The heart of the matter: Clinical electrophysiology and beyond


Clinical electrophysiology, the application of electricity to monitor or produce a physiological effect, seems such a core part of any modern hospital stay that it’s surprising how new it really is. Today, devices and techniques are more accurate and less invasive, making these lifesaving technologies  practically commonplace.


We spoke with Benjamin Scherlag, Professor of Medicine at the University of Oklahoma, USA, about his role in this part of medical history and why his dual roles in both clinical cardiology and basic science, have been so valuable.


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[00:00:06] Will Mountford


Hello, I’m Will. Welcome to ResearchPod.


Clinical electrophysiology, the application of electricity to monitor or produce a physiological effect in a person, seems such a core part of any modern hospital stay that it’s almost surprising to think of how new it really is.


As it stands today, devices and techniques have grown more accurate and less invasive, to the point that these lifesaving technologies are practically commonplace.


Today we’re speaking with Ben Scherlag, Professor of Medicine at the University of Oklahoma, USA, about his role in this part of medical history and why his dual roles in both clinical cardiology and basic science, have been so valuable.


Professor Scherlag, thank you so much for your time today and for taking this opportunity to talk with us.


[00:00:55] Benjamin Scherlag

Thank you for the opportunity to talk with you.


[00:00:59] Will Mountford

Just by way of introduction, if we could hear a brief biography and what are some of the personal highlights of your contributions in Physiology, electrophysiology, and research as a whole?


[00:01:10] Benjamin Scherlag

I received my PhD in 1964 at the Downstate Medical Centre in Brooklyn, New York. I did my postdoctoral work at Columbia University under the tutelage of Dr Brian Hoffman, who was at the time one of the, the foremost figure in cardiac electrophysiology.


[00:01:35] Benjamin Scherlag

Clinical electrophysiology was not known at that time. As a matter of fact, the work that I did, both at Columbia University and then at the Staten Island Public Health Service Hospital. We were able to do a singular type of work in which we used a catheter that we could introduce into the heart to record from a specific critical site of the cardiac conduction system called the His bundle, named after Wilhelm His. That lies between the upper chambers of heart and the lower chambers of the heart and conducts the electrical impulse from the upper to lower chambers; Causing the electrical activity and the mechanical activity of the heart.


[00:02:28] Benjamin Scherlag

And also the discovery of a means for electrical pacing of the heart. Either the Atria, the upper chambers or the lower chambers, which was done by, Dr Hein Wellens in the Netherlands. And those two kind of elements were the basis for a sub science of cardiology that became called Clinical Electrophysiology and this is what continues today as a means of recording from various parts of the heart and also ablating various abnormal structures in the heart in order to alleviate and actually cure in many cases cardiac arrhythmias, that is, disorders of the heart in patients.


[00:03:20] Will Mountford

From the inception of electrophysiology, through to today, has there been anything that has kept you engaged, kept you invested in the research?


[00:03:31] Benjamin Scherlag

There’s an interesting aspect to the recording, and that was an adjunct discovery that we made and that we could not only have that recording, but also pacing from the His bundle. At the time, we thought that that was a kind of interesting connection that people could use. It was used to some extent in the 70s, and then kind of faded away until the discovery in 2000 by Dr Pramod Deshmukh, in which what he did was, he took that catheter and he used it as a screw in lead that he could attach to the His bundle. So now he could do His bundle pacing and the interesting thing is. Using His bundle pacing for patients with heart failure.


[00:04:31] Benjamin Scherlag

Previously, what had been done was to put a catheter into the  left ventricle and another catheter in the right ventricle trying to synchronise the activity of the two chambers in order to get a much more effective ejection of blood so that the heart failure could be ameliorated. In this way with a single catheter one could produce this synchronisation and get the same kind of result or even better result with patients in heart failure. And that continues today it’s now become one of the major ways in which we do something called cardiac resynchronisation therapy.


[00:05:25] Will Mountford

Now, when it comes to clinical electrophysiology and also all of the lab work and your work as a physician.


How do you find that those kind of very disparate worlds of interacting with people, interacting with research and then interacting with microscopic, damn near atomic, detail of Physiology.


How do they relate to each other? Do they fit together? and have you found that one has helped your understanding of the other?


[00:05:54] Benjamin Scherlag

Well, it certainly was my good fortune that starting at the Staten Island Research Hospital. From that time until the present, I have always been collaborating with clinical electrophysiologists and til this day, I’m on the faculty at the Department of Medicine at University of Oklahoma Health Sciences Centre, and continue my collaboration with the faculty at the Cardiovascular Institute.


[00:06:28] Benjamin Scherlag

My continuation of research has not really been limited to the work that we did with the His bundle. What it really was, was a template for a continuing collaboration, so that we would do our basic science studies and then use that information to bring it to fruition in the clinical arena and that was why I continued to have this collaboration.


[00:07:05] Benjamin Scherlag

For example, in 1973 we came across another interesting structure in the heart which most people had thought to be a ligament. It’s called the Ligament of Marshall, discovered by John Marshall in 1850. But we found that there was a continuation of atrial tissue from the coronary sinus into this ligament the Marshall, and at the time it was just seemed to be a kind of recording that people could make. But eventually what happened again, the clinical electrophysiologist found that it was a critical area for the production of permanent and persistent atrial fibrillation and therefore it could be ablated very easily because there was a vein that ran within that Ligament the Marshall.


[00:08:04] Benjamin Scherlag

And Dr Valderrabano and his associates were able to inject alcohol into that vein so that they could destroy the ligament of Marshall,  and we called it a tract of atrial activity, which was the source of persistent atrial fibrillation. So that occurred only recently I think in the last three or four years. So this was another interesting aspect that occurred as a result of our basic studies in cardiac electrophysiology. This was not the only one that kind of followed this template.


[00:08:49] Benjamin Scherlag

The other one was a recent discovery by us, that we could stimulate the vagus nerve, which innervates the heart, through a noninvasive area called the tract the tragus. The tragus is the protuberance, the anterior protuberance of the ear and it has the auricular branch of the vagus nerve. So under those circumstances, we were able to show that the vagus nerve played a very important role in atrial fibrillation and again it became a means by which we could use stimulation, which was noninvasive, at the tragus of the ear in order to control atrial fibrillation. So this was another aspect of this template of connection between the basic science studies and the clinical electrophysiology.


[00:09:59] Will Mountford

Now I’ve got a note here regarding ganglionic plexi, is that leading into that?


[00:10:04] Benjamin Scherlag

Thank you for bringing it up. It goes back to the fact that I did a sabbatical in 1989 at the University of Montreal. Actually, it was at the hospital connected with McGill University. The discovery of the ganglionated plexi and these are neural structures which are found at the entrances of the pulmonary veins. Why is that important? Because again, let me give you a short history.


[00:10:35] Benjamin Scherlag

In 1998, Dr Haïssaguerre In France and his associates discovered that inflammation of the pulmonary veins was producing high levels of activity, which was then propagated into the atrium  and producing atrial fibrillation and what they did was they were able to take an electrode catheter, place it at the origin of these pulmonary veins so that they could, using radiofrequency energy, ablate the pulmonary vein entrances and in fact they were able to rid the patient of recurrences of atrial fibrillation.


[00:11:27] Benjamin Scherlag

The interesting thing that we found when we worked with Dr Andrew Armour in Montreal, he was the one who, with others, discovered these ganglionated plexi these collections of neural structures at the entrances of these pulmonary veins. And at the time he was interested in finding out how these structures would correlate with the mechanical activity in the heart. What we found was, actually we did these studies in 2000, 2004 and continued with our Chinese colleagues afterwards. That these ganglionated plexi, which were interesting, localised at the pulmonary veins were also sites of inflammatory activity that could cause atrial fibrillation.


[00:12:30] Benjamin Scherlag

So, we hypothesise that when Dr Haïssaguerre was ablating, the area of the entrances of the pulmonary veins, they were also ablating these ganglionated plexi, and therefore there was a definite connection between the ganglionated plexi and atrial fibrillation. The interesting thing, too, is that vagal stimulation, again from the tragus, could suppress this high activity of the ganglionated plexi.


[00:13:06] Will Mountford

What does tragus stimulation look like?


[00:13:09] Benjamin Scherlag

It’s very simple. You attach, actually, a connection to the tragus of the ear. So, it’s a little clip that you can put onto the ear, which actually will be able to stimulate the auricular branch of the vagus, which goes to a certain part of the brain and then goes down to the heart as well as to other parts of the body.


[00:13:35] Benjamin Scherlag

We are working with some people  in industry, Dr David Albert,and what we’ve done is created a system whereby one could record the electrocardiogram from the tragus so that you can actually see when atrial fibrillation will start, and then use that device to stimulate in order to suppress atrial fibrillation. We called it a closed loop system, and in fact we have a patent for that development.


[00:14:13] Will Mountford

Sounds like a much less invasive way of monitoring things.


I’m thinking you know something the size of a hearing aid to keep your heart going.


A lot of people would be very interested in that.


[00:14:22] Benjamin Scherlag

Yes, well, in fact, several people now are developing these non-invasive closed systems for stimulating and ablating the atrial fibrillation. To tragus stimulation that we started in 2004, if you look up PubMed. There are 300 articles relating tragus stimulation not only to atrial fibrillation, but also to epilepsy, and Alzheimer’s, and depression. So they now think that that because the auricular branch of the vagus not only goes to the viscera of the body, but also goes into the brain, and may have important effects in the brain.


[00:15:19] Will Mountford

Now your more recent work on the nonthermal plasma and plant biology, feels at a bit of a distance from clinical cardiology.


What brought about that shift in research focus?


[00:15:30] Benjamin Scherlag

We continued to do basic electrophysiology until, oh about four years ago. At that time, we kind of suffered from a political problem to terminate our animal studies. So under those circumstances we were again forced to go to a different area of research, that we had to leave my original interest,  I had a when I was an undergraduate.


[00:16:04] Benjamin Scherlag

I was very interested in Botany and Invertebrate Zoology. Until we were very fortunate to get some laboratory space in the Department of Physiology in order to start some studies that I was very anxious to do many years, but of course was not able to do because of my studies in cardiac electrophysiology. And so this actually became another area of this connection between basic science and clinical electrophysiology.


[00:16:39] Benjamin Scherlag

And so we started working with plants and animals. And our initial study was I believe was a singular discovery that we could produce something called plasma. Remarkably, we found that this hybrid plasma had anti-ageing, anti-oxidant and also anti-dehydration effects. So that we could use it for several applications. As a result of the studies that we did, we were able to attract the attention of the National Academy of Medicine that was running a Global Catalyst award, and we received one of those rewards for $50,000 that was back in 2020.


[00:17:35] Benjamin Scherlag

We now have, on the basis of our progressive research. We have now gone into the second iteration of the NAM contest and we are trying to show not only the very effects of anti-ageing, the anti-oxidant and then anti-dehydration effects in plants. We can now apply this to animals, we’re starting with some studies in in mice.


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