BioEd Online

An injection of oxygen-filled microcapsules into the bloodstream has kept rabbits alive for up to 15 minutes without taking a single breath.

Oxygenating the blood by bypassing the lungs in this way could be lifesaving for patients with impaired breathing or obstructed airways, says John Kheir at the Department of Cardiology at Boston Children’s Hospital, who led the research, published today in Science Translational Medicine¹.

What’s more, besides potentially preventing cardiac arrest and brain injury induced by oxygen deprivation, boosting oxygen levels in the bloodstream could also prevent cerebral palsy by injecting fetuses whose blood supply has been compromised.

The microcapsules consist of a single layer of lipids each surrounding a tiny pocket of oxygen gas. In the past efforts have been made to inject free oxygen gas directly into the bloodstream to treat hypoxemia or other low oxygen related conditions, such as cyanosis, with varying degrees of success, says Kheir.

John Harvey Kellogg, for example, experimented with oxygen enemas, an idea that has been picked up relatively recently in the form of bowel infusers², says Mervyn Singer, professor of intensive care medicine at University College Hospital, in London.

But these methods can be dangerous because there is a risk of the free oxygen gas accumulating into larger bubbles that can form potentially lethal blockages, or pulmonary embolisms.

Injecting oxygen in liquid form would avoid this but is even less practical since the low temperature of liquid oxygen would also be harmful. The microcapsules, however, get the best of both worlds: delivering the oxygen in gas form but encapsulated and suspended within an emulsion that can be injected through an intravenous infusion.

Once in the bloodstream the microcapsules mingle with red blood cells as they circulate, with the oxygen diffusing into the cells on contact. This happens within seconds, says Kheir. “By the time they get to the lungs the vast majority of the oxygen has been transferred to the red blood cells,” he says. This distinguishes these microcapsules from the various form of artificial blood now used, which can carry oxygen but still need to lungs to receive it. The lipid foam is also safe, says Kheir. “As the oxygen leaves them, the shell buckles and folds, with the lipids breaking off,” he says. The body then reabsorbs them.

In the experiment, rabbits whose airways had been completely blocked could survive up to 15 minutes without breathing, with normal blood pressure and heart rate, and showed no indication of liver damage caused by oxygen deprivation, nor of any heart or lung damage or pulmonary embolisms.

The microcapsules are also easy and cheap to make, says Kheir. They effectively self-assemble and are formed by exposing the phospholipid components to intense sound waves in a purely oxygenated environment, a process known as sonication.

It’s a very sophisticated approach, says Singer. Heart and lung machines can also oxygenate the blood, as can extracorporeal membrane oxygenation (ECMO), he says. However these are more suited to longer-term life support and would not be much use in acute cases, such as when someone’s trachea was blocked, he says.

Indeed one of the great advantages of this approach is the speed at which it works, says Kheir. However, although Kheir believes it may be possible to extend the 15 minutes to as much as 30 minutes he doubts it could be pushed much further because there are limits on how much additional fluid can be pumped into the bloodstream. “It’s not going to replace the lungs, it just replaces their function for a limited period of time.”