Abstract
Following cardiopulmonary resuscitation (CPR), the ensuing cardiac and cerebral injuries contribute to the poor outcome of cardiac arrest (CA) victims, in which the pathogenetic process is possibly driven by cell pyroptosis and ferroptosis. Mesenchymal stem cells (MSCs) have been shown to be a promising strategy for post-resuscitation cardiac and cerebral protection in rat, but its effectiveness in the clinically relevant swine model and the potential protective mechanism remain unknown. The present study was designed to investigate whether MSCs administration could alleviate post-resuscitation cardiac and cerebral injuries through the inhibition of cell pyroptosis and ferroptosis in swine. Twenty-four male domestic swine were randomly divided into three groups: sham, CPR, and MSC. A dose of 2.5×106/kg of MSCs derived from human embryonic stem cells was intravenously infused at 1.5, and 3 days prior to CA. The animal model was established by 8 min of CA and then 8 min of CPR. After resuscitation, cardiac, cerebral function and injury biomarkers were regularly evaluated for a total of 24 h. At 24 h post-resuscitation, pyroptosis-related proteins (NLRP3, ASC, cleaved caspase-1, GSDMD), proinflammatory cytokines (IL-1β, IL-18), ferroptosis-related proteins (ACSL4, GPX4) and iron deposition in the heart, cortex and hippocampus were measured. Consequently, significantly greater cardiac, cerebral dysfunction and injuries after resuscitation were observed in the CPR and MSC groups compared with the sham group. However, the severity of cardiac and cerebral damage were significantly milder in the MSC group than in the CPR group. In addition, the expression levels of NLRP3, ASC, cleaved caspase-1, GSDMD and ACSL4, the contents of IL-1β and IL-18, and the level of iron deposition were significantly higher while the expression level of GPX4 was significantly lower in the heart, cortex and hippocampus in all resuscitated animals compared with the sham group. Nevertheless, MSCs administration significantly decreased post-resuscitation cardiac, cerebral pyroptosis and ferroptosis compared to the CPR group. Our results showed that the administration of MSCs significantly alleviated post-resuscitation cardiac and cerebral injuries in swine, in which the protective effects were related to the inhibition of cell pyroptosis and ferroptosis.
Highlights
After obtaining successful cardiopulmonary resuscitation (CPR) from cardiac arrest (CA) events, most patients will die of postresuscitation cardiac and cerebral injuries in the following hospitalization (Laver et al, 2004; Neumar et al, 2008)
During post-resuscitation observation, HR was higher and mean arterial pressure (MAP) was lower in all resuscitated animals compared with the sham group; a slower increase in HR was observed in the Mesenchymal stem cells (MSCs) group than in the CPR group, in which the differences were significant starting 2 h after resuscitation between the two groups
Postresuscitation pH was lower and lactate was higher in all resuscitated animals compared to the sham group; a faster improvement in them was observed in the MSC group, in which the value of lactate at 4 h post-resuscitation was significant lower than that in the CPR group
Summary
After obtaining successful cardiopulmonary resuscitation (CPR) from cardiac arrest (CA) events, most patients will die of postresuscitation cardiac and cerebral injuries in the following hospitalization (Laver et al, 2004; Neumar et al, 2008). Cardiac and cerebral pathogenetic mechanism after resuscitation and their effective therapeutic target remain to be investigated (Burstein and Jentzer, 2020). Two studies demonstrated that MSCs pretreatment and posttreatment significantly improved postresuscitation cardiac and cerebral function in rats, respectively (Wang et al, 2008; Wang et al, 2009). Another one study demonstrated that the administration of MSCs significantly ameliorated post-resuscitation brain damage, and promoted its angiogenesis and neurological recovery through enhancing the expression of brain-derived neurotrophic factor and vascular endothelial growth factor in rats (Zhou et al, 2017). The effectiveness of MSCs administration in a clinically relevant, large-animal model of CA and resuscitation and its potential protective mechanism require further investigations
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
