EFFECT OF ARTESUNATE TREATMENT ON INTESTINAL INJURY AFTER CARDIOPULMONARY RESUSCITATION IN SWINE

Introduction: Intestinal injury is often caused by systemic ischemia-reperfusion injury early after cardiac arrest (CA) and resuscitation. Artesunate (Art) has been confirmed to protect vital organs against diverse of regional I/R injury. This study aimed to investigate the effect of Art on intestinal injury after CA and cardiopulmonary resuscitation (CPR) in swine. Methods: Twenty-two swine were randomly divided into three groups: sham (n = 6), CA/CPR (n = 8), and CA/CPR + Art (n = 8). The CA/CPR swine model was established by inducing 9 min of untreated ventricular fibrillation (VF) followed by 6 min of CPR. Five minutes after resuscitation, 4.8 mg/kg of Art was intravenously administered for 2 h in the CA/CPR + Art group. Intestinal fatty acid-binding protein and diamine oxidase concentrations were compared among the three groups before CA and at 1, 2, 4, and 24 h after resuscitation. At 24 h after resuscitation, intestinal zonula occluden-1 (ZO-1), occludin, apoptosis, caspase-3/gasdermin E (GSDME)-mediated pyroptosis proteins concentrations, and proinflammatory cytokine concentrations were examined to evaluate intestinal injury. Results: During CPR, spontaneous circulation was achieved in seven and six swine in the CA/CPR and CA/CPR + Art groups, respectively. Serum intestinal fatty acid-binding protein and diamine oxidase concentrations were significantly higher and intestinal tissue ZO-1 and occludin concentrations were significantly lower in the CA/CPR and CA/CPR + Art groups than in the sham group. However, Art treatment resulted in markedly improved levels of intestinal injury biomarkers compared with those in the CA/CPR group. Additionally, intestinal apoptosis and concentrations of caspase-3/GSDME-mediated pyroptosis proteins and proinflammatory cytokines were significantly higher in the CA/CPR and CA/CPR + Art groups than in the sham group. However, these variables were significantly lower in the CA/CPR + Art group than in the CA/CPR group. Conclusions: Art treatment effectively alleviates postresuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.