The Effects of Carvedilol Administration on Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest Induced by Airway Obstruction

Recent studies have showed that hypoventilation during cardiopulmonary resuscitation (CPR) improved the rates of return of spontaneous circulation (ROSC) and prognosis. However, there are few studies about the ventilation strategies during CPR in cardiac arrest caused by airway obstruction. To compare the effects of the three ventilation strategies during CPR in an animal model of cardiac arrest induced by airway obstruction, we investigated the rates of ROSC, survival rates, plasma cytokine levels, and lactate levels. thirty-six male Sprague Dawley rats were anesthetized with intraperitoneal injection of pentobarbital. Cardiac arrest was induced by airway obstruction. After 3 minutes of cardiac arrest, animals were randomized to receive one of the three ventilation strategies during CPR (n = 12 per group): normoventiraion (28 breaths/min), hypoventilation (14 breaths/min), or no-ventilation. The rates of chest compression (CC) was 240 –260 compressions/min and the depth of CC adjusted to maintain mean arterial pressure more than 25 mmHg in all groups. After 5 minutes of CPR, epinephrine (0.02 mg/kg) was administered, and all rats were ventilated at the rates of 28 breaths/min in FiO2 1.0. The rates of ROSC were 83%, 58%, 0% for the normoventilation, hypoventilation, and no-ventilation groups, respectively. The PaCO2 levels immediately after ROSC were 74mmHg and 88 mmHg for the normoventilation, and hypoventilation groups, respectively. The increases of plasma cytokine (TNF-a, and IL-6) levels and lactate levels after ROSC in the normoventilation group were significantly less than those in the hypoventilation group. The present study showed that normoventilation during CPR improved the rates of ROSC and the survival rates after ROSC in the animal cardiac arrest model induced by airway obstruction. Moreover, normoventilation attenuated the elevation of cytokine and lactate responses. These findings suggest that ventilation may be necessary during CPR in cardiac arrest caused by airway obstruction.

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The Effect of a Modified Constant Flow Insufflation of Oxygen during Cardiopulmonary Resuscitation in a Rat Model of Respiratory Cardiac Arrest on Arterial Oxygenation, Alveolar Barotrauma, and Brain Tissue Injury

Emergency Medicine International ◽

10.1155/2020/8913571 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yoonje Lee ◽

Sang-hyun Lee ◽

Hyuk Joong Choi ◽

Jinkyu Park ◽

Sejin Hwang ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Rat Model ◽

Continuous Flow ◽

Positive Pressure Ventilation ◽

Respiratory Arrest ◽

Intermittent Positive Pressure Ventilation ◽

Positive Pressure ◽

Alveolar Wall ◽

Arterial Blood

Aim. Intermittent positive pressure ventilation (IPPV) can adversely affect cardiopulmonary resuscitation outcomes by increasing the intrathoracic pressure. Continuous flow insufflation of oxygen (CFIO) has been investigated as a potential alternative, but evidence supporting its superiority over intermittent positive pressure ventilation in cases of cardiac arrest is scant. The aim of the current study was to compare the effects of continuous flow insufflation of oxygen using a one-way valve during cardiopulmonary-resuscitation with intermittent positive pressure ventilation in a rat model of respiratory arrest. Methods. Male Sprague-Dawley rats weighing 400∼450 g (from minimum to maximum) were randomly assigned to either a sham, IPPV, or CFIO group (n = 10 per group). Respiratory arrest was induced by blocking the endotracheal tube. Arterial blood gas analysis was performed during cardiopulmonary resuscitation to compare the oxygenation levels. Tissues were then harvested to compare the degrees of pulmonary barotrauma and ischemic brain injury. Results. Return of spontaneous circulation was observed in 6/10 rats in the IPPV group and 5/10 in the CFIO group. During cardiopulmonary resuscitation, the mean PaO2 was significantly higher in the CFIO group (83.10 mmHg) than in the IPPV group (56.10 mmHg). Lung biopsy revealed more inflammatory cells and marked thickening of the alveolar wall in the IPPV group; the group also exhibited a higher frequency of neuroglial cells and apoptotic bodies of pyramidal cells, resulting from ischemic injury. Conclusion. In a rat model of respiratory arrest, CFIO using a one-way valve resulted in a greater level of oxygenation and less lung and brain injuries than with IPPV.

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

BioMed Research International ◽

10.1155/2014/192769 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 7

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.

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Effects of sodium hydrosulfide on intestinal mucosal injury in a rat model of cardiac arrest and cardiopulmonary resuscitation

Life Sciences ◽

10.1016/j.lfs.2013.05.012 ◽

2013 ◽

Vol 93 (1) ◽

pp. 24-29 ◽

Cited By ~ 16

Author(s):

Hao Pan ◽

Di Chen ◽

Beibei Liu ◽

Xuemeng Xie ◽

Jincheng Zhang ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Rat Model ◽

Mucosal Injury ◽

Sodium Hydrosulfide ◽

Intestinal Mucosal Injury

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Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia

Journal of Applied Physiology ◽

10.1152/japplphysiol.01487.2005 ◽

2006 ◽

Vol 101 (4) ◽

pp. 1091-1096 ◽

Cited By ~ 15

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.

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The incidence of acute kidney injury following cardiac arrest and cardiopulmonary resuscitation in a rat model

Renal Failure ◽

10.1080/0886022x.2019.1596819 ◽

2019 ◽

Vol 41 (1) ◽

pp. 278-283

Author(s):

Zhao-Yin Fu ◽

Zhi-Jiang Wu ◽

Jun-Hui Zheng ◽

Tao Qin ◽

Ye-Gui Yang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Rat Model ◽

Kidney Injury

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Cerebral and myocardial mitochondrial injury differ in a rat model of cardiac arrest and cardiopulmonary resuscitation

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111743 ◽

2021 ◽

Vol 140 ◽

pp. 111743

Author(s):

Xianfei Ji ◽

Jennifer L. Bradley ◽

Guanghui Zheng ◽

Weiwei Ge ◽

Jing Xu ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Rat Model ◽

Mitochondrial Injury

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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 ◽

10.1161/circ.142.suppl_4.142 ◽

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.

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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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