◽  
Spontaneous Circulation ◽  
University Hospital ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immune Functions ◽  
Protein Levels ◽  
Hospital Cardiac Arrest

Background: A deregulated immune system has been implicated in the pathogenesis of post-cardiac arrest syndrome (PCAS). A soluble form of programmed cell death-1 (PD-1) ligand (sPD-L1) has been found at increased levels in cancer and sustained inflammation, thereby deregulating immune functions. Here, we aim to study the possible involvement of sPD-L1 in PCAS. Methods: Thirty out-of-hospital cardiac arrest (OHCA) patients consecutively admitted to the ER of Mie University Hospital were prospectively enrolled. Plasma concentrations of sPD-L1 were measured by an enzyme-linked immunosorbent assay in blood samples of all 30 OHCA patients obtained during cardiopulmonary resuscitation (CPR). In 13 patients who achieved return-of-spontaneous-circulation (ROSC), sPD-L1 levels were also measured daily in the ICU. Results: The plasma concentrations of sPD-L1 in OHCA were significantly increased; in fact, to levels as high as those observed in sepsis. sPD-L1 levels during CPR correlated with reduced peripheral lymphocyte counts and increased C-reactive protein levels. Of 13 ROSC patients, 7 cases survived in the ICU for more than 4 days. A longitudinal analysis of sPD-L1 levels in the 7 ROSC cases revealed that sPD-L1 levels occurred in parallel with organ failure. Conclusions: This study suggests that ischemia- reperfusion during CPR may aberrantly activate immune and endothelial cells to release sPD-L1 into circulation, which may play a role in the pathogenesis of immune exhaustion and organ failures associated with PCAS.

scholarly journals Pediatric Cardiac Arrest

2020 ◽  
Author(s):  
Priscilla Yu ◽  
Ivie D. Esangbedo ◽  
Lakshmi Raman ◽  
Cindy Darnell Bowens
Keyword(s):  
Cardiac Arrest ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Temperature Management ◽  
Patient Centered ◽  
Recent Developments ◽  
Cpr Quality ◽  
Current Guidelines

This chapter will focus on four important topics in pediatric cardiac arrest. We will highlight recent developments in pediatric CPR quality, medications used in cardiac arrest, ECPR, and post-cardiac arrest care (PCAC) and discuss the existing literature behind AHA guidelines and gaps in knowledge. Optimization of CPR quality is critical during cardiac arrest. We will summarize literature regarding current guidelines which target provider-centered goals and discuss evidence behind patient-centered goals. We will also discuss the evidence behind drugs used in the PALS guidelines. In cases of refractory cardiac arrest, ECMO can be lifesaving; however, there are still many gaps in our knowledge of this field. We will summarize the literature regarding determination of candidacy, cannulation strategies, resuscitation practices during ECPR, and outcomes. After a cardiac arrest, PCAC is crucial to minimize further injury from post-cardiac arrest syndrome (PCAS). The main goals of PCAC are to prevent further brain injury, treat myocardial dysfunction, and systemic ischemia/reperfusion injury. We will discuss AHA guidelines on oxygenation and ventilation goals, targeted temperature management, hemodynamic monitoring, and neuromonitoring.

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