Don’t hyperventilate

Don’t hyperventilate

Here’s another example of some interesting science that doesn’t need any hype. The news blurb is titled Injectable Oxygen Keeps People Alive Without Breathing and was shared here: http://goo.gl/xjmeE4 I promised Rahul Roy that I would follow up after reading the full journal article. Notice the title on the journal article is less sensational, Oxygen Gas–Filled Microparticles Provide Intravenous Oxygen Delivery JN Kheir et al. Sci Transl Med 27 June 2012 http://goo.gl/9tN6yx   Techandfacts.com actually did a decent job reporting the science. The title is a little hyped but not bad. I’ve certainly seen worse, e.g., Bench to Bedside http://goo.gl/xudsu

So what is this article about, what’s the science?

❤ Lipidic oxygen-containing microparticles (LOM)

Dr. Kheir et al created microbubbles or LOMs to deliver oxygen when patients have difficulty breathing. This is an important part; it is not a blood substitute. It is not intended for trauma involving blood loss. We’ll get back to that later. What is LOM? When you make a vinaigrette you notice that oil and water don’t mix. You can shake/whisk the mixture or use an emulsifier (like mustard) to make an emulsion (a mixture of two liquids that normally don’t mix). Micelles are formed when a molecule has a hydrophobic part (doesn’t like water) and a hydrophilic part (likes water) and it’s placed in a liquid. If the liquid is water, the hydrophobic parts try to escape the water and end up on the inside of a sphere with the hydrophilic part on the outside. So the lipidic part of LOM is used to make micelles with oxygen inside. They use sound waves (via a sonicator) to disrupt the micelles enough to trap the oxygen inside of them. A red blood cell is 7-8 µm in diameter and the LOMs are 2-4 µm so they have no problem getting through the capillaries.

❤ O2 delivery vs. O2 carrier

So why is this good for short term use when there may be an issue with breathing but not in a trauma, blood loss situation? The LOMs are injected into the bloodstream where they can quickly oxygenate the blood. See the beaker of blood before and after adding LOMs (via the journal article). As the oxygen leaves the LOMs and saturates the hemoglobin in blood, they shrink. Think of a balloon releasing oxygen. The “deflated” LOMs cannot be “re-inflated” in the bloodstream (remember the sonicator was needed to get the oxygen in). You can see a deflated LOM in the lower left of the cartoon. Also carbon dioxide is not removed. In the short term this isn’t an issue. If this were needed for longer use, the CO2 would build up and make the blood acidic.

So what’s the difference between O2 delivery and an O2 carrier? LOMs are an O2 delivery system. Oxygen (or carbon dioxide for that matter) does not go back to the LOMs as they circulate. There two types of artificial oxygen carriers: hemoglobin based and perfluorocarbon (PFC). The LOMs are closer to PFC formulations.

❤ Perfluorocarbon (PFC)

A perfluorocarbon is an organic compound made up of carbon and fluorine. Emulsions of PFCs can be made that carry oxygen. Early on the emulsifiers used in PFC emulsions caused allergic reactions in people. The biggest problem with PFCs in the context of artificial blood is that the oxygen carrying characteristics require high oxygen content in the blood in order to release the oxygen. If you look at the figure below (http://goo.gl/csOsnk) you can see that you need a higher partial pressure (pO2, oxygen concentration) for the PFC relative to blood to release oxygen. Here’s a video that shows a mouse breathing liquid PFC. You might see other videos incorrectly state that it is a mouse breathing water.

Part 1 Wonders of the Human Body – BBC Explorations | Storyteller Media

❤ 2,3 diphosphoglycerate (2,3 DPG)

So what makes blood or hemoglobin so much better than PFC for oxygen carrying? A little compound called 2,3 diphosphoglycerate (2,3 DPG) is the key. It’s an allosteric effector. Allos from Greek means other and stereos means space. So an allosteric effector changes the shape or folding of a protein when bound or unbound. When 2,3 DPG is bound it shifts hemoglobin to the low affinity state for oxygen, i.e., releasing it more readily. It’s increased levels help in conditions of low oxygen/blood, e.g. traumatic blood loss.

One other tidbit, these microbubbles aren’t new. They have been used as contrast agents for ultrasound imaging, which I’ll talk about in another post. I can also talk more about hemoglobin based oxygen carriers in a future post if there is interest.

Happy #ScienceSunday