CNA Conference - Dr. Dainius Pauza - Anatomy and histology of the cardiac nervous system

So our next presentation will be by Professor Daniel Powza. Uh, Professor Power is the uh the uh. A professor of anatomy at the University of Health Sciences in Kaunas, Lithuania, and uh he has a vast experience working with human anatomy of animals as well and has many, many years of working with human, um, neuroanatomy in particular, particularly of cardiac, uh, uh, the cardiac um system. And so he's gonna be talking to us about the anatomy and histology of the cardiac nervous system. And so now we'll have the presentation by Doctor Daniel Hausa. Well, I want to thank the organizers of this er Congress for the invitation to take part in, uh, and even, uh, so, so to be the first presenter in, in this, uh, in this Congress, so really it's a great uh honor to me, uh, to have my, my, my presentation and to start our congress with, uh, from my presentation. So the aim of my talk is just to demonstrate the anatomy of intrinsic cardiac nerve plexus in a human and to characterize the cardiac nerves and ganglia according to their chemical types since specific neuronal chemical markers implicate the possible function of intrinsic cardiac nerve fibers and ganglionic cells. At the beginning, I was very shortly to explain the methods, what we used to, in our lab and the labs and uh what is essence. So, uh, The main methods based on which, uh, we, uh, I demonstrate all images and I, uh, try to, uh, how to say, to substantiate my, my statements, so was based on a specific technique and, uh, by which we, uh, Apply the special solution for whole hearts, and we, in this way, we could reveal the, the total, uh, uh. Cardiac plexus, interesting cardiac plexus, uh, without any cutting any sections. As you see in this, uh, whole mount, uh, not the whole mound, but it just whole or, uh, total, uh, pressure inflated the heart that Uh, these methods based on cholinesterase, uh, histochemical reaction allows to follow the nerves from their axis, epicardium via, uh, so, uh, heart hylum and to the heart, uh, apex to the atria and so, so this really very good methods. Just to realize how this, uh, mass and extent in the, in the heart and how, uh, they meet the ganglia and so on, so on and so. Of course, this methods, uh, visualize entirely whole plexus and there's no possibility to differentiate these, uh, uh. Sympathetic with parasympathetic with sensory actions, what the context of these nests, uh, and so on. Uh, due to this, uh, um, uh, problems, we analyzed, uh, uh, the same, uh, whole amount of preparations, uh, doing immunochemical, uh, analysis, as you see, also was very successful. Um, uh, results and we could, uh, um, applying this, uh, uh, antibodies, we could, uh, identify, uh, nerves that, uh, the predomination of, uh, sympathetic, parasympathetic, you're just using different, uh, uh, neuronal markers, you, you could differentiate on the womb, uh. Uh, heart, this, uh, ganglia from what they are composed, which, uh, which type, chemical type of, of neuronal somata predominate in one or in another ganglia. So that's just examples of, uh, of, uh, of this, um, uh, immunochemical preparations total. Uh, they are not sections. This is not sections, it's just whole transmural, uh, wall can be, uh, observed. For instance, here we also visualize, um, uh, conductive, uh, cardiomyocytes, uh, and in this case, we could very, uh, how to say easily to identify what is, uh, the relationship between the nerves and the, uh, conducting. Um, your, your cells. So even we can, uh, you can look to the, to the ganglia also nicely, uh, visualizing different type of axons that axis, uh, separate, uh, uh. How to say bodies of neuro of neurons and you reach, uh, and you see uh with uh persons pathetic with uh positive focal anesterase with uh uh axons that containing typical sensory, uh, sensory substance and so on and so on. He's also see the general, uh, neuro marker for, for all, uh, uh, neuronal bodies and also for the aged, so. Uh, we also have some, some population of adrenergic, uh, nerve cells inside these, these, uh, these ganglia. So, uh, I would start, uh, from again from this, uh, it's a and it's, it's a still called Nestera preparations because they very evidently, uh, demonstrate what's happens and how nerves proceed in, uh, in, uh, in, in the epicardium after they access the, uh, the, uh, uh, the kylum, the epicardium and, um. And these, uh, nerves, uh, uh, extend in the epicardium by a very, very specific, uh, uh, pathways. These pathways mainly are formed by different, uh, uh, structures like auricles, like, uh, roots of, of blood vessels. So the Like, uh, uh, uh oppressed, uh, these nerves in the epicardium, and when you're looking, you see that they, they proceed like in specific, uh, pathways and they, these pathways always are topographically very persistent. I mean that in every, every heart you see the same. So we named this interesting nerve for extending within the epicardium by specific pathways as epicardial, epicardial ganglionated nerve roads or suplexi. As you see here, we More than 20 years ago, uh, coined this, uh, term, uh, subplexus. Uh, so every, uh, subplexus, uh, when these nerves access, uh, epicardium, every three, I, I would say regions. So, uh, first region is, uh, uh, just to direct extensions, uh, of these, uh, uh, mediastinal nerves or extracardiac nerves inside the Um, epicardium, and we call this like pre-gangliated nerves. You see this, in this area, the, these extensions of extracardiac nerves and epicardium, there's now almost, uh, ganglia. Later, they reached the area where ganglia all distributed with, this, uh, area where, uh, we named like epicardial ganglia field. Uh, a ganglionic field and the, uh, behind this, uh, epicardial ganglion field, we, we have, uh, again, mm, nerves extending in the epicardium and we call that like post-gangrenated nerves. So the quality of nerves before the ganglia and behind the ganglia is, uh, significantly different. And, uh, and every, the subplexus, uh, it's composed from such, uh, such pre-ganglionated epicardial ganglia and uh postgangonated, uh, postganglionated nerves. So, in humans set and epicardium nerve suplexi and numerously ganglius, as you see in this image on the dorsal side of uh left atrium, we have subplexi that they have a lot of, uh, uh, of ganglia and on, uh, another Places, uh, like in the, uh, anterior side of, uh, left, uh, uh, atrium, we have just, uh, extension of epicardial nerves to the, to the, uh, uh, to the, um, uh, coronary, uh, groove and almost no ganglia in this. He we we say that it's just non-ganglionated uh uh our long-term studies as I, as I, as I mentioned it more than 30 years, we, we, we studying uh anatomy of nerves inside the heart so what allow us to conclude that In humans and also in other mammalians, so the right action is supplied by nerves via three suplexi. So we have, uh, uh, two directions. One nerves after accessing the hard hilum, so they, uh, uh extend to the right atrium. On anterior side, and that's why we call the ventral right atrial, uh, subplexus. Another on the posterior side, and they extend as a dorsal right atrial. So this, uh, subplexi, they mainly distribute only on the right atrium. So, uh, left atrium is supplied by three subplexi, one on the ventral side that I already mentioned it. Uh, one, subplexus that's really very, very huge and well-developed and extent on, uh, lateral later, uh, so on, uh, on the posterior side, by the, this theory, it's called like martial ligament. You see here a lot of nerves pro proceed in this, in this ligament extend on the posterior side of left atrium and even, uh, how to say, uh, mm. Uh, jump through the coronary s itself with these nerves and extend on the left, uh, uh, left ventricle on the lateral or posterior, uh, side of the, the, diaphragmic side of, uh, of left, uh, ventricle. So, uh, another, it's, uh, middle, uh, dorsal, uh, subplexus, it's mainly distributed on the posterior side of left atrium extending from the heart hilum, and you see it's, uh, uh, the, uh. Regularly, uh, distributes only up to the coronary sulcus in the area of cru it's, uh, penetrate the in atrial septum and the proceed this nerves as endocardial one to the, to the area of, uh, uh, AV node. So, um, yes, in the ventricles, uh, just, uh, left ventricle, it's supplied by one subplexus. It's, uh, right coronary subplexus that, uh, extend between our ascending aorta or roots of aorta and, uh, uh, arterial, uh, conus and distribute in, in the anterior and lateral side of right, uh, of right ventricle. So, uh, in contrast to persistent topography, uh, mm, of, uh, subplexi, individual variability is proper to the structure organization of the human, uh, ganglionated, uh, subplexi. You see here, uh, Two hearts, and well, it's, it's very evident differences, uh, if we just try to compare. One case is we have a huge number of ganglia and other cases we have no ganglia, so topography is the same but structural organization, it's really, it's really, uh, always, uh, very, uh, different, different, and that's why. Uh, we say that's quite, uh, very specific for every heart. So it's you, again, uh, uh, dorsal, uh, right atrial suplexus, you see this, uh, pre, uh, ganglionic, uh, pre-ganglionated nerves, uh, a field of ganglia and how they are different in different parts and post-ganglionic nerves, they extend more or less always to the same direction, to the same, uh, areas of, uh, of the atria. Um, So what's uh very different? So, uh, individual variabilities is manifested in the ganglia number. Here in this histogram, you can see the differences, uh, in specific areas on the hard surface in the number of ganglia, and this is not in the absolute numbers, but that's in folds. You can imagine that sometimes in different areas, the differences can reach even 70 and even more. Uh, faults. That's really something very, um, uh, amazing and, uh, it's difficult to explain. Maybe this, this ganglia that perform the same function, so located in other places, but anyway, uh, if we look from the clinical point of view, that's very important to know this, that sometimes in, in one heart the, these ganglion located in one area, this area more or less, uh, shown here. In other cases, they are located in a, a bit in a different, uh, different, uh, uh sites. So this also the age-dependent differences in the number of, of hard ganji. So if we compare the infants, children, and, uh, and adults, so during this, uh, uh, period of time, up to 25 peasants is decrease in the number of ganglia. Finally, I just want to conclude that Uh, really, intracycardiac nerve plexus, usually others call it like a nerve system, may be regarded as a complex of seven neural suplexi. Innovation areas and target of distinct neural suplexi are specific. The accurate knowledge of this anatomy of this suplexi allows the accurate electrical stimulation, ablation, and the avoidance of ablation of these neural structures. That are of the vital importance in maintaining normal neural control of the heart rate, contractility, and coronary circulation. Variability in morphology of intrinsic card plexus as well as the quantitative neuronal differences within the human heart suggests that the human hearts are neuronanatomically unique and evidently differ from the heart of other mammalian. Uh, amazing exam so far. Thank you very much for your attention. Thank you, Doctor Pauza for that wonderful presentation. I, I really enjoyed it. I know the others on the panel also will agree with me. Those are very beautiful pictures you have there and it's always nice to be able to see the anatomy and how it correlates to the histology as well as what we do um in the cath lab. So thank you very much for, for that presentation. I want to remind our audience that um the chat box is, on your screen. If you can click that and put your questions in there. Doctor Puza will be able to address that as well. So that's, that's uh available for us to use. Doctor Puza, if you don't mind me asking you this question, um, you know, I'm a pediatric electrophysiologist. I'm interested in pediatrics. And you mentioned that um the uh the anatomy, at least the ganglion are very a little bit different in the pediatric population. Um, is there anything of this sort also in different types of people such as, such as athletes? Do you see any differences in people who have been athletes, um, uh, or any different, such, such as that? So could you, could you, uh, a bit repeat the question? I'm not sure that I understood the question. You, you talk about the variability, yes, but maybe you can simplify the question. So you mentioned about the variability in age groups. I'm wondering if there's a variability in the, the, um, The, the type of person it is, such as athletes versus non-athletes or, you know, um, you know, different races or things of this nature. OK, so, uh, regarding this variability, unfortunately uh the human material it's very, very hard to say difficult to obtain and um. What we just uh had at that time when we did the the examination so that uh in that methods and in that style so we have very limited number of them. So we just could uh group this samples, you know, newborns, children, and age that's all, uh, so really it's not enough one how to say city, it should be very international so to say what's differences between uh. Um, Different age groups, they really, it's not enough, uh, samples. We should, uh, you know, these samples are are very specific. They should be very, very fresh, and, uh, because if you know, longer time after that, uh, we always in doubt what, uh, all the obvious stains or no, and, and so, but from my experience, what I can say, of course, I expect huge differences in, in age. Uh, we, we had similar, uh, observation and experimental animals, so that's really What, what I said, this, this age-dependent differences as the species dependent differences, I expect that also, uh, gender-dependent differences also can be a very, very significant, but for this, we need, how to say, very, very international team that would be very numerous, uh, material for study. Yeah, thank you for that. Thank you. That's, that's very helpful. And so it makes me wonder, you know, that sometimes when we're doing these procedures, it's helpful to maybe uh do multiple um remapping perhaps uh to look and see where this person may have a little bit of a variance compared to what we usually, you know, we usually target. So that's, that's very helpful. Thank you very much for that. Yeah, yeah. Doctor Petra, maybe I can ask you as well in terms of histology and anatomy. I know later on you talk about the um preparatory um nests, you know, later on when he talks about Afib. Have you found any, any anatomical correlation between those preparatory nests and, you know, and, and, and the anatomy? Yes, it is a very important question. We have to think about it, that we, Doctor Pusser have been showing that, but we can see that the anatomy is, has a, a high variability. So it is necessary to have a functional way to see the innervation. And it's possible to get, to, to get a higher uh approximation by mapping the atrial fibrillation tests. Uh, we have been observing that in our places that, uh, uh, Professor Paula is showing the ganglionated black sizes, there is a high density of atrial fibrillation. So, in, uh, obviously, I think we may begin the procedure by anatomical landmarks and after this, if it's necessary to, to, to, to observe it. Response is necessary to do a mapping basically in functional activity of the ending of the neurons. And I think in this case, this part is very important to, to have the, uh, obviously to have the map, the functional mapping, to have the fraction action mapping, for example, that is the mapping of the atrial fibrillation tests. Wonderful, wonderful. Thank you. So just small comment. So what I understood from uh my, this long-term anatomical studies, uh, the ganglia have their location, but this location is not very precise. It can, you know, inside this, as I call ganglionated field. So this, uh, concentration, I mean, it's very little, very, uh, variable, but It's usually they're always in the same, as I say, topography is the same, but the structure organization of them it's very, very individual. And that's uh should be taken into account if you're trying to reach some effect and there's no effect, it can also be due to anatomical, how to say, popularity. So maybe it's just, uh, it's not simple to uh to find the exactly this, uh, this location because the, the area, as I said, they are not so, so small as we expect. Doctor Paza, have you had any opportunity to see, uh, human hearts post atrial fibrillation ablation? Very often, accidentally, the, uh, the vagal inputs are taken out as part of that procedure, and, you know, can you make any comment about what you see? Unfortunately, no, uh, that would be really as I said it would should be international project uh to after. To, to organize possibility to exam uh those uh uh heart that we had treated that after, you know, identifying the diseases and so on. So I just uh had the material that was completely not related to card uh cardiovascular disease. So I had no chance to to look at this casey yeah. Um, it looks like, uh, Doctor Mazda has a question asking if there's any attendance. Yes, there will be seeing attendance for you. Final question for Doctor, uh, Puza, if you don't mind me asking. I know you use quite a bit of immuno histological and chemical, you know, ways of tracking these ganglia. Are there other modalities that are available that you're, you're starting to use such as, you know, MRIs that can use uh to, to some kind of, some kind of staining CTs to, to, to kind of find these ganglia plexi? I'm just curious about that, um, other ways of finding them apart of the immunochemical histological ways of doing this. Um, actually, uh, yes, I think it's a very, very, very hard question. So, uh, you're talking it's possible somehow to identify, to visualize them without this, uh, anatomical histological procedures, yeah. The question is in essence in this, yeah, I, I suppose that really it's not easy. It's not easy. I just, I believe on anatomy. If we know anatomy, we should, uh, we should, uh, trust on, on, on this, uh, observations, and we should, uh, say that this areas, they are not very related to no fat fats and so on, but this area is full of, uh, of, of ganglia. And uh I think it's um I think it's impossible to identify them just looking once I call the system like invisible system in their heart so really it's so tiny but I look into the I'm looking at the at at echocardium as to neuro. How to say, little brain of the heart. So it's full of main uh structures from which extend nerves to the myocardium andocardium and so on. So what I try to explain very, very super, how to say, very, uh, superficially, but very in general, but, but what, that is really, so we should keep in mind we have 7. Our plexus can be considered as system or plexi, and this is just a question how we identify it. Thank you very, very much, Doctor Bazo. That was wonderful. Much, much appreciated. Thank you. OK. Thank you.