Creating Oxygen Therapeutics

A continuous supply of oxygen gas is required to maintain cellular structure and function. Even brief deficits in oxygenation, as occurs in patients with lung injury or airway problems, can cause the heart to stop beating, a disorder known as cardiac arrest. More than 200,000 patients per year in the US suffer from cardiac arrest in the hospital setting (i.e. in–‐ hospital cardiac arrest, IHCA). Among those, approximately ~40–‐60% are thought to be precipitated by hypoxia (i.e. asphyxia cardiac arrest, or ACA), with a mortality rate between 70 and 95%, and neurologic injury is common in survivors. In these patients, the rapid restoration of oxygen delivery to the brain, heart, and other vital organs is paramount to intact survival. Delays of a few minutes can be the difference between recovering back to health and permanent neurologic impairment. In the most critically ill patients, underlying lung disease (for example) makes restoration of normal oxygen levels difficult. To address this problem, we have developed a way to administer oxygen gas intravenously. We created ultra–‐stable and pH–‐triggered self–‐ eliminating microbubbles as oxygen carriers. These microbubbles are stable for years, and rapidly dissolve when infused into blood. Repeated i.v. infusions were safe and hemodynamically well tolerated in rodents. When added to a standard resuscitation algorithm in an asphyxia cardiac arrest model, microbubbles increased survival from 0% to 100%. I.V. oxygen using functional microbubbles may serve as a useful adjunct to current cardiac arrest therapy and other hypoxic conditions.

Dr. Brian D. Polizzotti is an Assistant Professor of Pediatrics at Harvard Medical School. His laboratory specializes in the rational design of nanoparticles for oxygen delivery.  As a researcher in the Translational Research Program (TRP) at Boston Children’s Hospital, Dr Polizzotti is actively involved in the development of non-clinical and human clinical trials that seek to improve the care of children, and to ensure adequate infrastructure to support non-clinical and clinical translational research projects.  His recent work in Science Translational Medicine, for example, has shown that the optimal window of time to stimulate heart muscle cell regeneration (cardiomyocyte proliferation) in humans is the first six months of life and that that early administration of neuregulin may provide a targeted and multipronged approach to prevent heart failure in infants with CHD.