The goal of this Phase 1 project is to develop the AS-O2-001 System for intravenous, gaseous oxygen microbubble delivery for treatment of hypoxia. Hypoxia is a catastrophic illness that can result from acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, COVID-19, congestive heart failure and myocardial infarction. Current treatment options for severely affected patients include extracorporeal membrane oxygenation (ECMO) and mechanical ventilation, which are both invasive, expensive, and have iatrogenic sequalae. Agitated Solutions Inc. is developing a novel, minimally invasive alternative: the AS-O2-001 system delivers gaseous oxygen microbubbles into the inferior vena cava to delay or prevent mechanical ventilation or ECMO. Gaseous oxygen delivery has historically resulted in emboli formation; however, improved technology today enables the delivery of microbubbles (<100 µm). Microbubbles have unique properties, including their shrinking collapse, accelerated diffusion of gases, and negatively charged surface that prevents coalescence into emboli. Supersaturated oxygen is one such therapy that utilizes microbubbles of oxygen and has seen success in acute treatments (e.g. myocardial infarctions), but cannot readily be applied for chronic illness such as hypoxia due to fluid overload. Other alternative treatments in development, such as chemically coated microbubbles orintravascular respiratory assist catheters, have seen adverse metabolic effects or cardiac intolerance that prevent their clinical adoption. The AS-O2-001 system is promising because it utilizes the safety and efficacy of microbubbles in supersaturated oxygen but removes the overburden of fluids which would be deleterious in severely ill patients with hypoxia. Furthermore, the AS-O2-001 system is applied in the inferior vena cava and takes lessons learned from intravascular respiratory assist catheters in order to prevent cardiac intolerance, including a small form factor, a small insertion size, and the use of biocompatible materials. In Aim 1, the AS-O2-001 System will be developed and tested in an in vitro model to characterize its safety in preventing formation of air emboli and its effectiveness in delivering a therapeutic relevant dose. In Aim 2, the System will be evaluated in vivo to demonstrate the safety and proof of concept of intravenous delivery of oxygen in a porcine model of normoxemia and hyperoxemia. Successful completion of this project will demonstrate the feasibility of this novel and innovative method of delivering therapeutic oxygen as intravenously injected microbubbles.
Public Health Relevance Statement: Project narrative: The AS-O2-001 System, a gaseous oxygen infusion pump intravenously placed in the femoral vein, would provide a clinical breakthrough for hypoxia treatment to delay or prevent ECMO or mechanical ventilation. Development of this system solves the main issue of intravascular blood oxygenation techniques today, namely, it (1) prevents the formation of dangerous emboli, (2) does not rely on infusion of fluid or chemical shells, and (3) safely and therapeutically delivers oxygen to hypoxic tissue. In this project, the AS-O2-001 System will be developed, tested grossly for safety and efficacy in a benchtop model of normoxia and hypoxia, and validated in a pig model. Ultimately, it will be useful to treat a wide range of conditions including acute respiratory distress syndrome, acute myocardial infarction and critical limb ischemia.
Project Terms: Hypoxemic Respiratory Failure, Hypoxic Respiratory Failure, Chronic Obstructive Pulmonary Disease, COPD, Chronic Obstruction Pulmonary Disease, Chronic Obstructive Lung Disease, ultrasound, absorption, Adoption, Affect, Air, Animals, Dysbarism, Barotrauma, Beak, Behavior, Biocompatible Materials, Biomaterials, biological material, Blood, Blood Reticuloendothelial System, Blood Circulation, Bloodstream, Circulation, Carbon Dioxide, CO2, Carbonic Anhydride, Cardiovascular system, Cardiovascular, Cardiovascular Body System, Cardiovascular Organ System, Heart Vascular, circulatory system, Catastrophic Illness, Cell Membrane Permeability, membrane permeability, Charge, China, Mainland China, Chronic Disease, Chronic Illness, chronic disorder, Critical Illness, Critically Ill, Dangerousness, Diffusion, Embolism, Embolus, Extracorporeal Membrane Oxygenation, Femoral vein, Future, Gases, Goals, Heart, Heart failure, cardiac failure, Congestive Heart Failure, Cardiac Failure Congestive, Heart Decompensation, chronic heart failure, hemodynamics, Hypercapnia, carbon dioxide retention, elevated carbon dioxide, hypercarbia, increased level Carbon dioxide, Infusion Pumps, Infusors, Perfusion Pumps, Lung, Lung Respiratory System, pulmonary, Metals, Methods, Myocardial Infarction, Cardiac infarction, Myocardial Infarct, cardiac infarct, coronary attack, coronary infarct, coronary infarction, heart attack, heart infarct, heart infarction, NO2, Nitrogen Peroxide, Nitrogen Dioxide, Nasal, Nasal Passages Nose, Respiratory System, Nose, Nasal Passages, Nose, O element, O2 element, Oxygen, Patients, pressure, Lung Tissue Fibrosis, fibrosis in the lung, lung fibrosis, Pulmonary Fibrosis, Ramp, ARDS, Acute Respiratory Distress, Adult ARDS, Adult RDS, Adult Respiratory Distress Syndrome, Da Nang Lung, Shock Lung, Stiff lung, wet lung, Acute Respiratory Distress Syndrome, Safety, Ovine, Ovis, Sheep, Septic Shock, Pigs, Suidae, Swine, porcine, suid, Family suidae, Technology, Testing, Tissues, Body Tissues, Translating, Inferior vena cava structure, Inferior Vena Cava, Measures, Catheters, Acute myocardial infarction, Acute myocardial infarct, hyperbaric chamber, hyperbaric O2 chamber, hyperbaric oxygen chamber, improved, Procedures, Continuous Positive Airway Pressure, CPAP, CPAP Ventilation, Mechanical ventilation, mechanical respiratory assist, mechanically ventilated, Peripheral, Surface, Acute, Clinical, Diffuse, Phase, Variant, Variation, Physiological, Physiologic, Chemicals, kidney function, Renal function, O2 toxicity, oxygen poisoning, oxygen toxicity, Hypoxic, Oxygen Deficiency, Hypoxia, Acute Pulmonary Injury, Acute Lung Injury, Sample Size, Lung damage, pulmonary damage, pulmonary injury, pulmonary tissue damage, pulmonary tissue injury, lung injury, Therapeutic, fluid, liquid, Liquid substance, Metabolic, Intravenous, Diagnostic, Knowledge, mechanical, Mechanics, Scientist, Hour, Continuous Infusion, Techniques, System, Cannulas, hypervolemia, Fluid overload, Cardiopulmonary, respiratory assistance, respiratory assist, Infusion, Infusion procedures, success, Practice Management, novel, Devices, hypoxemic, Hypoxemia, Bypass, Modeling, Property, Adverse effects, Ischemic Stroke, Microbubbles, Effectiveness, preventing, prevent, Alveolar, Dose, iatrogenic, iatrogenically, iatrogenicity, Iatrogenesis, Preclinical Models, Pre-Clinical Model, in vitro Model, in vivo, Myocardial, Cardiac, Development, developmental, preclinical study, pre-clinical study, cost, Treatment Efficacy, intervention efficacy, therapeutic efficacy, therapy efficacy, innovation, innovate, innovative, prototype, high risk, alternative treatment, FDA approved, minimally invasive, effective therapy, effective treatment, clinical practice, risk minimization, Systems Development, improved outcome, Injections, hemocompatibility, COVID-19, COVID19, CV-19, CV19, corona virus disease 2019, coronavirus disease 2019, coronavirus disease-19, coronavirus infectious disease-19, critical limb Ischemia, normoxia, porcine model, pig model, piglet model, swine model>
