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

ABSTRACT

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 minutes of untreated ventricular fibrillation (VF) followed by 6 minutes of CPR. Five minutes after resuscitation, 4.8 mg/kg of Art was intravenously administered for 2 hours in the CA/CPR + Art group. Intestinal fatty acid-binding protein (iFABP) and diamine oxidase (DAO) concentrations were compared among the three groups before CA and at 1, 2, 4, and 24 hours after resuscitation. At 24 hours post-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 7 and 6 swine in the CA/CPR and CA/CPR + Art groups, respectively. Serum iFABP and DAO 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 post-resuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.