The Study Of The Protective Effect And Its Mechanism Of Edaravone On Organ Functions In Oral Fluid Resuscitation Of 50% Tbsa Full-thickness Burn In Dogs

Objective: The present study was performed to investigate whether edaravone inhibit free radical production and tissue edema, alleviate ischemia- reperfusion injury, and improve organ functions and survival rates in oral resuscitation of burn shock in dogs with 50% TBSA full-thickness burn injury.Methods: Thirty-two male Beagle dogs(11±0.5kg) were surgically prepared for measurements of hemodynamic parameters and intestinal mucosa blood flow(IMBF). 24 hours later the animals were subjected to 50% total body surface area(TBSA) full-thickness flame injury under 10～15 minutes of anesthesia by IV injection of propofol at 0.5ml/kg. Animals were randomly divided into two groups(each n=16): oral resuscitation group (gastric infusion of Glucose-electrolyte solution(GES), OR group) and edaravone group (gastric infusion of GES with edaravone, ED group). Dogs were given edaravone 2.5ml/kg intravenously in ED group at 0.5h and 8h post injury respectively. In the first 24-hours post injury, GES were intragastrically given to the animals in each group. Delivery rate and volume of GES were calculated according to Parkland formula. Delayed intravenous fluid resuscitation was performed at 24h post injury. Haemodynamic Parameters (MAP, CO, SVR, dp/dtmax) were determined with PICCO before and at 2h, 4h, 8h, 24h, 48h, 72h after injury under no anaesthesia state. Plasma Volume(PV) were detected by ICG method and IMBF determined by laser Doppler flowmetry. At the same time, bloods were collected for tests of pH, HCT, lactate, electrolyte and plasma osmotic pressure(POP). Plasma contents of alanine aminotransferase(ALT), creatinine(Cr), MB isoenzyme of creatine kinase(CK-MB) and TNF-αwere also detected. Urinary output and survival rates of 72h post injury were recorded. Six animals in each group at 8 hours, and those still survival at the end of 72 hours post injury were sacrificed. Tissues of heart, lung, liver, kidney and jejunum were harvested for evaluation of nitric oxide synthase(NOS), xanthine oxidase (XOD), malondialdehyde(MDA) and determination of water contents by oven drying method.Results: MAP and CO in both groups lowered quickly after burn; MAP of ED group showed no significant differences compared to that of OR group(P>0.05), while value of CO in ED group elevated compared to that in OR group from 4h postburn(P<0.05). SVR in OR and ED groups, which rose quickly after burn, showed no significant differences from each other(P>0.05). In both groups, dp/dtmax declined quickly after burn, while showed no differences from each other(P>0.05). IMBF in two groups lowered after burn. IMBF in ED group were markedly higher than those in OR group from 4h postburn(P<0.05). In two groups, PV values declined immediately after burn and rebounded to normal at 72h postburn, while showed no differences from each other(P>0.05). Urinary output volume of ED group was higher than that of OR group in the first 24hs post injury(P<0.05). Na+, POP and pH in two groups slided down after burn, which in ED group were markedly higher than those in OR group from 2h postburn(P<0.05). LAC, ALT and Cr in both groups rose, which in ED group were apparently lower than those in OR group(P<0.05). In both groups, CK-MB and HCT rose quickly after burn, while showed no differences from each other(P>0.05). Plasma contents of TNF-α, tissue contents of NOS, XOD, MDA and water contents of crucial organs were lower in ED group than those in only OR group(P<0.05).Conclusion: A dog model was successfully established to investigate the effect and its mechanism of edaravone on haemodynamic, organ functions and survival rates in oral fluid resuscitation of 50% TBSA full-thickness burn injury. The present results indicated that edaravone could efficiently alleviate the edema and improve perfusion of crucial organs in 50% TBSA burn injury. Possible mechanism of edaravone was potentially relevant with clear of free radical actions, inhibition of lipid peroxidation and relieve of ischemia reperfusion injury of crucial organs and tissues in early oral resuscitation of burns.