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

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.

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

Circulation ◽

10.1161/circ.142.suppl_4.211 ◽

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.

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

Circulation ◽

10.1161/circ.130.suppl_2.148 ◽

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.

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

Circulation ◽

10.1161/circ.132.suppl_3.10773 ◽

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.

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Abstract 120: Artesunate Reduces the Severity of Post-Resuscitation Myocardial and Cerebral Dysfunction

Circulation ◽

10.1161/circ.142.suppl_4.120 ◽

2020 ◽

Vol 142 (Suppl_4) ◽

Author(s):

Hui Li ◽

Cheng Cheng ◽

Lian Liang ◽

Tao Jin ◽

Guozhen Zhang ◽

...

Keyword(s):

Survival Rate ◽

Rat Model ◽

Plasma Levels ◽

Myocardial Dysfunction ◽

Spontaneous Circulation ◽

Cerebral Function ◽

Sprague Dawley ◽

Cerebral Dysfunction ◽

Tnf Α ◽

Poor Outcomes

Introduction: Artesunate (ART) possesses anti-inflammatory activity, which can mitigate the systemic inflammatory response in poor outcomes of cardiac arrest (CA). We investigated the effects of ART on myocardial and cerebral function, duration of survival, and inflammation in a rat model of CA and cardiopulmonary resuscitation (CPR). Hypothesis: ART reduces the severity of post resuscitation myocardial and cerebral dysfunction by alleviating inflammation in a rat model of CA and CPR. Methods: 30 male Sprague-Dawley rats weighing between 450g-550g were randomized into 3 groups: Sham (S), Control (C), and Artesunate (A). C and A were divided into subgroups: survival and non-survival (n=6). Ventricular fibrillation (VF) was induced and untreated for 6 min. A 4J defibrillation was attempted after 8 min of CPR. Phosphate buffer (1ml/kg, pH 7.9-8.1) or ART (2.4mg/kg), was administered at return of spontaneous circulation (ROSC). Myocardial function was measured at baseline and every hour for 4h post ROSC. Plasma levels of IL-6, TNF-α and cTnI were detected at baseline and 4h after ROSC. Survival animals were observed for an additional 72h. Neurologic deficit scores were recorded daily. Results: ART reduced the severity of post-resuscitation myocardial dysfunction compared to C. It attenuated IL-6, TNF-α and cTnI plasma levels 4h after ROSC (p<0.05) (Fig. 1). Post-resuscitation cerebral function and survival rate also improved significantly (p<0.05) (Fig. 2). Conclusion: ART reduces the severity of post-resuscitation myocardial and cerebral dysfunction, improves survival rate and attenuates inflammation in a rat of model of CA and CPR.

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

Circulation ◽

10.1161/circ.138.suppl_2.104 ◽

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.

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The effect of high-dose intramuscular epinephrine on the recovery of spontaneous circulation in an asphyxia‐induced cardiac arrest rat model

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01917-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Daesung Lim ◽

Soo Hoon Lee ◽

Dong Hoon Kim ◽

Changwoo Kang ◽

Jin Hee Jeong ◽

...

Keyword(s):

Cardiac Arrest ◽

Rat Model ◽

Saline Group ◽

Spontaneous Circulation ◽

Rank Test ◽

High Dose ◽

Sprague Dawley ◽

Epinephrine Administration ◽

Arterial Blood ◽

Induced Cardiac Arrest

Abstract Background Obtaining vascular access can be challenging during resuscitation following cardiac arrest, and it is particularly difficult and time-consuming in paediatric patients. We aimed to compare the efficacy of high-dose intramuscular (IM) versus intravascular (IV) epinephrine administration with regard to the return of spontaneous circulation (ROSC) in an asphyxia-induced cardiac arrest rat model. Methods Forty-five male Sprague-Dawley rats were used for these experiments. Cardiac arrest was induced by asphyxia, and defined as a decline in mean arterial pressure (MAP) to 20 mmHg. After asphyxia-induced cardiac arrest, the rats were randomly allocated into one of 3 groups (control saline group, IV epinephrine group, and IM epinephrine group). After 540 s of cardiac arrest, cardiopulmonary resuscitation was performed, and IV saline (0.01 cc/kg), IV (0.01 mg/kg, 1:100,000) epinephrine or IM (0.05 mg/kg, 1:100,000) epinephrine was administered. ROSC was defined as the achievement of an MAP above 40 mmHg for more than 1 minute. Rates of ROSC, haemodynamics, and arterial blood gas analysis were serially observed. Results The ROSC rate (61.5%) of the IM epinephrine group was less than that in the IV epinephrine group (100%) but was higher than that of the control saline group (15.4%) (log-rank test). There were no differences in MAP between the two groups, but HR in the IM epinephrine group (beta coefficient = 1.02) decreased to a lesser extent than that in the IV epinephrine group with time. Conclusions IM epinephrine induced better ROSC rates compared to the control saline group in asphyxia-induced cardiac arrest, but not compared to IV epinephrine. The IM route of epinephrine administration may be a promising option in an asphyxia-induced cardiac arrest.

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Abstract 11100: Effect of Different Oxygen Concentrations on Post Resuscitation Myocardial Oxidative Stress and Myocardial Function in a Rat Model of CPR

Circulation ◽

10.1161/circ.130.suppl_2.11100 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Shen Zhao ◽

Jie Qian ◽

Jiangang Wang ◽

Ping Gong ◽

Zhengfei Yang ◽

...

Keyword(s):

Lipid Peroxidation ◽

Myocardial Function ◽

Myocardial Dysfunction ◽

Prostaglandin F2α ◽

Blood Gases ◽

Spontaneous Circulation ◽

Enzyme Linked Immunosorbent Assay ◽

Sprague Dawley ◽

Myocardial Oxidative Stress ◽

Inspired Oxygen

Background: Lipid peroxidation induced by oxygen free radicals plays a prominent role in myocardial injury after global ischemia. The present study investigated whether ventilation with lower concentration of inspired oxygen would decrease the severity of myocardial lipid peroxidation and post resuscitation myocardial dysfunction. Methods: Ventricular fibrillation was induced and untreated for 8 mins in 46 male Sprague-Dawley rats. Defibrillation was attempted after 8 mins of CPR. The animals were randomized into 3 groups: mechanical ventilation with 100% O2, 50% O2 or 21% O2 during CPR and one hr following return of spontaneous circulation. Normoxic ventilation was maintained thereafter. The level of 8-iso-Prostaglandin F2α (8-iso-PGF2α) in myocardium was evaluated using the enzyme-linked immunosorbent assay (ELISA). Blood gases, post resuscitation myocardial function and the duration of survival were monitored in all animals. Results: Compared with the 100% and 21% groups, the 50% group showed a lower 8-iso-PGF2α level at 4 hrs post resuscitation (Table). Significantly greater oxygen extraction rate, lower lactate, better myocardial ejection fraction and myocardial performance index were observed in the 50% group (Table). A significantly shorter duration of survival was observed in the 21% group when compared with the other two groups (Table). There was a trend in the 50% group towards an increased duration of survival when compared with the 100% group. Conclusions: In a rat cardiac arrest model, ventilation with 50% inspired oxygen during early post-ischemic reperfusion contributed to a decreased lipid peroxidation, a better oxygenation, myocardial function and duration of survival.

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Abstract 179: Effects of Necrosulfonamide on Post-Resuscitation Survival and Neurological Function in a Rat Model of Cardiac Arrest

Circulation ◽

10.1161/circ.140.suppl_2.179 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

Fenglian He ◽

Guanghui Zheng ◽

Juntao Hu ◽

Weiwei Ge ◽

Xianfei Ji ◽

...

Keyword(s):

Cardiac Arrest ◽

Rat Model ◽

Interleukin 1 ◽

Kinase Domain ◽

Spontaneous Circulation ◽

Neurological Function ◽

Protective Effects ◽

Sprague Dawley ◽

Injection Duration ◽

Cerebral Ischemia And Reperfusion

Introduction: Gasdermin D (GSDMD), a previously unknown protein, serves as a key effector in pyroptosis and its inhibition has protective effects during cerebral ischemia and reperfusion. Necrosulfonamide (NSA) specifically blocks the mixed lineage kinase domain-like pseudo kinase (MLKL), which directly binds to GSDMD preventing pyroptotic cell death and interleukin-1 (IL-1) release. In this study, we investigated the effects of NSA on survival and neurological function after cardiac arrest and resuscitation. Hypothesis: Administration of NSA following cardiopulmonary resuscitation (CPR) will improve survival and neurological function in a rat model of cardiac arrest. Methods: Twelve male Sprague-Dawley rats weighting between 450-550g were utilized. Ventricular fibrillation was induced and untreated for 6 min followed by defibrillation after 8 min of CPR. Animals were then randomized into two groups: NSA and control. NSA (10mg/kg) or vehicle was administered 5 minutes after restoration of spontaneous circulation (ROSC) by intraperitoneal injection. Duration of survival and neurological deficit scores were recorded at 24, 48, and 72 hours after ROSC. Results: All animals were resuscitated successfully. Duration of survival was significantly longer in the NSA group compared to control (p<0.05, Figure 1). The severity of post-resuscitation cerebral dysfunction was significantly reduced in the NSA group compared to control (p<0.05, Figure 2). Conclusion: Administration of NSA after ROSC improves post-resuscitation survival and neurological function in a rat model of cardiac arrest.

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Abstract 10770: Curcumin Mitigates the Severity of Post-Resuscitation Myocardial Dysfunction Caused by Epinephrine in a Rat Cardiac Arrest Model

Circulation ◽

10.1161/circ.132.suppl_3.10770 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Zhengfei Yang ◽

Jiangang Wang ◽

Lu Yin ◽

Shen Zhao ◽

Ziren Tang ◽

...

Keyword(s):

Cardiac Arrest ◽

Placebo Group ◽

Ventricular Fibrillation ◽

Myocardial Function ◽

Myocardial Dysfunction ◽

Sprague Dawley ◽

Successful Resuscitation ◽

Sprague Dawley Rats ◽

Group 3 ◽

Group 2

Introduction: Epinephrine significantly increases the severity of post-resuscitation myocardial dysfunction (PRMD) and reduces the duration of survival. The cardioprotective effect of curcumin against catecholamine-induced cardiotoxicity has been established. In the present study, we investigated the effects of curcumin on PRMD caused by epinephrine in a rat model of cardiac arrest. Hypothesis: Curcumin reduces the severity of PRMD caused by epinephrine. Methods: Twenty-four male Sprague-Dawley rats weighing between 450-550g were randomized into three groups: 1) Placebo group; 2) Epinephrine (20ug/kg) group; 3) Curcumin (100 mg/kg) pretreatment + epinephrine (20ug/kg) group. Ventricular fibrillation (VF) was then 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. Results: All animals except for two in the placebo group were resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. Significantly worse myocardial function was observed in the Epinephrine group in comparison with the two other groups (Figure). However, myocardial function was significantly better in the animals treated with curcumin when compared with those in the two other groups (Figure). Conclusion: In a rat cardiac arrest model, curcumin reduced the severity of PRMD caused by epinephrine.

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Modification of T cells function after restoration of spontaneous circulation in a rat model of cardiac arrest

10.1101/560789 ◽

2019 ◽

Author(s):

Chunlin Xing ◽

Yang Chen ◽

Xuemei Zhu ◽

Guoping Lu ◽

Weiming Chen

Keyword(s):

T Cells ◽

Cardiac Arrest ◽

Rat Model ◽

Spontaneous Circulation ◽

Control Group ◽

Sprague Dawley ◽

Surface Molecules ◽

Number Of Patients ◽

Ifn Γ ◽

Inhibitory Molecules

AbstractCardiac arrest (CA) is a prominent cause of mortality worldwide. A large number of patients after post-cardiac arrest is often associated with a phase of impaired immunity. Through an asphyxial cardiac arrest rat model, we investigate the peripheral blood T cells subsets and the expressions of surface molecules after restoration of spontaneous circulation (ROSC). Sprague-Dawley rats (weight, 300-400 g) were randomly divided into cardiac arrest (CA) group and sham-operated group. CA group rats were induced by 6 minutes of asphyxia. After successful ROSC, 24 surviving rats in two groups were randomly assigned to be sacrificed (n = 8 per subgroup) at 3, 24 and 72 h. The proportion of T cells and CD4+, CD8+ subsets as well as the expression of surface molecules (CTLA-4, PD-1, CD28) on T cells were identified by flow cytometry. The protein concentrations of cytokines (TNF-α, IL-6, IL-10, IL-4, IFN-γ, IL-17A) in serum were measured by ELISA. Compared with sham-operated control group, CD3+ lymphocytes in CA group were significantly decreased at 24 and 72 h post-ROSC. The expression levels of CD28, PD-1, and CTLA-4 on T cells were markedly increased in CA groups at 24 h post-ROSC. Additionally, the concentrations of IFN-γ were significantly declined, while IL-4 was markedly elevated in the CA group at 24 and 72 h post-ROSC. T cells function is moderately changed after CA, which is associated with decreased percentage of T cells, the upregulation of co-inhibitory molecules, and the shift from T helper (Th) 1 to Th2.

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