We have identified ROX , a Reserve of Oxygen in blood, which is required by the body to generate the energy for proper functioning of muscles, nerves, and other needs.

THE ROX HYPOTHESIS

A special mechanism exists that uses white blood cells (WBCs) to encapsulate oxygen from red blood cells (RBCs) and transports it to all the cells in the body. For example, the volume of a large motor neuron is about 1,000 times the volume of a single RBC. For this neuron to fire, it requires a 30% increase in oxygen delivery to the mitochondria inside the neuron, within 1/1000th of a second. Oxygen is essentially not soluble in the water or plasma and cytosol. Simple diffusion of oxygen from the RBC, through the plasma and capillary walls, past other tissue, through the neuron wall, and into the mitochondria of the neuron is an unreasonable mechanism for four reasons: (1) huge amounts of oxygen delivery are required, (2) the delivery must be made within milliseconds, (3) the oxygen needs to be signaled when needed for firing, and (4) it cannot be diluted on the way to the neuron.

This means that each of us has a limited amount of ROX that can be tapped into. Healthy amounts of ROX deliver oxygen to the mitochondria inside our cells, and the oxygen is used properly and efficiently—where it is needed and when it is needed. But, when ROX is in disarray, it prematurely bursts before reaching the cell’s mitochondria and generates unwanted radical oxygen species and can cause neuronal damage (i.e., ALS). Plausibly, then, when stress causes ROX depletion, disease can happen.

WHAT IS ROX. WHAT IS KNOWN ABOUT ROX

To observe the behavior of ROX, consider the following experiments. A small sample of blood is placed in a closed cell and exposed to stress. Oxygen is measured as a function of time. In the two example runs shown below, the concentration of oxygen remains at essentially zero for hours after being stressed, and then suddenly and spontaneously goes way up, and then comes back down. Where does this oxygen suddenly come from? We define this oxygen peak as a reservoir of oxygen, or ROX, which suddenly and spontaneously breaks open to release its oxygen when it is stressed.

The run on the left shows the oxygen released when whole blood is stressed with mechanical shear (vigorous mixing), bacteria, and a chemical toxin. Note that at the start of the run, there is no oxygen in the hemoglobin of the red blood cells (RBCs), because the oxygen starts at zero concentration. The release of oxygen comes from ROX.

On the right is a run for white blood cells (WBCs), stressed with mechanical shear and chemical toxin. The oxygen released by the WBCs is 7,880 micrograms per ml of cells as compared to 650 for saturated RBCs. The difference is significant---ROX from WBCs can store at least ten times as much oxygen as RBCs.

After several hundred runs(^1-5), we have determined that these oxygen peaks from ROX happen more at higher levels of induced stress. Also, the higher the concentration of white blood cells, the more likely it becomes that spontaneous bursts of oxygen from ROX appear.

To summarize, blood contains reservoirs of oxygen, ROX, that are released when the blood is exposed to physical, chemical, or biological stress. ROX does not behave like hemoglobin, which is in equilibrium with oxygen partial pressure. In hemoglobin, when oxygen partial pressure is low, hemoglobin releases oxygen until equilibrium is observed. When oxygen partial pressure is high, hemoglobin absorbs oxygen. ROX does not release or absorb oxygen as a function of partial pressure.

Stress, not partial pressure causes the release of oxygen from ROX. This release can take place in the absence of red cells. The ROX oxygen is far more concentrated than red cell oxygen. ROX has been measured at 35,000 micrograms of oxygen per ml, as compared to 650 micrograms per ml for packed red cells. This is 54 times as much as RBCs can carry. It is impossible to pack that much oxygen into hemoglobin.

WHY HAS ROX NOT BEEN IDENTIFIED EARLIER?

Unlike hemoglobin, which has a well-defined equilibrium curve with the partial pressure of oxygen, and which attains that equilibrium relatively quickly, ROX can stay hidden for many hours, and will not break open unless exposed to a systematic stress.

ROX ANALYZER

We have developed the ROX Analyzer (RA), an instrument that measures ROX. The RA exposes blood to a programmable stress profile made up of mechanical shear stress, followed by chemical or other stresses. The RA produces reproducible and uniform data which measure the amount of ROX available, and the rate at which WBCs produce new ROX—how much ROX we have, and how much ROX we can make.

SUPPLEMENTAL ROX

We can produce ROX supplements for those who lack sufficient amounts. We can measure how much ROX one can produce and how much ROX one already stores, in order to supply the correct amount.

WHY IS ROX IMPORTANT

Medical emergencies and serious accidents can lead to stress, which reduces both the available ROX, and the capability to make new ROX. ROX depletion can be caused by the stresses due to over-exhaustion, air pollution, and emotional pressures, all of which consume large amounts of oxygen. Depletion of ROX leads to inhibition of physical and muscular mobility, interference with good decision-making, and vulnerability to diseases such as ALS, PTSD, cancer, diabetes, and inflammation. Keeping ROX in balance will greatly improve mental and physical performance.