Longyuan Jiang

Quality of chest compressions during compression-only CPR: a comparative analysis following the 2005 and 2010 American Heart Association guidelines

OBJECTIVE The latest guidelines both increased the requirements of chest compression rate and depth during cardiopulmonary resuscitation (CPR), which may make it more difficult for the rescuer to provide high-quality chest compression. In this study, we investigated the quality of chest compressions during compression-only CPR under the latest 2010 American Heart Association (AHA) guidelines (AHA 2010) and its effect on rescuer fatigue. METHODS Eighty-six undergraduate volunteers were randomly assigned to perform CPR according to the 2005 AHA guidelines (AHA 2005) or AHA 2010. After the training course and theoretical examination of basic life support, eight min of compression-only CPR performance was assessed. The quality of chest compressions including rate and depth of compression was analyzed. The rescuer fatigue was evaluated by the changes of heart rate and blood lactate, and rating of perceived exertion. RESULTS Thirty-nine participants in the AHA 2005 group and 42 participants in the AHA 2010 group completed the study. Significantly greater mean chest compression depth and compression rate were both achieved in the AHA 2010 group than in the AHA 2005 group. And significantly greater rescuer fatigue was observed in the AHA 2010 group. In addition, the female in the AHA 2010 group could perform the compression rate required by the guidelines, however, significantly shallower compression depth and greater rescuer fatigue were observed when compared to the male. CONCLUSIONS The quality of chest compressions was significantly improved following the 2010 AHA guidelines, however, its more difficult for the rescuer to meet the guidelines due to the increased fatigue of rescuer.

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

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.

Ultrastructural evidence of mitochondrial abnormalities in postresuscitation myocardial dysfunction

OBJECTIVES Though there is evidence to implicate that the mitochondrion may play an important role in the development of postresuscitation myocardial dysfunction, limited data are available regarding the ultrastructural alterations of the mitochondria, mitochondrial energy-producing ability, and their relationship to postresuscitation myocardial dysfunction. This study was designed to determine whether mitochondrial abnormalities contribute to the development of postresuscitation myocardial dysfunction. METHODS Fifteen anesthetized male Sprague-Dawley rats were randomized to: (1) global myocardial ischemia/reperfusion, in which 8 min of ventricular fibrillation was induced and successful defibrillation was achieved after 6 min of cardiopulmonary resuscitation (CPR); (2) global myocardial ischemia, in which ventricular fibrillation and CPR were performed without defibrillation attempt; and (3) sham control. RESULTS Myocardial function was significantly impaired after resuscitation. Mitochondria were massively swollen in global ischemic hearts and mildly swollen in the resuscitated hearts. Concomitantly, ATP levels abruptly declined during global ischemia and partially recovered after resuscitation. Furthermore, mitochondrial abnormalities were supported by the incapability of utilizing energy substrates manifested by the accumulations of intramyocellular lipid droplets and glycogen deposits. CONCLUSIONS In this model of cardiac arrest and CPR, the presence of ultrastructural mitochondrial abnormalities, further evidenced by the incapability of utilizing energy substrates and impairment of energy-production, might, in part, contribute to the development of postresuscitation myocardial dysfunction.

Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux

ABSTRACT Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen‐glucose deprivation/reperfusion(OGD/R)‐induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP‐GFP tf‐LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up‐regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R‐induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R‐induced injury by improving lysosomal function and autophagic flux. HIGHLIGHTSOGD/R impaires lysosomes and impedes the autophagic flux in hippocampal neurons.Mild hypothermia rescues lysosomal function in neurons following OGD/R.Mild hypothermia up‐regulates the autophagic flux in neurons following OGD/R.Mild hypothermia improves mitochondrial autophagy in neurons following OGD/R.Chloroquine blocks the protective effects of mild hypothermia against OGD/R injury.

Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons

Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway. We found that, under OGD/R conditions, the pathway was down regulated, but mild hypothermia induced the reactivation of the Wnt/β-catenin signaling pathway, which had been suppressed by OGD/R injury. Mild hypothermia also caused the down regulation of the expression of apoptosis promoting proteins (Bax cleaved caspase-3), up-regulated the expression of apoptosis inhibiting proteins (Bcl-2), and ameliorated OGD/R injury-induced apoptosis. The protective effects of mild hypothermia were blocked by DKK1 (an antagonist of the canonical Wnt signaling pathway). Taken together, these results indicate that the Wnt/β-catenin signaling pathway mediates the protective effects of mild hypothermia against OGD/R-induced apoptosis. Our study provides evidence that mild hypothermia reactivates the Wnt/β-catenin signaling pathway, which is suppressed by OGD/R injury, in hippocampal neurons and protects neurons from OGD/R-induced apoptosis via the reactivation of the Wnt/β-catenin signaling pathway, ultimately suggesting that mild hypothermia could have therapeutic effects on OGD/R-induced apoptosis.

Activation of Pyruvate Dehydrogenase Activity Bydichloroacetate Improves Survival and Neurologic Outcomes After Cardiac Arrest in Rats

ABSTRACT No pharmacological interventions are currently available to provide neuroprotection for patients suffering from cardiac arrest. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase inhibitor, which activates pyruvate dehydrogenase (PDH), and increases cell adenosine triphosphate (ATP) production by promoting influx of pyruvate into the Krebs cycle. In this study, we investigated the effects of DCA on post-resuscitation neurological injury in an asphyxial cardiac arrest rat model. Asphyxial cardiac arrest was established by endotracheal tube clamping. A total of 111 rats were randomized into three groups: Sham group, Control group, and DCA intervention group. Animals in DCA intervention group were intraperitoneally administered DCA with a loading dose of 80 mg/kg at 15 min after return of spontaneous circulation (ROSC), whereas rats in the Control group received equivalent volume of saline. DCA treatment increased 3-day survival time, and reduced neurologic deficit scores at 24, 48, and 72 h after ROSC. It also attenuated cellular apoptosis and neuronal damage in the hippocampal cornuammonis one region by hematoxylin-eosin staining and TdT-mediated dUTP nick-end labeling assay. In addition, DCA reduced the messenger RNA expression of tumor necrosis factor &agr; and interleukin 1&bgr; in brain hippocampus and cortex after ROSC. Furthermore, DCA treatment significantly increased ATP production, PDH activity, and decreased blood glucose, lactate, and brain pyruvate levels after ROSC. Our results suggested that DCA has neuroprotective effects on brain injury after cardiac arrest, and its salutary effects were associated with an increase of mitochondrial energy metabolism in the brain through activation of PDH activity.

Comparison of continuous compression with regular ventilations versus 30:2 compressions-ventilations strategy during mechanical cardiopulmonary resuscitation in a porcine model of cardiac arrest

Background A compression-ventilation (C:V) ratio of 30:2 is recommended for adult cardiopulmonary resuscitation (CPR) by the current American Heart Association (AHA) guidelines. However, continuous chest compression (CCC) is an alternative strategy for CPR that minimizes interruption especially when an advanced airway exists. In this study, we investigated the effects of 30:2 mechanical CPR when compared with CCC in combination with regular ventilation in a porcine model. Methods Sixteen male domestic pigs weighing 39±2 kg were utilized. Ventricular fibrillation was induced and untreated for 7 min. The animals were then randomly assigned to receive CCC combined with regular ventilation (CCC group) or 30:2 CPR (VC group). Mechanical chest compression was implemented with a miniaturized mechanical chest compressor. At the same time of beginning of precordial compression, the animals were mechanically ventilated at a rate of 10 breaths-per-minute in the CCC group or with a 30:2 C:V ratio in the VC group. Defibrillation was delivered by a single 150 J shock after 5 min of CPR. If failed to resuscitation, CPR was resumed for 2 min before the next shock. The protocol was stopped if successful resuscitation or at a total of 15 min. The resuscitated animals were observed for 72 h. Results Coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow in the VC group were similar to those achieved in the CCC group during CPR. No significant differences were observed in arterial blood gas parameters between two groups at baseline, VF 6 min, CPR 4 min and 30, 120 and 360 min post-resuscitation. Although extravascular lung water index of both groups significantly increased after resuscitation, no distinct difference was found between CCC and VC groups. All animals were successfully resuscitated and survived for 72 h with favorable neurologic outcomes in both groups. However, obviously more numbers of rib fracture were observed in CCC animals in comparison with VC animals. Conclusions There was no difference in hemodynamic efficacy and gas exchange during and after resuscitation, therefore identical 72 h survival with intact neurologic function was observed in both VC and CCC groups. However, the incidence of rib fracture increases during the mechanical CPR strategy of CCC combined with regular ventilations.

Carbon Monoxide Improves Neurologic Outcomes by Mitochondrial Biogenesis after Global Cerebral Ischemia Induced by Cardiac Arrest in Rats

Mitochondrial dysfunction contributes to brain injury following global cerebral ischemia after cardiac arrest. Carbon monoxide treatment has shown potent cytoprotective effects in ischemia/reperfusion injury. This study aimed to investigate the effects of carbon monoxide-releasing molecules on brain mitochondrial dysfunction and brain injury following resuscitation after cardiac arrest in rats. A rat model of cardiac arrest was established by asphyxia. The animals were randomly divided into the following 3 groups: cardiac arrest and resuscitation group, cardiac arrest and resuscitation plus carbon monoxide intervention group, and sham control group (no cardiac arrest). After the return of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the rats. This treatment also decreased the number of damaged neurons in the hippocampus CA1 area and increased the brain mitochondrial activity. In addition, it increased mitochondrial biogenesis by increasing the expression of biogenesis factors including peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, nuclear respiratory factor-2 and mitochondrial transcription factor A. Thus, this study showed that carbon monoxide treatment alleviated brain injury after cardiac arrest in rats by increased brain mitochondrial biogenesis.

Inhibition of dynamin-related protein 1 has neuroprotective effect comparable with therapeutic hypothermia in a rat model of cardiac arrest

&NA; Dynamin‐related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi‐1 improves survival and attenuates cerebral ischemic injury after cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post‐resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: mdivi‐1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12). The rats in the mdivi‐1 treatment group were received intravenously 1.2 mg/kg of mdivi‐1 at 1 minute after the return of spontaneous circulation (ROSC). In rats in hypothermia group, rapid cooling was initiated at 5 minutes after resuscitation, and the core temperature was maintained to 33 ± 0.5°C for 2 hours. The results showed that both Drp1 inhibition and therapeutic hypothermia increased 3‐day survival time (all P < 0.05) and improved neurologic function up to 72 hours post cardiac arrest. In addition, both Drp1 inhibition and therapeutic hypothermia decreased cell injury, apoptosis in hippocampal cornu ammonis 1 region and brain mitochondrial dysfunction including adenosine triphosphate production, reactive oxygen species and mitochondrial membrane potential after cardiac arrest. Moreover, therapeutic hypothermia decreased mitochondrial Drp1 expression and mitochondrial fission after cardiac arrest. In conclusion, inhibition of Drp1 has a similar effect to therapeutic hypothermia on neurologic outcome after resuscitation in this cardiac arrest rat model, and the neuroprotective effects of therapeutic hypothermia are associated with inhibition of mitochondrial fission.