심박수 변동성의 이해와 측정의 진화

### 심박수 변동성 이해의 진화: 1단계(1970~1980년대)
* 🧠 1970년대와 1980년대는 자율신경계에 대한 이해가 크게 발전한 **'생리학의 황금기'**였습니다.
* ❤ 생리학자들은 심박수 조절에서 부교감 신경계와 교감 신경계의 역할을 확인했으며, **안정 시 교감 신경계보다 미주 신경계가 더 큰 것**으로 나타났습니다.
* 🔄 심박변이도(HRV)는 심장 이식과 같은 실험을 통해 자율신경 연결이 끊어졌을 때 **심박수가 증가하고 변동성이 감소**하는 것을 확인했습니다.
* 📊 생리학자들은 **호흡 부비동 부정맥과 압력 반사를 포함한 HRV**를 정량화하기 위해 **시간 및 주파수 영역 측정법**을 개발했습니다.
* 🔢 프리즘이 빛을 분해하는 것과 유사한 주파수 영역 분석은 **HRV를 고주파, 저주파, 초저주파 및 초저주파 성분**으로 분류합니다.
* 🌡 다른 주파수 범위는 **고주파의 호흡 활동과 저주파의 혈관 활동**과 같은 특정 생리적 과정과 관련이 있었습니다.
* 📈 1970년대에 인체공학에 발표된 연구에서는 이미 이러한 주파수 구성 요소를 확인하여 **HRV에 대한 현장의 초기 이해**를 보여주었습니다.

심박수 변동성을 이해하면 5가지 중요한 과학적 단계를 통해 심박수의 진화를 알 수 있습니다.

and to sort of illustrate the way I interpret how heart rate variability has evolved over the years, I have put together the five stages, and this is based on the prevailing scientific paradigms that existed in each of these stages. Unfortunately, I won't be able to go through all of these five stages; it will probably take three talks overall to go over all of them. But you know, I think as of today, we'll just largely focus on part one: understanding heart rate variability. The stages are first understanding heart rate variability, and then heart rate variability as a marker of the autonomic nervous system, then heart rate variability as a marker of body-wide function, heart rate variability within the construct of mind-body interaction, and then finally the heart rate variability itself as a desirable target. So the first stage, understanding heart rate variability, happened in the 1970s and 1980s. Predominantly, there was a focus in physiology and the development of methods. In my view, the 1970s

and 1980s was the golden age of physiology. Uh, about, you know, this occurred about 20 years after Hodgkin and Huxley finalized their axon signal transduction had gone along the squid axons. This was also 20 years after Watson and Crick figured out the DNA double helix structure, and there was enough time for development of imaging stains such as ELISA in 1971, electrophysiology techniques such as voltage clamps, and machines that are important for obtaining electrophysiological measures, neural transmitter blockades such as atropine and propranolol, and you also have infrastructure for animal studies. So, it is only natural that you would see a significant development or advancement of our physiological understanding of the autonomic nervous system around this time. And by this time, by the 1970s, they really had a pretty good understanding of the autonomic nervous system, and they have divided it into two divisions. Actually, there are probably three because there's

the parasympathetic nervous system, the sympathetic nervous system, and the third one is the enteric nervous system, which we don't talk about too much here. Um, and during the 1970s and 80s, they've very much outlined the various physiological roles that each of these nervous systems play and also, importantly, understood the anatomical pathways that were responsible for the execution and functions of both of these nervous systems. In regards to the heart, we knew that the parasympathetic nerves slow heart rates and the sympathetic nerves increase heart rate. Now, the contracting functions of the heart are coordinated basically through the electrical conduction system, as depicted here in blue and purple. The part that sets the pace for the heartbeats is the sinoatrial node, or the SA node, located in the right atrium, and it helps sense the rate of the heartbeat. The conduction, the electrical conductions, you have

essentially, pacemaker cells in the SA node send electrical signals down the atrium to the AV node and then down the Purkinje fibers, the His-Purkinje cells, and then down the bundles that lead to the contractions of various chambers. Both the parasympathetic and the sympathetic nervous system act at the SA node and help set the rate of the heartbeat, and they both have sort of opposing effects. The sympathetic nervous system increases heart rate, which is shown here going up to 200 beats per minute. The vagal system, on the other hand, slows heart rate. And if you have exact cancellation of each other, and if you let the heart beat intrinsically on its own, the intrinsic heart rate is about 100-110 beats per minute. And since our resting heart rate is around 70 beats per minute, that indicates that the vagal tone is greater than the sympathetic tone at rest. And we knew that actually in the 1970s and even as early as the 1950s, actually was because um they

had done some experimentations with transplanted hearts, and you could see here the heart rate over time in a healthy heart. You can see that the average heart rate is about 71 beats per minute, and then when they transplanted the heart either in a dog or a human, you could see that the heart rate was much higher, about 99 beats per minute or even higher, 110 beats per minute. And the other thing that you know is that the variability that you see in the heart rate disappears in a transplanted heart. And the reason is that's the case is because the transplanted part, in order to transfer that part from the donor to the recipient, you need to disconnect all the autonomic nervous connections to that heart. So, that includes the parasympathetic nervous system, sympathetic nervous system, and so you lose this variability, and you have a significant rise in your heart rate. And this was known as early as the 1960s because the first human cardiac transplantation

was done by Christian Barnard in South Africa in December of 1967. So, we knew this way early on, and this is an example of sort of the complexity that you get with heart rate variability. This is our interval, which is the inverse of heart rate, and you can see the changes in the R interval with time or with the number of beats, and the average of this graph gives you the resting B2B interval, or in the analogy that I like to say, is sort of like the C level. The fluctuations that you can see around this quote-unquote sea level is the tides and the waves, and this is the heart and brake variability that we're talking about. And as early as the 1970s, clearly physiologists were able to identify the important factors that were involved in heart rate variability and even developed a schematic representation, and this is a pretty good representation, and this was a publication in 1973.

they've identified sort of the central neural controls, which included the brainstem control centers and triple mechanical factors, and they even developed a schematic to help understand how these various factors interacted with each other. And as noted, they identified the important factors, which included the control centers of the autonomic nervous system in the brainstem, the baroreceptors, which were important for maintaining a stable blood pressure, and also the effect of breathing by changing the intrapleural pressures. And so, they've clearly developed a very good understanding of this in the 1970s. And one of the important parts, sort of physiological contributions to this heart rate variability, is respiratory sinus arrhythmia. This is the change in your heart rate as you take a breath in and out. And you may notice as you breathe in, your heart rate, which is illustrated here by the gray, increases with inspiration or inhalation, and it goes down with exhalation. And there are certain sort of time dynamical time parameters or

information about the typical time scales is about every three to seven seconds that you take a breath or about nine to twenty-four cycles per minute. So this is the respiratory sinus arrhythmia, and then the other important physiological factor in heart rate variability is the baroreflex. The baroreflex is a way to control or stabilize blood pressure, and you have essentially these mechanical receptors located in the aorta and the carotid sinus. And then through the vagus nerve and the glossopharyngeal nerve, you have signals sent to the brain stem, and then this brainstem signals then gets sent to the autonomic nervous system nuclei, including the parasympathetic and the sympathetic systems, and then they feedback that response so that affects the SA node in other regions of the heart. The time scale for the baroreflex is a little longer; it's about three to twenty seconds, and it happens to be greatest problems approximately about six cycles per minute or every 10 seconds.

and around this time in the 1970s, in order to capture these variability dynamics, physiologists began to create multiple measures. And it's very hard to see sort of this in sort of granular detail here, but what's important to note is already by the 1970s, they've established important time domain measures and frequency domain measures. And this is a summation of the multiple heart rate variability measures that are out there in the literature right now. This was in Shaper in 2017. These are sort of highlighting the most important ones. There are at least 60 to 70 different heart rate variability measures now, and they're categorized into three big buckets. One is heart rate variability by the time domain measures, the second is heart rate variability by frequency domain measures, and the third one is non-linear measures. And I'm going to talk about each of these in a little more detail. The first one that I want to talk about is the

frequency domain, and the way I want to help you understand how this works is to sort of imagine light. So, if you take a prism and then you shine white light onto it, then the prism actually breaks down the white light into its different components of spectral light. You have different speeds of light secondary to the refraction within the prism, and as a result, it divides the light into its different frequencies. You could imagine that if you had a photo sensor in this wall, and you let that photo sensor accumulate the amount of light that goes onto that sensor over time, you would develop an idea of how strong each of these individual components of light are. You could do the same thing with heart rate time series, and we use different techniques, and sort of analogous to the prism, you have something called Fourier transform and auto-regressive spectrum analysis. There are some others as well, and what these techniques do is it permits us to identify the spectral power of each frequency range, so you can

Imagine this heart rate variability is composed of multiple signals with different frequencies, and these techniques enable us to sort of divide them and to identify which component is the strongest. And what you see here is you can essentially produce a spectral power, and you can see that the spectral power is divided according to the frequency. Now, frequency, the higher it is, that means the faster the cycle. So, the higher frequency is on the right here, and the lower frequency is on the left. And over time, we've got a pretty good understanding of the various categories of the cycles of the frequencies that are involved in heart rate variability, and we've divided them into several categories. There's high frequency, low frequency, very low frequency, and ultra-low frequency. And then we have a ratio of lower frequency versus high frequencies. And the frequencies that are associated with each of these frequency ranges are listed here. The ones that I want to have you pay attention to is the high frequency and the low frequency.

so high frequency is 0.5 to 0.4 hertz, which is about 9 to 24 cycles per minute. uh low frequency is three to nine cycles per minute. very low frequency is 25 seconds to five minutes per cycle, five minutes to 24 hours through the ultra-low frequencies per cycle. and in order to evaluate these cycles, you would need to acquire the heart rate over time. and because these cycles are shorter high frequency low frequency, oftentimes you just need five minutes in order to get information about these cycles, whereas for longer cycles, you would definitely need to require as long as 24 hours. and each of these cycles has physiological significance, so high frequency is associated with respiratory sinus rhythmia. the low frequency is associated with bare reflex and vascular sympathetic nerves um, and there's something called mirror waves, which is the oscillations, the intrinsic oscillations that you see in the vessels um, when I'm talking about the artery system. very low frequencies have slower physiological systems.

involved such as temperature regulation hormones such as region tension thyroxine reproductive forms and steroids and then the heart has an intrinsic nervous system as well which is believed to have a very low frequency range and then at the ultra-low frequency range it involves thermoregulation other hormones such as cortisol and growth hormones in the circulating rhythm and they knew a lot of this um as early as the 1970s and this is a publication in ergonomics and again they have created this frequency spectral analysis of heart rate variability and I'm going to read this to you because it may be small on your screen but they have already noticed that the respiratory activity is largely predominantly near 0.35 perch which falls into our high-frequency range the vase and mortar activity lies in the 0.1 hertz which lies in the low-frequency range and thermal activity at 0.025 hertz which is in the very low-frequency range so already they knew this in the 1970s

1.2 Fundamental HRV Physiology & Frequency Domain

Labfront

심박수 변동성(HRV)은 5단계에 걸쳐 발전해 왔으며, 첫 번째 단계는 1970년대와 1980년대에 HRV를 이해하는 데 중점을 두었습니다.

이 시기에는 자율 신경계에 대한 이해와 방법의 개발로 생리학이 크게 발전했습니다.

자율 신경계는 세 부분으로 나뉘었고, 그 생리적 역할과 해부학적 경로가 밝혀지면서 심박수를 조절하는 방법에 대한 이해가 더욱 명확해졌습니다.

심장 박동 조절에서 심박조율기 세포의 역할

SA 노드의 심박조율기 세포는 교감 신경계가 심박수를 증가시키고 부교감 신경계가 심박수를 감소시키는 전기 신호를 보내 심장 박동을 조절합니다.

고유 심박수는 분당 약 100~110회이고 안정 시 심박수는 분당 약 70회로, 안정 시 미주신경의 긴장도가 더 높음을 나타냅니다.

심장 이식은 자율 신경 연결을 방해하여 심박수를 높이고 변동성을 감소시키는데, 이는 1960년대부터 관찰된 현상입니다.

심박수 변동성에 대한 중추 신경 조절은 1970년대에 뇌간, 압력 수용체, 호흡 효과에 초점을 맞춰 밝혀졌습니다.

호흡 부비동 부정맥과 압력 반사는 주요 생리적 요인으로, 전자는 호흡을 통해 심박수에 영향을 미치고 후자는 혈압을 안정화시킵니다.

1970년대에는 심박수 변동성에 대한 여러 측정법이 확립되어 60~70가지의 다양한 측정법이 시간 영역, 주파수 영역, 비선형 측정법으로 분류되었습니다.

주파수 영역을 통한 심박수 변동성 이해

주파수 영역은 백색광을 스펙트럼 성분으로 분해하는 프리즘에 비유하여 이해할 수 있습니다.

푸리에 변환 및 자동 회귀 스펙트럼 분석과 같은 기술은 심박수 변동성에서 다양한 주파수 범위의 스펙트럼 파워를 식별하는 데 사용됩니다.

주파수는 고주파, 저주파, 매우 저주파, 초저파로 분류되며, 저주파 대 고주파의 비율에 중점을 둡니다.

심박수 변동성 주기는 주파수에 따라 분류됩니다.

4Hz)는 분당 9~24회, 저주파(분당 3~9회) 및 매우 저주파(분당 25초~5분)는 주기가 더 깁니다.

고주파 및 저주파 주기는 5분 이내에 평가할 수 있지만, 더 긴 주기는 최대 24시간이 소요될 수 있습니다.

각 주파수 범위는 생리학적으로 중요한 의미를 가지며, 고주파는 호흡 활동, 저주파는 혈관 및 교감 신경 활동과 관련이 있습니다.