Zitong Huang

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.

Intravenous infusion of bone marrow mesenchymal stem cells improves myocardial function in a rat model of myocardial ischemia.

Objective:We investigated the effects of three different sites for delivery of bone marrow mesenchymal stem cells (MSCs) in a rat model of myocardial ischemia. Design:Prospective, randomized, controlled study. Setting:University affiliated research institute. Subjects:Male Sprague-Dawley rats. Interventions:A thoracotomy was performed under general anesthesia. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery. One month later, animals were randomized to receive 5 × 106 MSCs labeled with PKH26 in phosphate buffer solution or phosphate buffer solution alone as a placebo by injection into right femoral vein, directly into the left ventricular (LV) cavity, or into the ischemic zone in the anterior ventricular free wall. Measurements and Main Results:Echocardiographically measured myocardial function, including ejection fraction and fractional shortening, was quantitated 2 wks and 4 wks after administering MSCs or phosphate buffer solution. Hemodynamics, including cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure were measured 4 wks after administering MSCs or phosphate buffer solution. MSCs were counted in 5-&mgr;m sections obtained with cryostat from each harvested heart. Significant improvements in ejection fraction, fractional shortening, cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure followed injection of MSCs, regardless of the site of injection. However, the number of MSCs counted in the heart sections was significantly greater after direct myocardial injection. Conclusions:Independently of the site of injection and regardless of the different concentration of bone marrow mesenchymal stem cells identified in the myocardium, myocardial function was comparably improved in all groups of animals treated with MSCs.

Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia: contribution of TNF-α-induced protein 6

Aim:To investigate the effects of mesenchymal stem cells (MSCs) transplantation on rat global cerebral ischemia and the underlying mechanisms.Methods:Adult male SD rats underwent asphxial cardiac arrest to induce global cerebral ischemia, then received intravenous injection of 5×106 cultured MSCs of SD rats at 2 h after resuscitation. In another group of cardiac arrest rats, tumor necrosis factor-α-induced protein 6 (TSG-6, 6 μg) was injected into the right lateral ventricle. Functional outcome was assessed at 1, 3, and 7 d after resuscitation. Donor MSCs in the brains were detected at 3 d after resuscitation. The level of serum S-100B and proinflammatory cytokines in cerebral cortex were assayed using ELISA. The expression of TSG-6 and proinflammatory cytokines in cerebral cortex was assayed using RT-PCR. Western blot was performed to determine the levels of TSG-6 and neutrophil elastase in cerebral cortex.Results:MSCs transplantation significantly reduced serum S-100B level, and improved neurological function after global cerebral ischemia compared to the PBS-treated group. The MSCs injected migrated into the ischemic brains, and were observed mainly in the cerebral cortex. Furthermore, MSCs transplantation significantly increased the expression of TSG-6, and reduced the expression of neutrophil elastase and proinflammatory cytokines in the cerebral cortex. Intracerebroventricular injection of TSG-6 reproduced the beneficial effects of MSCs transplantation in rats with global cerebral ischemia.Conclusion:MSCs transplantation improves functional recovery and reduces inflammatory responses in rats with global cerebral ischemia, maybe via upregulation of TSG-6 expression.

Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats

We hypothesized that administration of allogeneic bone marrow mesenchymal stem cells (MSCs) by intravenous, intraventricular or intramyocardial injection could improve myocardial function after survival time after cardiopulmonary resuscitation in myocardial infarcted rats. Myocardial infarction was induced by ligation of the left anterior descending artery in 54 rats (6 groups, 9 rats for each group). Left ventricular remodeling was quantitated weekly by ejection fraction (EF) measurement. One month after ligation, animals were randomized to receive injection of either MSCs 5x10(6) labeled with PKH26 in phosphate buffer solution (PBS) or PBS alone as a placebo. MSCs or PBS were administered by injection into the right femoral vein, the left ventricular cavity, or into the infracted anterior ventricular free wall. Four weeks after MSC or PBS injection, ventricular fibrillation (VF) was induced and untreated for 6 min, followed by 6 min of CPR prior to defibrillation. Hemodynamics, including cardiac index (CI), left ventricular dP/dt40 (dP/dt40), left ventricular negative dP/dt (-dP/dt) and left ventricular diastolic pressure (LVDP) were measured at baseline and hourly following return of spontaneous circulation (ROSC). Labeled MSCs were observed in 5 microm sections obtained with a cryostat from each harvested heart. Independently of the site of injection of MSCs, EF, CI, dP/dt40, -dP/dt, and LVDP were significantly improved and sustained before and after CPR in the animals treated with MSCs and were associated with significantly increased survival time when compared with the corresponding PBS treated animals.

Mechanism by which activation of δ-opioid receptor reduces the severity of postresuscitation myocardial dysfunction

Objective:Postresuscitation myocardial dysfunction has been recognized as a leading cause of early death after initially successful cardiopulmonary resuscitation. We have previously demonstrated that opening adenosine triphosphate (ATP)-sensitive K+ (KATP) channels or activation of &dgr;-opioid receptors minimized the severity of postresuscitation myocardial dysfunction and increased the duration of postresuscitation survival. In the present study, we investigated the potential mechanism of myocardial protection following &dgr;-opioid receptor activation in a rat model of cardiac arrest and cardiopulmonary resuscitation. Design:Randomized prospective animal study. Setting:Animal research laboratory. Subjects:Male Sprague-Dawley rats. Interventions:Ventricular fibrillation was induced in 24 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 mins of untreated ventricular fibrillation. Defibrillation was attempted after 6 mins of cardiopulmonary resuscitation. The animals were randomized to four groups: a) pentazocine (0.3 mg/kg), a &dgr;-opioid receptor agonist; b) pentazocine pretreated with KATP channel blocker, glibenclamide (0.3 mg/kg), administered 45 mins before induction of ventricular fibrillation; c) glibenclamide pretreated alone 45 mins before induction of ventricular fibrillation; and d) placebo. Pentazocine or saline placebo was injected into the right atrium after 5 mins of untreated ventricular fibrillation. Measurements and Main Results:Postresuscitation myocardial function, as measured by the rate of left ventricular pressure increase at 40 mm Hg, left ventricular end-diastolic pressure, and cardiac index, was significantly improved in pentazocine-treated animals. This was associated with significantly prolonged duration of survival. Except for ease of defibrillation, the beneficial effects of pentazocine were abolished by pretreatment with the KATP channel blocker glibenclamide. Conclusions:The postresuscitation myocardial protective effects provided by activation of &dgr;-opioid receptor may be mediated via opening KATP channels.

Transthoracic impedance for the monitoring of quality of manual chest compression during cardiopulmonary resuscitation

OBJECTIVE The quality of cardiopulmonary resuscitation (CPR), especially adequate compression depth, is associated with return of spontaneous circulation (ROSC) and is therefore recommended to be measured routinely. In the current study, we investigated the relationship between changes of transthoracic impedance (TTI) measured through the defibrillation electrodes, chest compression depth and coronary perfusion pressure (CPP) in a porcine model of cardiac arrest. METHODS In 14 male pigs weighing between 28 and 34 kg, ventricular fibrillation (VF) was electrically induced and untreated for 6 min. Animals were randomized to either optimal or suboptimal chest compression group. Optimal depth of manual compression in 7 pigs was defined as a decrease of 25% (50 mm) in anterior posterior diameter of the chest, while suboptimal compression was defined as 70% of the optimal depth (35 mm). After 2 min of chest compression, defibrillation was attempted with a 120-J rectilinear biphasic shock. RESULTS There were no differences in baseline measurements between groups. All animals had ROSC after optimal compressions; this contrasted with suboptimal compressions, after which only 2 of the animals had ROSC (100% vs. 28.57%, p=0.021). The correlation coefficient was 0.89 between TTI amplitude and compression depth (p<0.001), 0.83 between TTI amplitude and CPP (p<0.001). CONCLUSION Amplitude change of TTI was correlated with compression depth and CPP in this porcine model of cardiac arrest. The TTI measured from defibrillator electrodes, therefore has the potential to serve as an indicator to monitor the quality of chest compression and estimate CPP during CPR.

Expression of aberrant β-catenin and impaired p63 in craniopharyngiomas

Craniopharyngiomas are rare, histologically benign, non-neuroepithelial epithelial tumors arising from the sellar region, the molecular pathogenesis of CPs is yet not understood. The aim of the present study was to assess expression of aberrant β-catenin and impaired p63 in 66 craniopharyngiomas included 51 adamantinomatous craniopharyngiomas and 15 squamous papillary craniopharyngiomas. On immunohistochemistry, 47out of 51 adamantinomatous craniopharyngiomas, but not squamous papillary craniopharyngiomas, showed strong nuclear/cytoplasmic expression for β-catenin predominantly in compactly cohesive epithelial cells within the whorl-like arrays where ki-67 was almost absent and rarely in palisaded cells where ki-67 was mainly present. P63 overexpression was observed in 45 out of 51 adamantinomatous craniopharyngiomas and 14 out of 15 squamous papillary craniopharyngiomas. P63 stained not only in the nuclei of basal layer cells but also within the whorl-like arrays in adamantinomatous craniopharyngiomas and uniformly in squamous papillary craniopharyngiomas. Using quantitative real time polymerase chain reaction techniques to correlate p63 protein expression with p63 mRNA levels, TAp63 isoforms mRNA was reduced, whereas ▵Np63 mRNA elevated at levels in 5 snap frozen tissue samples with multiple large p63 positive cell clusters compared with normal tissues. In conclusion, the present study confirmed that the two variants of CPs have genetically not only distinctive but also common feature. It demonstrated that cytoplasm/nuclear β-catenin accumulation is an exclusively characteristic morphology of adaCPs. P63 immunohistochemical overexpression were found in both adaCPs and spCPs variant when analyzed in the same study. Taken together, the impaired p63 expression may be attributed to elevated ▵Np63 mRNA and reduced TAp63mRNA in CPs.

Inhibition of Drp1 by Mdivi-1 attenuates cerebral ischemic injury via inhibition of the mitochondria-dependent apoptotic pathway after cardiac arrest.

Mitochondrial fission is predominantly controlled by the activity of dynamin-related protein1 (Drp1), which has been reported to be involved in mitochondria apoptosis pathways. However, the role of Drp1 in a rat model of cardiac arrest remains unknown. In this study, we found that activation of Drp1 in the mitochondria was increased after cardiac arrest and inhibition of Drp1 by 1.2 mg/kg of mitochondrial division inhibitor-1 (Mdivi-1) administration after the restoration of spontaneous circulation (ROSC) significantly protected against cerebral ischemic injury, shown by the increased 72-h survival rate and improved neurological function. Moreover, the increase of the vital neuron and the reduction of cytochrome c (CytC) release, apoptosis-inducing factor (AIF) translocation and caspase-3 activation in the brain indicate that this protection might result from the suppression of neuron apoptosis. Altogether, these results indicated that Drp1 is activated after cardiac arrest and the inhibition of Drp1 is protective against cerebral ischemic injury in a rat of cardiac arrest model via inhibition of the mitochondrial apoptosis pathway.

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.

Even Four Minutes of Poor Quality of CPR Compromises Outcome in a Porcine Model of Prolonged Cardiac Arrest

Objective. Untrained bystanders usually delivered suboptimal chest compression to victims who suffered from cardiac arrest in out-of-hospital settings. We therefore investigated the hemodynamics and resuscitation outcome of initial suboptimal quality of chest compressions compared to the optimal ones in a porcine model of cardiac arrest. Methods. Fourteen Yorkshire pigs weighted 30 ± 2 kg were randomized into good and poor cardiopulmonary resuscitation (CPR) groups. Ventricular fibrillation was electrically induced and untreated for 6 mins. In good CPR group, animals received high quality manual chest compressions according to the Guidelines (25% of animals anterior-posterior thoracic diameter) during first two minutes of CPR compared with poor (70% of the optimal depth) compressions. After that, a 120-J biphasic shock was delivered. If the animal did not acquire return of spontaneous circulation, another 2 mins of CPR and shock followed. Four minutes later, both groups received optimal CPR until total 10 mins of CPR has been finished. Results. All seven animals in good CPR group were resuscitated compared with only two in poor CPR group (P < 0.05). The delayed optimal compressions which followed 4 mins of suboptimal compressions failed to increase the lower coronary perfusion pressure of five non-survival animals in poor CPR group. Conclusions. In a porcine model of prolonged cardiac arrest, even four minutes of initial poor quality of CPR compromises the hemodynamics and survival outcome.