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Pulsatile OR steady flow, which is better?

#usefulinfo #organperfusion #cellularperfusion #beatingflow




Hello.


I am Kazunori, the developer of Organ Perfusion system. I am the kind of engineer always seeking the new and best perfusion mechanism for samples from the morning (sometimes work till dawn).

In this article, I would like to address the one perpetual challenge for perfusion, which is the suitable perfusion, Pulsatile or Steady-state flow?

I hope this article will answers to your following questions.

"What are the advantages and disadvantages of pulsatile and steady flow."

"What is the pulsating?"

"Which is better in a perfusion experiment?"


Table of Contents

  1. What is pulsatile flow?

  2. What is steady-state flow?

  3. In the field of the artificial heart

  4. The view from the vascular side

  5. How is an isolated organ?

  6. Summary

What is pulsatile flow?



The pulsatile flow is often referring as "flow of pulse."

What is the pulse? (see information from Wikipedia)

" In medicine, a pulse represents the tactile arterial palpation of the cardiac cycle (heartbeat) by trained fingertips." (Wikipedia, https://en.wikipedia.org/wiki/Pulse). According to this information, it seems to me that the flow created by that movement is called the pulsatile flow.



What is steady-state flow?



In contrast, steady-state flow is a general method of delivering fluid at a constant rate. In this article, we often use the term "non-beating flow" to distinguishing it with pulsating flow.


As you know and experience, it is quite difficult to perform a perfect steady-state flow in the isolated organ perfusion because it uses a roller pump. To achieve steady-state flow, it requires a lot of efforts and patience. We will describe these problems and challenges in another article.

TokaiHit offers a constant pressure feeding units that can use to pump fluids at constant pressure as one of product lineup, too.



Constant Pressure Feeding Unit

OCS-BPU Pat.P

Constant pressure perfusion can be achieved while monitoring the pressure of the flow path.

Click here for details

Click here for an approximate price



In the field of the artificial (mechanical) heart.



In the history of the artificial heart, the question of whether the pump should drive by pulsatile or steady-state flow create the debated for a long time, and still even today.

The first artificial heart has reported by Akutsu, Corfu, et al. in 1957, and it was using pulsatile perfusion. Since then, the pulsatile flow has been the mainstream.

In my opinion, the actual heart perfuses the system via pulsatile mechanism. The fist artificial heart was developed by mimicking this heart pulsatile flow work mechanism.

However, later in animal studies in the United States, they had reported that "The animals survived for three months, even with the no-beating flow (steady-state flow)."

Due to these results, it reported that people started to apply the non-pulse mechanism to artificial heart (from the web page of National Accreditation Service accessed on June 25, 2020, http://www.ncvc.go.jp/cvdinfo/pamphlet/heart/pamph42.html# anchor-4).

Currently, both pulsating and steady flow are used for artificial heart these days.


From the vascular side view



In my opinion, for the vascular endothelial cells, the pulsatile flow seems to be somehow more suitable. This is because especially arterial vessel exposed to the pulsatile flow in the body environment all the time. Due to this reason, I would imagine that that the pulsatile flow has a positive effect on the blood vessels

Much investigation has done in the field of mechanobiology, especially in vascular endothelial cells.

The keyword "endothelial pulsatile" in Google Scholar search results approximately 22,700 references (accessed June 25, 2020 Google Scholar

https://scholar.google.co.jp/scholar?(hl=en&as_sdt=0%2C5&q=endothelial+pulsatile&btnG=).

Ando et al. suggesting "for the same strength of shear stress, the effect of pulsatile flow is generally greater than that of steady flow" in their article(Ando et al., Japanese Journal of Thrombosis and Haemostasis, Vol. 13, No. 3 https://www.jstage.jst.go.jp/article/ jjsth/13/3/13_3_3_227/_pdf).

So, from above results, for vascular, especially from the peripheral side, the pulsatile flow seems to be better.



How about in the isolated organs?



So, which perfusion is better for experiments on an isolated organ which stands in between the cell and the living organism?

It is getting more and more maniacal. Yes, the question is: What is the suitable/best perfusion for ex-vivo organ?


To find this answer, I spent my days as a researcher at a medical university, both as a researcher and a working graduate student, and then summarized it in an academic paper.


The answer to this question is a bit complicated and not simple answer. I found that by applying pulsatile flow from outside the organ, I was able to obtain better results than with steady-state flow. The details of the scientific explanation and discussion will present in the following paper.

By applying pressure to the organs periodically from outside, it stimulates the pulsatile flow on the arteries vessels and entire organs perfused effectively which survived the organ for a long time of period.



Related article:

"Ex-vivo organ perfusion": application to muscular and skeletal studies

(14 days of long-term perfusion)




Academic article:

Intermittent application of external positive pressure helps to preserve organ viability during ex vivo perfusion and culture.



Of course, to achieve such results, it took a lot of trial and error, especially the improvement and experimentation of the devices. Please read more about experiment achievement in another article if you are interested.


Conclusion:

The mildly pulsatile and pressurized are efficient for organ perfusion.



Summary


The grand debate of "whether the pulsating or steady flow is better" is covered in this article.

To summarize the content.

・ The artificial heart has both pulsating and steady flow.

・ From a vascular point of view, the pulsatile flow looks better.

・ Mildly pulsatile pressurization to the isolated organ will assist to keep the condition and functions much better than only pulsatile or steady-state flow.

What did you think?

The question of perpetual challenge for perfusion, “which is the suitable perfusion, Pulsatile or Steady-state flow” is still inconclusive.

We hope that this article will be of some help to those who are researching such a field.



Author: Kazunori Sano, Ph.D.



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