Abstract 174: Effects of Melatonin (N-Acetyl-5-Methoxytryptamine) on Inflammation and Cerebral Microcirculation After Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Juntao Hu ◽  
Guanghui Zheng ◽  
Fenglian He ◽  
Weiwei Ge ◽  
Jing Xu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Rat Model ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Flow Index ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Tnf Α

Introduction: Cerebral ischemia-reperfusion injury produces inflammation and cerebral microcirculatory dysfunction after cardiopulmonary resuscitation (CPR). Melatonin (N-acetyl-5-methoxytryptamine) has both anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of melatonin on inflammation and cerebral microcirculation after cardiopulmonary resuscitation in a rat model of cardiac arrest. Hypothesis: Melatonin decreases the systemic inflammatory response after cardiopulmonary resuscitation and will preserve cerebral microcirculation in a rat model of cardiac arrest. Method: Eighteen male Sprague Dawley rats weighing between 450-550 g were randomized into three groups: 1) sham: no ventricular fibrillation (VF) and CPR; 2) CPR control: untreated VF for 6 min followed by 8 min CPR; 3) CPR+melatonin: untreated VF for 6 min followed by 8 min CPR. Melatonin (10 mg/kg) was administered intraperitoneal (IP) in line with hypoxia-ischemia animal studies after return of spontaneous circulation (ROSC). Serum TNF- α, IL-1 β and cerebral microcirculation were measured at baseline and 6 h following ROSC. Result: Serum TNF-α and IL-1β were significantly lower in the CPR+melatonin group at 6h after ROSC compared to CPR controls ( p <0.01, Fig. 1). Animals treated with melatonin had improved cerebral microcirculation including perfused vessel density (PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI) compared to control animals ( p <0.05, Fig. 2). Conclusion: In a rat model of cardiac arrest, melatonin reduced systemic inflammation and preserved cerebral microcirculation following resuscitation.

Abstract 173: The Neuroprotective Effect Of JZL184 is Comparable With Therapeutic Hypothermia in a Rat Model of Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
Jennifer Bradley ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Rat Model ◽  
Neuroprotective Effect ◽  
Experimental Studies ◽  
Flow Index ◽  
Protective Effects ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Introduction: JZL184 is a synthetic monoacylglycerol lipase inhibitor that reduces brain edema, infarct size and alleviates inflammation following cerebral ischemia in experimental studies. In this study, we compared its cerebral protective effects with therapeutic hypothermia following cardiopulmonary resuscitation (CPR) in a rat model. Hypothesis: JZL184 will have similar neuroprotective effects to therapeutic hypothermia after cardiac arrest (CA) by reducing brain and blood brain barrier (BBB) injury and preserving cerebral microcirculation following CPR. Methods: Thirty six male Sprague-Dawley rats weighing between 450-550 g were randomized: 1) control 2) hypothermia 3) JZL184. Ventricular fibrillation was induced and untreated for 6 min for all rats. Resuscitation was attempted with a 4 Joule defibrillation after 8 min of CPR. Immediately following resuscitation, either hypothermia (33+0.5 o C) or JZL184 (16 mg/k, IP) was administered. Cerebral microcirculation, S-100β, NSE and Evan’s Blue (EB) concentrations were analyzed at 6hrs after resuscitation. Results: NSE and S-100β levels were higher in control compared to hypothermia and JZL18 at 6hr post ROSC (p < 0.001) (Fig. 1). Compared with control, there was a significant decrease in brain permeability to EB in Hypothermia and JZL184 after 6hr post ROSC (p<0.001) (Fig. 2). Microvascular flow index (MFI) was reduced in control compared with hypothermia and JZL184 6hr post ROSC (p <0.01). Conclusions: JZL184 administered following resuscitation reduced brain and BBB injury and preserved cerebral microcirculation at 6 hr post arrest to the same extent as hypothermia in a rat model of 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.

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 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.

Abstract 21: Effects of the Selective NLRP3-Inflammasome Inhibitor MCC950 on Post-Resuscitation Myocardial and Cerebral Function in a Rat Model of Cardiopulmonary Resuscitation

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Guanghui Zheng ◽  
Jing Xu ◽  
Fenglian He ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Rat Model ◽  
Nlrp3 Inflammasome ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Sprague Dawley ◽  
Sublingual Microcirculation ◽  
Cerebral Dysfunction

Introduction: NLRP3 inflammasome mediated pyroptosis has been demonstrated to increase myocardial and cerebral ischemia/reperfusion injury. MCC950 is a newly developed highly selective inhibitor of the NLRP3 inflammasome. Hypothesis: MCC950 administered following resuscitation will reduce the severity of post-resuscitation myocardial and cerebral dysfunction and improve duration of survival in a rat model of CPR. Methods: 15 male Sprague-Dawley rats weighting between 450-550 g were randomized into three groups: 1) MCC950 2) Control 3) Sham. Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was then initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. Either MCC950 (10mg/kg) or vehicle was administered intraperitoneal (IP) in line with cardiac injury animal studies immediately after return of spontaneous circulation (ROSC). Sham underwent the same surgical procedure without VF and CPR. Sublingual microcirculation was measured at baseline (BL), 3, 6 and 48 hrs after ROSC. Ejection fraction (EF) was measured at BL, 1, 3, 6 and 48 hrs after ROSC. Neurologic Deficit Score (NDS) was recorded at 48 hrs after resuscitation. Results: Post-resuscitation ejection fraction and perfused sublingual vessel density were greater in MCC950 compared to control (p<0.05). NDS was also improved in MCC950 compared to control (110 vs 425, p<0.05). Survival at 48 hrs after ROSC was greater in MCC950 (4/5 vs 1/5, p<0.05). Conclusion: Administration of MCC950 following ROSC mitigates post-resuscitation myocardial and cerebral dysfunction, improves sublingual microcirculation and duration of survival in a rat model of CPR.

scholarly journals Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Gang Chen ◽  
Jingru Li ◽  
Jianjie Wang ◽  
Bihua Chen ◽  
Yongqin Li
Keyword(s):  
Cardiac Arrest ◽  
Rat Model ◽  
Animal Studies ◽  
Onset Time ◽  
Quantitative Eeg ◽  
Permutation Entropy ◽  
Sprague Dawley ◽  
Ctrl Group ◽  
Neurological Outcomes ◽  
Prognostic Accuracy

Background. Electroencephalography (EEG) is commonly used to assess the neurological prognosis of comatose patients after cardiac arrest (CA). However, the early prognostic accuracy of EEG may be affected by postresuscitation interventions. Recent animal studies found that hydrogen inhalation after CA greatly improved neurological outcomes by selectively neutralizing highly reactive oxidants, but the effect of hydrogen inhalation on EEG recovery and its prognostication value are still unclear. The present study investigated the effects of hydrogen inhalation on early postresuscitation EEG characteristics in an asphyxial CA rat model. Methods. Cardiopulmonary resuscitation was initiated after 5 min of untreated CA in 40 adult female Sprague-Dawley rats. Animals were randomized for ventilation with 98% oxygen plus 2% hydrogen (H2) or 98% oxygen plus 2% nitrogen (Ctrl) under normothermia for 1 h. EEG characteristics were continuously recorded for 4 h, and the relationships between quantitative EEG characteristics and 96 h neurological outcomes were investigated. Results. No differences in baseline and resuscitation data were observed between groups, but the survival rate was significantly higher in the H2 group than in the Ctrl group (90% vs. 40%, P<0.01). Compared to the Ctrl group, the H2 group showed a shorter burst onset time (21.85 [20.00–23.38] vs. 25.70 [22.48–30.05], P<0.01) and time to normal trace (169.83 [161.63–208.55] vs. 208.39 [186.29–248.80], P<0.01). Additionally, the burst suppression ratio (0.66 ± 0.09 vs. 0.52 ± 0.17, P<0.01) and weighted‐permutation entropy (0.47 ± 0.16 vs. 0.34 ± 0.13, P<0.01) were markedly higher in the H2 group. The areas under the receiver operating characteristic curves for the 4 EEG characteristics in predicting survival were 0.82, 0.84, 0.88, and 0.83, respectively. Conclusions. In this asphyxial CA rat model, the improved postresuscitation EEG characteristics for animals treated with hydrogen are correlated with the better 96 h neurological outcome and predicted survival.

Endogenous BMP-4/ROS/COX-2 Mediated IPC and Resveratrol Alleviated Brain Damage

2019 ◽  
Vol 25 (9) ◽  
pp. 1030-1039 ◽  
Author(s):  
Ying Yan ◽  
Fei Tong ◽  
Jianer Chen
Keyword(s):  
Intraperitoneal Injection ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
B Cell Lymphoma ◽  
Sprague Dawley ◽  
Expression Levels ◽  
Tnf Α ◽  
Cox 2 ◽  
Stress Damage ◽  
Factor Α

The objective of the study was to examine the therapeutic role of combined ischemic preconditioning (IPC) and resveratrol (RES) on brain ischemia/reperfusion injury (BI/RI) by modulating endogenous bone morphogenetic protein-4 (BMP-4)/reactive oxygen species (ROS)/cyclooxygenase-2 (COX-2) in rats. Sprague Dawley (SD) rats were pretreated with 20 mg/kg RES (20 mg/kg RES was administered once a day via intraperitoneal injection 7 days prior to the I/R procedure) and IPC (equal volumes of saline were administered once a day by intraperitoneal injection over 7 days, and the bilateral common carotid arteries were separated for clamp 5 minutes followed by 5 minutes of reperfusion prior to the I/R procedure), and then subjected to 2 hours of ischemia and 22 hours of reperfusion. Blood and cerebral tissues were collected, cerebral pathological injuries and infarct sizes were investigated, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured, the activities of superoxide dismutase (SOD) and ROS were calculated, the contents of methane dicarboxylic aldehyde (MDA), IL-6, TNF-α and hemodynamic change were estimated, and expression levels of b-cell lymphoma-2 (Bcl-2), bcl-2-associated x (Bax), BMP-4 and COX-2 were assessed in cerebral tissues. IPC, RES and a combination of IPC and RES preconditioning ameliorated the pathological damage and infarct sizes, reduced cerebral oxidative stress damage, alleviated inflammatory damage, restrained apoptosis, and downregulated the expression levels of BMP-4 and COX-2 compared with those of the ischemia/reperfusion (I/R) group. This study suggested a combined strategy that could enhance protection against BI/RI in clinical brain disease.

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.

scholarly journals Estrogen prevents intestinal inflammation after trauma-hemorrhage via downregulation of angiotensin II and angiotensin II subtype I receptor

2008 ◽  
Vol 295 (5) ◽  
pp. G1131-G1137 ◽  
Author(s):  
Jianguo Chen ◽  
Shaolong Yang ◽  
Shunhua Hu ◽  
Mashkoor A. Choudhry ◽  
Kirby I. Bland ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Intestinal Inflammation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion Molecule ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Total Blood ◽  
Tnf Α ◽  
Salutary Effect

Although angiotensin II (Ang II) plays a key role in development of organ ischemia-reperfusion injury, it remains unclear whether it is involved in development of intestinal injury following trauma-hemorrhage (T-H). Studies have shown that 17β-estradiol (E2) administration following T-H improves small intestinal blood flow; however, it is unclear whether Ang II plays a role in this E2-mediated salutary effect. Male Sprague-Dawley rats underwent laparotomy and hemorrhagic shock (removal of 60% total blood volume, fluid resuscitation after 90 min). At onset of resuscitation, rats were treated with vehicle, E2, or E2 and estrogen receptor antagonist ICI 182,780 (ICI). A separate group of rats was treated with Ang II subtype I receptor (AT1R) antagonist losartan. At 24 h after T-H, plasma Ang II, IL-6, TNF-α, intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 levels, myeloperoxidase (MPO) activity, and AT1R expression were determined. T-H significantly increased plasma and intestinal Ang II, IL-6, TNF-α levels, intestinal ICAM-1, CINC-1, CINC-3 levels, MPO activity, and AT1R protein compared with shams. E2 treatment following T-H attenuated increased intestinal MPO activity, Ang II level, and AT1R protein expression. ICI administration abolished the salutary effects of E2. In contrast, losartan administration attenuated increased MPO activity without affecting Ang II and AT1R levels. Thus Ang II plays a role in producing small intestine inflammation following T-H, and the salutary effects of E2 on intestinal inflammation are mediated in part by Ang II and AT1R downregulation.

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