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This one above is really good. A long presentation of Oxidative Stress but the most concise and understandable one I have ever seen and done in the context of COVID 19. He says there will be another today. Can’t wait.

Notice the perception of this disease is shifting from “Respiratory Disease” to “vascular endothelial disease”, death of vascular endothelium exposes endothelial basement membrane. Endothelial Basement Membrane is highly thrombogenic which allows a small clot to form and “begin the healing process” (fibrin contraction and the mediators of inflammation migrating in drawing the cellular portions of the immune system). If you have many of these small clots more than a few are going to break loose and become micro emboli.

The Cardiac Output is 5 liters per minute, each heart beat produces an additional roughly 100 ml into the “vascular tree”. One liter of that output goes to the brain in the resting state. About 20 ml of each heart beat goes to the brain. ALL of that blood flows through the Internal Carotid Artery. The first place this blood flows to is what is referred to as the “Circle of Willis”. The ONLY chance arterial blood has of providing “Collateral circulation” to the brain. From the Circle of Willis on every artery in the brain is a “dead end”.

In the Operating Room when you can see the Circle of Willis Blood vessels you can SEE them absorb this 20 ml bolus of blood under pressure, the Peak Arterial Pressure is the top number of your systemic blood pressure so there is a pretty good head of pressure there and the vessels visible “throb”. Every breath you take “sucks” blood under negative pressure out of the veins in your head and so this “throb” of blood is literally sucked through the capillaries in brain tissue.

So, when micro emboli from the Pulmonary veins (the first stop of this virus after entering through lung tissue) return to the left side of the heart 20% of those micro emboli are going to be “pulsed” directly into the Circle of Willis under pressure. Cerebral blood flow is regulated to deliver the incoming blood to the places where it is needed and that coupling is 100%. The small blood vessels that perfuse the Thalamus and medial Temporal lobe perfume the parts of the brain that are involved in maintaining the wakening state and emotions and motivations for behavior. They get a very good share of this freshly arriving blood.

So the microemboli end up producing micro infarcts and some of this blood also carries viral particles. Your body’s clotting system is a “balance” of clotting and clot breaking and so your clot breaking enzymes start trying to break the clots up how well they succeed can determine the clinical progress of the disease. Direct viral attack on all the variety of cells available to the virus in this “mileux” produces the Necrotizing Encphalopathy seen in just these regions in the only MRI you can find on the internet.

I do think this does explain the “15%” of patients that present with Neurological Symptoms. If Mesial Temporal Lobe damage is a factor one could expect to see some pretty wild manifestations at “Critically Ill” stages of the disease.

So why focus on the brain? Because the Brain is the organ that has to be spared at all costs. Obviously. The question becomes at which stage of the manifestation of the Disease does this tend to occur? Obviously fairly early. We are still talking about microemboli, after all. At later stages the circulatory system is circulating much larger clots. Hence the “large Vessel Strokes” seen in kids. I suspect many, if not all, patients with “serious symptoms” would have an abnormal MRI even if they did not yet have Neurological symptoms. Remember the Neurological Symptoms to expect are subtle neurocognitive alterations of sensorium which in the context of a seriously ill patient aren’t going to be high on anybody’s list of priorities.

So what’s the point of all that? Well, any treatment that is going to be successful HAS to prevent this, what seems to me is probably a pretty characteristic presentation, serious brain injury which is likely already occurring in the seriously ill. It seems to me that no drug is going to get more than a few doses into the patient as all this is occurring. Certainly a drug that is administered IV will get maximal opportunity as it avoids all the pharmacokinetics of absorption, etc. it also has to have a MAJOR impact in those few doses to prevent death or serious disability. (Pretty obviously Remdisivir isn’t it, it has obviously been used in this context and if it was successful we would be hearing “reduces mortality” instead of “shortens hospital stays”)

It is fortunate that the disease progresses to this outcome so rarely.