Development of a Minimal-Bulk Oxygen Delivery Product to Enhance Survival During Hemorrhagic Shock/Studies Regarding the Use of Perfluorocarbon- Derived Intravascular Microbubbles from Oxygen Transport

摘要

Production of microbubble forming dodecafluoropentane emulsion (DDFPe); NuvOx Pharma LLC, Tucson, AZ was able to make high-quality emulsions February 2008, which have been successfully used in resuscitation of rats (sever hemodilution) and pigs (potentially lethal hemorrhagic shock) over the last 16 months. Goal 2: A shock model combining hemorrhage (32 mL/kg total blood loss) and a fractured femur bone was developed in pentobarbital anesthetized pigs weighing approximately 25 kg. In 19 pigs not given any treatment, approximately 30% of the pigs survived for six hours. Goal 3: Comparison of Hextend (plasma expander) and DDFPe (blood substitute) for low volume resuscitation in the model developed during Goal 2. Eight out of ten pigs survived if Hextend was given 45 minutes after bleeding, suggesting a survival of approximately 80%. All six pigs given 0.6 mL/kg DDFPe (NuvOx Pharma LLC) survived with good physiological values for more than six hours. This was interpreted as 100% of the DDFPe treated pigs survived for the required time. Repeatedly observed in Hextend treated pigs was development of severe pulmonary distress with foam in the lungs, dyspnea, and gradually rising content of CO2 and falling O2 tension in arterial blood. Goal 4: Semi-conscious pigs were bled31.5 mL/kg over 26 min and were allowed to develop shock over the next approximately 35 min. Two randomly selected groups (n=6 each) were resuscitated with either 7 mL/kg Hextend or 0.6 mL/kg DDFPe over 30 min. One pig died before any treatment was given. All treated pigs survived the experiments for 11 to 14 days, then euthanized. One of the Hextend treated pigs suffered severe sequel from the shock with no weight gain and was required euthanization on the 11th day. All DDFPe treated pigs were in good condition, increasing their weight at a normal rate.