Effect of Alda-1 on ferroptosis in cardiomyocytes after cardiac arrest and cardiopulmonary resuscitation in swine / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of Alda-1 on ferroptosis in cardiomyocytes after cardiac arrest and cardiopulmonary resuscitation in swine.Methods:Twenty-two healthy male white swine, weighing 35-43 kg, were divided into 3 groups using a random number table method: sham operation group (group S, n=6), cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR, n=8) and Alda-1 group ( n=8). The animals only underwent the general preparation in group S, and the swine model of cardiac arrest and cardiopulmonary resuscitation was developed by 8 min of electrically induced cardiac arrest through the pacing catheter in the right ventricle followed by 8 min of cardiopulmonary resuscitation in CA-CPR and Alda-1 groups.Alda-1 0.88 mg/kg was intravenously injected at 5 min after resuscitation in group Alda-1, and the equal volume of vehicle was administered instead in the other two groups.Stroke volume (SV) and global ejection fraction (GEF) were measured using PiCCO before developing the model and at 1, 2 and 4 h after resuscitation (T 0-3). Venous blood samples were collected from the femoral vein to measure the concentrations of serum cardiac troponin (cTnI) by enzyme-linked immunosorbent assay at T 0-3, and at 24 h after resuscitation (T 4). The animals were then sacrificed, and myocardial tissues in the left ventricle were harvested to measure the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) (by Western blot), iron deposition (by Prussian blue staining), 4-hydroxy-2-nonenal (4-HNE) content (by enzyme-linked immunosorbent assay), and malondialdehyde (MDA) and glutathione (GSH) contents (by colorimetry). Results:Compared with group S, SV and GEF were significantly decreased at T 1-3, the serum concentrations of cTnI were increased at T 1-4, myocardial ACSL4 expression was up-regulated, GPX4 expression was down-regulated, iron deposition and contents of 4-HNE and MDA were increased, and the content of GSH was decreased in CA-CPR and Alda-1 groups ( P<0.05). Compared with group CA-CPR, SV and GEF were significantly increased at T 2-3, the serum concentrations of cTnI were decreased at T 3-4, myocardial ACSL4 expression was down-regulated, GPX4 expression was up-regulated, iron deposition and contents of 4-HNE and MDA were decreased, and the content of GSH was increased in group Alda-1 ( P<0.05). Conclusions:Alda-1 can alleviate myocardial injury after cardiac arrest and cardiopulmonary resuscitation in swine and further improve cardiac dysfunction, and the mechanism may be related to inhibition of cell ferroptosis.