New hemoglobin derivative aimed for improvement of oxygen metabolism in severe sepsis

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We have made S-Nitrosylated Polyethylene Glycol-conjugated Hemoglobin Derivative (SNO-Hb) which can donate nitric oxide (NO) as well as deliver the oxygen and have found this derivative is useful for the treatment of hemorrhagic shock in rat model. In this study, we are going to make new hemoglobin derivatiye useful in sepsis where plenty of NO exists and impaires oxygen uptake in the peripheral tissue.Cecum ligation puncture (CLP, ligated coecum was puctured twice by 18G needle) was performed in 250〜300g weighed Spraugue-Dowley rats3, making sepsis model (peritonitis). In control rats (n=7),anesthesia only (n=5),laparotomy only (n=5),and CLP (n=6),body temparature was 37.4±0.2℃,36.3±0.5,36.7±0.8,33.6±1.1,respectively, Also, blood pressure was 128±4 mmHg,120±4,129±7,105±6,respectively, heart rate was 515±7/min,466±14, 508±25,400±35,respectively, and CO2 production (1-2 hours post each procesure) was 2.25±0.15g/BWkg/hour, 2.06±00.12,2.06±0.10,1.43±0.18,respectiveiy. In CLP rats, metabolic rate was decreased and not in hyperdymanic circulatory state but in hypodymanic state.We could successfully measured stable metabolic rate in septic rats by the modified metabolic cage for CO2 production.We are going to make hyperdymanic circulatory state rat model by changing the size of puncture hole smaller in the ligated coecum.