Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Quality of Chest Compressions Differs over Time between Advanced and Basic Life Support

Purpose: According to guideline recommendations, chest compressions (CC) during cardiopulmonary resuscitation (CPR) should be performed at a rate of 100 - 120 per minute, with a CC fraction (CCF) of ≥80%. The aim of this work is to explore whether CC quality differs between advanced life support (ALS) and basic life support (BLS) performed by two rescuers. Method: Cardiopulmonary resuscitation was performed by two ambulance personnel in ten ALS and ten BLS manikin scenarios. Data from these scenarios were then compared with data on ten ALS cases from the clinical setting, all with non-shockable rhythms. Data from the first two 5-minute periods of CC were evaluated from impedance data (LIFEPAK 12 defibrillator monitors) using a modified Laerdal Skillmaster manikin. Quality parameters compared were: number of CC pauses (CCPs), total time of CC (%), number of CC given and CC rate/min. Results: During the first 5 minutes, the BLS manikin scenarios had the highest number of CCPs, 15 (14 - 16), compared with the ALS manikin scenario, 14 (13 - 15), and the clinical ALS cases, 12 (10 - 15). The BLS scenario also had the highest CCFs, 81% (77% - 85%), and number of CC, 450 (435 - 495), compared with the ALS manikin scenario, 75% (64% - 81%) and 400 (365 - 444) respectively, and the clinical ALS cases, 63% (50% - 74%) and 408 (306 - 489). The median rate of CC/min in the BLS scenario was 115 (110 - 120) compared with the ALS manikin scenario, 110 (106 - 115), and the clinical ALS cases, 130 (118 - 146). During the second 5-minute period, the BLS scenario had the highest number of CCPs, 16 (15 - 17), compared with 15 (14 - 16) for the ALS manikin scenario and 11 (11 - 12) for the clinical ALS cases. The CCF in the BLS setting was 79% (75% - 83%), and the number of CC 455 (430 - 480), compared with the ALS manikin scenario, 79% (74% - 84%) and 435 (395 - 480) respectively, and the clinical ALS cases, 71% (57% - 77%) and 388 (321 - 469) respectively. The median CC rate was 118 (113 - 124) for BLS, 111 (105 - 120) for ALS manikins and 123 (103 - 128) CC/min for clinical ALS cases. Conclusion: None of the groups being studied could deliver CC at a rate of 100 - 120 CC/min or a CCF of ≥80% over the whole 10-minute period in any of the resuscitation scenarios analyzed. However, BLS had the best compliance with CC quality recommendations according to the 2010 guidelines.