Artesunate preserves post-resuscitation myocardial and neurologic function in a rat model of cardiac arrest and cardiopulmonary resuscitation.

Background: To investigate the effects of Artesunate (Art) on post-resuscitation myocardial and neurologic function, survival duration, and the underlying mechanisms in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Methods: Thirty healthy male Sprague-Dawley rats were randomly allocated into three groups: Sham, Control(CA/CPR + vehicle),and ART(CA/CPR + Art). The latter two groups were further divided into survival and non-survival subgroups. CA were induced via 6-minute ventricular fibrillation, followed by 8 min of CPR. After the return of spontaneous circulation (ROSC), rats in the respective groups received either a vehicle or Art injection at random. Electrocardiogram (ECG) and arterial pressure were continuously monitored. In non-survival subgroups (euthanized 4 h post-ROSC), serum and tissue samples were analyzed for inflammatory cytokine concentrations, oxidative stress indices, myocardial injury markers, phosphorylated p38 (pp38), and echocardiography was performed. In survival subgroups, neurological deficit scores (NDS) were assessed at 24, 48, and 72 h post-ROSC, along with monitoring the duration of survival. Results: Art reduced the severity of post-resuscitation myocardial dysfunction compared to control group. It attenuated interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cardiac troponin I (cTnI) plasma levels 4 h after ROSC. In comparison with the control group, Art treatment led to a marked decrease in Thiobarbituric acid reactive species (TBARS) and 4-hydroxy-2-nonenal(4-HNE) expression, accompanied by upregulation of superoxide dismutases (SOD) activity in both heart and brain tissues. Art administration also downregulated the phosphorylation of p38. Post-resuscitation neurologic function and duration of survival were improved significantly in Art treated animals. Conclusions: This study demonstrated that Art reduces the severity of post-resuscitation myocardial and neurologic dysfunction, improves survival duration in a rat model of CA. The underlying mechanism may be related to anti-inflammation, oxidative stress and may be associated with regulation of 4-HNE induced p38 Mitogen activated protein kinase (MAPK) pathway activation.