Abstract
Background Post-resuscitation syndrome, involves a severe inflammatory response following successful cardiopulmonary resuscitation. The potential mechanism of Vitamin C (VitC) after cardiopulmonary resuscitation on myocardial and cerebral function, duration of survival is undefined. Methods and Results A first set of experiments were done in 18 male Sprague-Dawley rats for the investigation of short-term follow-up, randomized into 3 groups: (1) sham; (2) controls; (3) VitC. Ventricular fibrillation was electrically induced and untreated for 6 minutes. Cardiopulmonary resuscitation including chest compression and mechanical ventilation were then initiated and continued for 8 minutes followed by defibrillation. At 5 minutes after return of spontaneous circulation, either VitC (200 mg/kg) or placebo was administered by intravenous infusion with a syringe pump for half an hour. There were significant improvements in myocardial function and buccal microcirculation in rats treated with VitC after return of spontaneous circulation 4 hours compared with controls. VitC inhibited proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), SDC-1 (Syndecan-1), and hyaluronic acid in plasma compared with controls (P<0.01). VitC decreased reactive oxygen species production and inhibited p38/MAPK (mitogen-activated protein kinase) pathway phosphorylation. A second set with 20 animals was used for assessing the neurological deficit score after return of spontaneous circulation 72 hours, randomized into 2 groups: 1) controls; 2) VitC. The survival rate and neurological deficit score after return of spontaneous circulation 72 hours were improved in VitC-treated animals compared with those of the control group. Conclusions VitC reduces the severity of post-resuscitation myocardial and cerebral dysfunction and improves the survival. The mechanisms may involve inhibiting transcription of inflammatory cytokines and oxidative stress, thus protecting the integrity of the vascular endothelium. Meanwhile VitC reduces shedding of SDC-1 and alters p38/MAPK phosphorylation and microcirculation.