Pig brain function under extracorporeal pulsatile circulatory control
nature.com
nature.com
Impressive, really. But it's not even close to a brain in a vat, for the record.
> Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs.
So, as far as I understand: to control tracer liquid amounts more accurately, or deliver drugs to just the brain.
They seem to bring up theoretical concerns without addressing the practical (again, in human) successes of non-pulsatile flow.
I've worked in the LVAD and artificial heart industry, designed several.
You are right, that most modern LVADs are rotary pumps which are technically non pulsatile. I say technically because yes, if you test the pump on a bench of course it's not pulsatile. But once they're implanted, and working in concert with the native heart the net result is somewhere in between. You have more flow that you did before, less puksatile, but still pulsatile.
The implant guidance for most lvads calls for the clinicians to lower the speed setting of the lvad until they can see the aortic valve intermittently opening and closing on echo. If they set the setting too high and the valve stays open, or too low and it doesn't often open, it will calcify in one of those two positions.
If they follow this guidance, the net flow is pulsatile.
Onto your question.
Look up "pump head". This is what happens to the brain on truly non puksatile flow, like you get when your on extended periods of support on a heart lung bypass machine.
Check out a company "ventriflo" who is working on a pulsatile pump in this space to overcome these traditional challenges. I helped design this too.
Cheers!
The literature I'm familiar with doesn't suggest specific cognitive decline attributable to continuous flow vs pulsatile flow LVAD. Most likely, the consequences have to do with waves hands everything else going on and wash out if you have proper controls. For the briefer bypass for CABG, the literature does not clearly demonstrate a difference between on-pump and off-pump, but it seems to be an area of ongoing interest for the surgeons.
The failure of the aortic valve to open leads to thrombosis rather than calcification.
If the authors of the original post that we're discussing had run a comparison to a continuous-flow device and shown some sort of difference, then I'd be sold that their method is important. But since they are just comparing to the literature, the significance of the achievement remains unclear to me.
There is lots of literature here: https://en.m.wikipedia.org/wiki/Postperfusion_syndrome
>The failure of the aortic valve open leads to thrombosis not calcification. - Wrong. It can lead to both. Calcification is when calcium deposits build up and make it so the valve doesn't work, a lot like mineral deposits building up on your faucet valve and making it noe work anymore. Thrombosis is blood clotting. This can happen any time. Both of these things can happen, both aren't really related to eachother. They're both mutually exclusive, and often happen together.
There are known differences, see literature linked above.
Also, the timeframe for valvular calcification and thrombosis are not similar. Thrombosis is the killer when it comes to devices.
Same here, we don't have a lot of studies on this whole cutting a head off and keeping it alive. The closest two things we have are artificial hearts/lvads, and CPB pumps. It's reasonable for us to take those knowledge bases and like with the grass, learn the most from what we have.
You are right, those processes are different and as such have different time frames and clinical implications.
Another interesting point of note. Every artificial heart that is still implanted (Syncardia, Carmet), is about to start to ve implanted (Swedish realheart, bivacor) or has been implanted (abiocor, jarvik 7 which is now the syncardia, etc) were/are all fully pulsatile.
There is one case where Cohn and Frazier implanted a truly hand made bubble gum and duct tape pump made from 2 heartmate ii lvads fiberglassed together, that wasn't pulsatile but the patient was never expected to live long and it was really something they shouldn't have done.
I'm speaking from a design perspective.
When we design a pump, any pump, we need to design it to certain design inputs.
Say we're designing a well pump. We need the pump to pump a certain amount of water, a certain height, with a certain input power.
It's the same when we design LVADs or CBP pumps, peristaltic blood pumps for dialysis machines, etc.
One example. I lead the team that designed the peristaltic blood pump (and most of the whole system really) for the Outset medical Tablo kidney dialysis machine. I also have designed several other peristaltic pumps that pump other fluids. Pragmatically, the designs are almost identical. It's because pumps are pumps. The renal technician is going to say that the pump on their Gambro Dialysis machine is completely different than the pump in the Wendy's frosty machine down thr street, but the design engineer that designed them both knows better.
Back to this topic.
When we design a blood pump, it needs to meet certain design requirements. To test our design we need to model the body, it's response to inputs, etc. When we do this, we use the exact same models, exact same tools, exact same design principles, exact same process, amd exact same requirement s in many cases.
Indeed, no clinician would ever treat these things the same just like no mechanic would treat a Ford the same as a Toyota. But at the design level, they're the sake. They're both designed using the same CAD software, share many of the same suppliers and middle ware suppliers, etc.
I cannot stress how similar so many things are in medicine, in medical device design. So many people try to put up walls like this. It's not helpful to highlight differences, it's helpful to identify similarities, because that's where the economy of scale lieslies, that's where we can come together and solve problems.
Physics is physics, it doesn't magically stop just because it's in the body. Just because we put two identical things into use doing 2 different things, doesn't mean they're not the same.
A person with a back ache could be prescribed aspirin. Another person with blood clots could also be prescribed aspirin. Clinically these are very different things. The aspirin, and the factory that makes it, and the biochemistry by which it works, is the same.
Blood pumps are blood pumps, aspirin is aspirin. What you do with them clinically, and how, can vary widely. Agreed. But that doesn't mean the chemistry, physics, engineering behind them does too.
That doesn't seem to be exactly the same.
https://en.wikipedia.org/wiki/Postperfusion_syndrome says
> Physicians have theorized that the syndrome is caused by tiny debris and air bubbles (microemboli) that enter the brain via cardiopulmonary bypass
which doesn't seem to be related to the pulse, as such.
The linked article says
> current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity.
So to this layman, they're saying the nervous system behaves differently without the pulse, and the study the animal is being used for might suffer from those differences.
On the whole, it doesn't sound like a very nice procedure for the brain (or the rest of the pig)
2 pig subjects "were sedated with an intramuscular injection of tiletamine and zolazepam (4–8 mg/kg of each, in equal amount), atropine (0.04 mg/kg) and buprenorphine (0.05 mg/kg). They were then administered inhaled isoflurane, except during neurophysiological recording as noted below, and oxygen (2 L/min). These gases were applied first via snout mask and immediately afterwards via endotracheal intubation with mechanical ventilatory support. General anesthesia was maintained throughout the rest of the life of the animals, including euthanasia."
That protocol was approved by some suitable committee, in accordance with the Animal Welfare Act and similar protocols. I think most people informed of the details and the purpose of the research would agree the benefits easily justify the cost of their sacrifice.
The 'tragedy of animal testing' isn't -- at least as relates to food stock animals.
This doesn't work as absolution by itself: many past horrors we now find abhorrent were the societal norm at their time.
Tradition does not beget complacency, nor does it preclude reflection. I'm also eating bacon and eggs for breakfast, just the vegan versions, which are really good these days.
This strikes me as going too far.
the justification (upfront which is not as usual for most papers I come across which explain what they did that was so cool first) is something like it's hard to determine if what drugs we give to a brain is just brain based or is the darn body getting involved too.
But you know, if I understand that right, then we are mostly going to want to care about the brain and body together - cos that's how most of us function.
I get it's an engineering challenge. I also get that experimenting with certain things is just off-limits, foetuses being the first thing that come to mind.
I am a huge proponent for increasing science funding every day of the week, for undirected research because we don't know what we don't know, but sometimes we just need to say, find another way.
Someone can still be a strong proponent of the scientific method but be opposed to animal testing for moral reasons.
Any day. The pigs were anesthetized. A slaughter house is a positively horrific experience by contrast.