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.

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 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.

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.

scholarly journals Combined Therapy With Polyethylene Glycol‐20k and MCC950 Preserves Post‐Resuscitated Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Lian Liang ◽  
Guozhen Zhang ◽  
Hui Li ◽  
Cheng Cheng ◽  
Tao Jin ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Polyethylene Glycol ◽  
Cardiopulmonary Resuscitation ◽  
Cardiac Troponin ◽  
Myocardial Function ◽  
Troponin I ◽  
Combined Therapy ◽  
Spontaneous Circulation ◽  
Sublingual Microcirculation ◽  
Nlrp3 Inflammasomes

Background To investigate the therapeutic potential of combined therapy with polyethylene glycol‐20k (PEG‐20k) and MCC950 on post‐resuscitation myocardial function in a rat model of cardiac arrest. Methods and Results Thirty rats were randomized into 5 groups: Sham, Control, PEG‐20k, MCC950, PEG‐20k+ MCC950. Except for sham, animals were subjected to 6 minutes of ventricular fibrillation followed by 8 minutes cardiopulmonary resuscitation. Two milliliters PEG‐20k was administered by intravenous injection coincident with the start of cardiopulmonary resuscitation; MCC950 (10 mg/kg), a highly selective NLRP3 inflammasome inhibitor, was delivered immediately after restoration of spontaneous circulation. Myocardial function, sublingual microcirculation, mitochondrial function, plasma cardiac troponin I, and interleukin‐1β, expression of proteins in SIRT1 (sirtuin 1)/PGC‐1α (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha) and NLRP3 (the NOD‐like receptor family protein 3) inflammasome pathways were evaluated. Following cardiopulmonary resuscitation, myocardial function was compromised with a significantly decreased cardiac output, ejection fraction, and increased myocardial performance index, cardiac troponin I. Sublingual microcirculation was disturbed with impaired perfused vessel density and microvascular flow index. Cardiac arrest reduced mitochondrial routine respiration, Complex I‐linked respiration, respiratory control rates and oxidative phosphorylation coupling efficiency. PEG‐20k or MCC950 alone restored mitochondrial respiratory function, restituted sublingual microcirculation, and preserved myocardial function, whereas a combination of PEG‐20k and MCC950 further improved these aspects. PEG‐20k restored the expression of SIRT1 and PGC‐1α, and blunted activation of NLRP3 inflammasomes. MCC950 suppressed expression of cleaved‐caspase‐1/pro‐caspase‐1, ASC (apoptosis‐associated speck‐like protein), GSDMD [gasdermin d], and interleukin‐1β. Conclusions Combined therapy with PEG‐20k and MCC950 is superior to either therapy alone for preserving post‐resuscitated myocardial function, restituting sublingual microcirculation at restoration of spontaneous circulation at 6 hours. The responsible mechanisms involve upregulated expression of SIRT1/PGC1‐α in tandem with inhibition of NLRP3 inflammasomes.

Abstract P34: Nitrite Therapy upon Resuscitation from Cardiac Arrest Reversibly Inhibits Mitochondrial Complex I Reducing ROS Burst and Improving Cardiac Function and Survival

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Cameron Dezfulian ◽  
Sruti Shiva ◽  
Akshay Pendyal ◽  
Aleksey Alekseyenko ◽  
Stasia A Anderson ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Complex I ◽  
Myocardial Dysfunction ◽  
Cardiac Contractility ◽  
Respiratory Control ◽  
Chain Complex ◽  
Ros Generation ◽  
Atp Production ◽  
Amplex Red ◽  
Ros Burst

Nitrite reversibly S-nitrosates mitochondrial electron transport chain complex I (cxI) resulting in transient inhibition and reduction of pathological ROS burst after ischemia. We hypothesized that nitrite therapy at CPR initiation could thus improve cardiac contractility and mortality. Anesthetized C57BL/6 mice underwent hyperkalemic cardiac arrest maintained for 12min at 36.5C prior to randomly receiving blinded IV nitrite or saline placebo, epinephrine, chest compressions and ventilation for up to 150 sec. ROSC was obtained in excess of 90% in both groups. Hearts were excised just prior to asystole, 5 or 60 minutes after the initiation of CPR and mitochondria isolated. Respiration was assessed by oxygen consumption after providing the cxI substrate pyruvate or the complex II (cxII) substrate succinate. CxI activity was directly assayed by NADH oxidation, peroxide generation measured by Amplex Red peroxidation and ATP production quantified by luciferin luminescence. Nitrite therapy was associated with improved hemodynamics and significantly improved LVEF and RVEF (Table 1 ) and better 22h survival (HR 2.72 [95% CI:1.1– 6.7]). Nitrite significantly reduced cxI mediated respiration 5 min post-CPR with loss of inhibition by 60min based on respiration and ATP production (Table II ). Respiration efficiency (respiratory control ratio) did not change, nor was there significant cxII inhibition. Early cxI inhibition was associated with significantly less ROS. Nitrite therapy transiently and reversibly inhibits cxI reducing reperfusion ROS-mediated injury and resulting in less myocardial dysfunction and death after cardiac arrest. Myocardial dysfunction occurs after cardiac arrest and is reduced with nitrite therapy Nitrite therapy specifically and reversibly inhibits complex I and reduces ROS generation

Abstract 140: Effects of ω-3 Polyunsaturated Fatty Acids on Systemic Inflammation and Post-resuscitation Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Cheng Cheng ◽  
Hui Li ◽  
Tao Jin ◽  
Lian Liang ◽  
Guozhen Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cardiac Arrest ◽  
Polyunsaturated Fatty Acids ◽  
Systemic Inflammation ◽  
Rat Model ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Tnf Α

Introduction: Massive systemic inflammation is a primary cause of myocardial dysfunction following cardiac arrest (CA) and resuscitation (CPR). We investigated the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFA) on systemic inflammation and myocardial function after CA and CPR. Hypothesis: Administration of ω-3 PUFA at the start of CPR will alleviate post CPR inflammation and improve cardiac function in a rat model of CA and CPR. Methods: 18 male Sprague-Dawley rats weighing between 450g-550g were randomized into three groups: Sham, Control, and ω-3 PUFA. Ventricular fibrillation (VF) was induced and untreated for 6 min. 4J defibrillation was attempted after 8 min of CPR. Saline placebo or ω-3 PUFA (5mL/kg) was infused at the start of CPR and continued for 4h. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured by echocardiography at baseline, 1, 3 and 6h after return of spontaneous circulation (ROSC). Inflammatory cytokines (IL-6 and TNF-α) and cardiac biomarker (cTnI) levels in plasma were detected at baseline and 6 hrs after ROSC. Results: A decrease in EF and CO and an increase in MPI occurred after resuscitation. Significant improvement was noted in ω-3 PUFA compared to control animals (p<0.05) (Fig. 1). ELISA analysis showed increased plasma IL-6, TNF-α, and cTnI in post-resuscitated rats. Administration of ω-3 PUFA attenuated the rise in these plasma biomarkers (p<0.05) (Fig. 2). Conclusion: Administration of ω-3 PUFA attenuates post-resuscitation systemic inflammation and improves myocardial function in a rat model of CA and CPR.

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia

2006 ◽  
Vol 101 (4) ◽  
pp. 1091-1096 ◽  
Author(s):  
Xiangshao Fang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Lei Huang ◽  
Yun-Te Chang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Coronary Artery ◽  
Cardiopulmonary Resuscitation ◽  
Myocardial Ischemia ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Chronic Myocardial Ischemia

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.

Abstract 11029: Netrin-1 Alleviates Post-Resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lu Yin ◽  
Shen Zhao ◽  
JoongBum Moon ◽  
Peng Sun ◽  
Jiangang Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Saline Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group 2

Introduction: Post-resuscitation myocardial dysfunction has been recognized as one of the major causes of fatal outcomes after initial successful cardiopulmonary resuscitation (CPR). Previous research demonstrated that Netrin-1 improved post ischemic injury cardiac function via preservation of mitochondrial integrity. In the present study, we investigated the role of netrin-1 after cardiac arrest. Hypothesis: We hypothesized that the netrin-1 alleviated post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Methods: A total of sixteen male Sprague-Dawley rats (450-550 g) were randomized to two groups as follows: (1) Control group (C group); (2) Netrin-1 group (N group). Ventricular fibrillation was induced and untreated for 8 mins followed by 8 mins of CPR. Netrin-1 or saline were given at the onset of precordial compression. Ejection fraction (EF) was measured by echocardiography at baseline, 1,2,3 and 4 hours after ROSC. Results: Eight rats were resuscitated in the netrin-1 group and 7 rats were resuscitated in the saline group. In both groups, EF decreased after resuscitation when compared to the baseline (#p < 0.05). In the netrin-1 group, EF decreased from ( 68.1±3.4)% at baseline to (51.1±5.0)% at 1 hour post-resuscitation. In the saline group, EF decreased from (67.7±2.1)% at baseline to (44.5±5.3)% at 1 hr post-resuscitation. EF was better in the netrin-1 group than in the saline group at 2, 3 and 4 hours post-resuscitation (*p < 0.05) ( Figure 1). Conclusion: Netrin-1 alleviates post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.

Abstract 298: Identification of LncRNA-miRNA-mRNA Network in Myocardium After Successful Resuscitation in a Rat Model of Prolonged Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jingying Hou ◽  
Zhengfei Yang ◽  
Wanchun Tang
Keyword(s):  
Cardiac Arrest ◽  
Rat Model ◽  
Regulatory Network ◽  
High Throughput Sequencing ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Sprague Dawley ◽  
Successful Resuscitation

Introduction: Previous studies have indicated that lncRNA participates in regional myocardial ischemia-reperfusion injury (IRI). However, the lncRNA-miRNA-mRNA crosstalk in the global myocardial IRI, which is implicated in the pathophysiology of post-resuscitation myocardial dysfunction (PRMD), has still not been explored. Hypothesis: To identify lncRNA-miRNA-mRNA regulatory network in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Methods: Six male Sprague Dawley rats were randomized into sham control and ventricular fibrillation (VF)-CPR groups, with three rats in each group. VF was induced and untreated for 8 minutes. Defibrillation was attempted after 8 minutes of CPR. Heart tissue was obtained at 6 hours after resuscitation and lncRNA, miRNA and mRNA expression profiles were examined by using high-throughput sequencing. LncRNA-miRNA-mRNA interaction network was predicted and constructed. Results: Numbers of differentially expressed (DE) lncRNA, miRNA and mRNA were detected (Fig 1A). LncRNAs co-located or co-expressed target mRNAs and DE mRNAs were revealed (Fig 1B). The intersection of DE mRNAs with targeted mRNA of DE miRNAs was made (Fig 1C). A total of 129 feed forward loops were predicted as lncRNA-associated ceRNA networks,with 126 lncRNA (up)-miRNA (down)-mRNA (up) and 3 lncRNA (down)-miRNA (up)-mRNA (down) (Fig 2). Conclusions: LncRNA-miRNA-mRNAs network was predicted and constructed in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Further exploration into the specific functional roles of the ceRNA regulatory network will be conducive for the treatment of PRMD.

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