Thread by @CMichaelGibson

Thread

Provocative @Circulation article regarding the underlying cause of " #happyhypoxia " associated with #CoronaVirus where people have very low levels of oxygen but don't feel as short of breath like they usually would 1/n

ahajournals.org/doi/pdf/10.116…

@circulation The job of the lung is to transfer oxygen into the blood so that those oxygen rich red blood cells can deliver oxygen to the rest of your body.

If there is little or no oxygen in a part of your lung, would you want blood flowing to that part of the lung to pick up oxygen?

2/n

@circulation You would NOT want blood flowing to parts of the lung that have little or no oxygen.

Your body prevents this by using "Hypoxic Pulmonary Vasoconstriction (HPV); Hypoxic means no oxygen Pulmonary Vasoconstriction means you make arteries smaller which limits blood flow to a region

@circulation In other words, a healthy body constricts blood vessels and reduces blood flow to parts of the lung that have little or no oxygen for it to pick up.

What goes wrong in #coronavirus ?

@circulation These authors hypothesize that what goes wrong in #coronavirus is that your body DOES NOT reduce blood flow to parts of the lung that have little or no oxygen, so the blood is not maximizing its ability to pick up oxygen and therefore oxygen levels go down.

@circulation Why do your lung arteries fail to constrict? The authors hypothesize that it is due to an abnormality in the oxygen (redox) sensor in the lung arteries. In particular the mitochondria, the powerhouses of cells that control this are thought to be disrupted by #coronavirus.

@circulation It is notable that Some (not all) high blood pressure medicines interfere with the constriction of lung arteries, and recent papers show worse outcomes in people with high blood pressure. Sepsis also interferes with low oxygen mediated constriction of lung arteries & blood flow.

@circulation This concept of not turning blood flow down in areas of the lung with little or no oxygen has a medical name called ventilation perfusion mismatch (or V/Q mismatch for short).

@circulation Why do people do better and get better levels of oxygen when you turn them on their stomach (called proning)?

The authors hypothesize that there is a lot of variability in low oxygen artery constriction (HPV), & that proning reduces blood flow to those regions with bad HPV

For me, this was a moment of a bit of hand waving on the part of the authors: they don't provide a detailed explanation for the benefits of proning, which I have been eager to understand.

So blood is flowing just fine to areas of the lung where it cannot pick up oxygen, and that drive oxygen levels down.

Ok.

But why don't they FEEL short of breath like they should when their oxygen levels are really low?

Feel your neck for your pulse.

That is the carotid artery.

In the carotid artery there are oxygen (redox) sensors that drive your desire to breathe. Too little oxygen, the carotid body stimulates you to breathe.

These oxygen sensors are again, you got it: powered by mitochodria. Again, the authors hypothesize that #coronavirus has disrupted the mitochondria, disrupting the oxygen sensor, causing people to not feel short of breath, and to not breath faster & deeper as usual with low oxyg.

In high altitude sickness (High Altitude Pulmonary Edema of HAPE) the mechanism is the OPPOSITE of COVID: You get too much constriction of the lung arteries in some areas which raises the bleed pressure where the blood is actually flowing, damaging the little lung sacs (alveoli)

What does this mean for potential treatment? The authors say a drug called almitrine (which increases HPV and activates the carotid body) should be studied in trials. Care should be taken they say with calcium channel blockers which may block HPV.

I applaud the authors on providing some valuable hypotheses & ideas for further investigation. They did not really address the role of clots in the small arteries in the lungs which are being increasingly recognized as a cause of low oxygen & may also play a pivotal role.

Bravo