Nanobubble oxygenation in cardiac arrest and acute vital organ ischemia

Abstract Direct intravenous delivery of gasses has been always considered an absolute contraindication due to the fear of air embolism. However, if it were made possible, direct intravenous high content oxygen solutions could ameliorate injury, improve tissue hypoxia and buy time for definitive interventions and/or prevent invasive interventions such intubations. The basic resting minute oxygen requirements of a human are 3ml/kg/min or 200- 300 ml of O2/min. During CPR, blood flow is significantly decreased and oxygenation at the lungs is frequently severely impaired. Both those conditions lead to vital organ and whole-body hypoxia. An effort to increase the overall oxygen content of circulating blood could have significant effect on end-organ oxygenation even with lower blood flow and could significant delay irreversible injury that leads to significant morbidity and eventually mortality in this patient population. We have developed a method with which a highly pressured mixture of saline and oxygen can be delivered directly into the vein at 1 Atm in order to dramatically increase the circulating oxygen blood content. We utilize high pressures (50-100 Atm) at room temperature (25-28C) to dissolve large volumes of oxygen in the infusate to make a clinically relevant therapy and sustain body oxygen requirements for up to 10- 20 min/L of saline infused. The concept is based on the simple idea that when the highly pressurized solution (eg. at 50 atm and 25C the dissolved volume of O2 /saline is ~2.5/1) is released under constant pressure through a nozzle that controls bubble nucleation rate and bubble size distribution evolution, a “mist” consisting of nucleated nanobubbles and saline water molecules can be delivered, which can be directly mixed with the returning venous blood. The presence of venous, unsaturated hemoglobin acts as an absorption sink for the delivered O2nanobubble solution (O2NBS). An optimal rate of mixing can be safe and minimize bubble formations through the process of immediate O2 uptake. Residual nanobubbles do not coalesce and therefore could circulate uninterrupted through the circulatory system to act as an additional oxygen reservoir. In Aim 1 we will study the physics and engineering methods to optimize the solution and nanobubble size characteristics under different upstream Pr/nozzle conditions. We aim to minimize nanobubble average size to safely deliver it in saline at 1atm and 37C. Aims 2 and 3 will assess the effect of the intravenous oxygen solution on blood and tissue oxygenation in animal models of simulated cardiac arrest and during prolonged CPR. Finally, a large 72 -hour survival study will be performed. The implications to public health are self-evident and far-reaching for diseases like cardiac arrest, hypoxic respiratory failure, emergencies requiring intubation and anesthesia.