AUTONOMIC  NERVOUS   SYSTEM  AND  THE  HEART

Prof. B. M. Hegde,
Vice Chancellor,
MAHE University,
MANIPAL–576 119.

                                                “There is more to it than what meets the eye”

Heart works non-stop throughout one’s life. Consequently, it must be under the control of the autonomic nervous system to a great extent. This article tries to unravel the mysteries of the latter control on one of the most exquisite organs of the human body, the heart, which had evoked so much interest even in philosophers and poets, that words like sweet-heart, hard hearted and large hearted were coined. The autonomic nervous system is both a friend and foe of man, thereby helping the “wisdom of the human body” to preserve itself under threats of disease and destruction.

This brings to mind the story of the man and the satyr of Aesop fame¹. When the two became friends they came to know one another better. When winter came and the cold increased man blew on his hands with his mouth. When satyr asked for the reason, the man replied that he was warming his hands. Later when they sat down to eat man was again blowing into the food kept in front. This time the satyr asked him again as to why he was blowing, the man replied that he was cooling the food, as it was too hot. “I am done with friendship with you, oh man, you blow hot and cold from the same mouth.” said satyr. It is said that it is better avoid friendship with those who blow hot and cold from the same mouth.

Nature, in its wisdom, thinks otherwise. Here is a system, which brings about two opposing effects on the contracting myocardium simultaneously in response to a single stimulus. This paradoxical system is absolutely necessary to tide over stressful events in life when the sympathetic system, through its beta-adrenergic agonists, increases the cardiac output both by increasing its stroke volume (positive inotropic action) and heart rate. (Positive chronotropic action).

More than those two functions, beta-agonists also increase the rate of relaxation of the heart muscle (positive lusitropic action); without which there could be a dangerous situation developing. If any excitement produces only increase in heart rate and force of contraction with the help of the sympathetic system, at very high rates there could hardly be any cardiac output with proportionately less filling in diastole. Nature again has made this versatile system respond to that demand by letting the beta-agonists increase the lusitropicity enabling the heart to maintain its diastolic filling time to a great extent intact or, at least, not reduced proportionately.²

Most of these effects are brought about by the mediation of cyclic adenosine monophosphate (cyclic AMP). In other words the typical response of the heart to the sympathetic stimulation is a more frequent rate of beating accompanied by a more forceful contraction but the latter is abbreviated to help fill the ventricle even at that higher rate of beating of the heart.

Writing in his article in The Journal of the American College of Cardiology, Arnold Katz, a noted cardiac physiologist, notes that “ the available evidence indicates that cyclic AMP influences several of the reactions, both active and passive, that are involved in the complex processes of excitation-contraction coupling, contraction, relaxation and production of the chemical energy utilized by many of these systems viz.” ¹

Beta-agonists binding to the receptor.

Activation of adenylate cyclase.

Increased cytosolic Cyclic AMP

Activation of cyclic AMP dependent protein kinase

Protein Phosphorylation

ALTERED FUNCTION.

Ventricular remodelling:

Myocardial infarction could be a serious blow to the heart’s function. More than 60% of those who have the first infarct probably die before they get to see anybody. They have the electric death. The remaining patients with good risk are the one’s that survive, many times even without any external help! Here again, it is the sympathetic system that helps the ventricle to rebuild itself, remodelling.

At the molecular level the sequence of events could be somewhat like this. At the centre of the infarct myocardial cells die, the surrounding cells respond to this cell death by coming to the help of the dead cells (cell slipping). The latter stimulates the fibroblasts in the cement that binds the cells together to give rise to fibrous tissue response. Those myocardial cells in the periphery that could not possibly slip to come to take the place of the dead cells in the centre try to help by getting themselves stronger to compensate for the loss of function of the dead cells. (Hypertrophy). So the processes of cell death, cell slipping, fibroblastic proliferation and the hypertrophy are all nature’s ways of compensating for the loss of function to keep the man going despite the disability suffered by him.

This whole process of remodelling is done through the help of the friend of man, the sympathetic system.The stimulus is mediated through beta-adrenergic stimuli. This has a moral for the treating physician. Very early drug treatment with drugs that block this normal phenomenon could be dangerous. But the compensatory mechanism has its inherent limitations. Beyond a particular point the compensatory mechanism could fail, and symptomatic heart failure develops. This may be a more appropriate time to initiate therapy. Doctors and their drugs and surgery could only assist body’s wisdom when it fails but not a substitute for it. This was amply shown in the AIRE³ and TRACE⁴ studies. In the former when ACE inhibitors were introduced only when signs of heart failure showed up after and infarct, in the latter TRACE study the drug was given immediately after the myocardial infarct, as a routine without waiting for the evidence of heart failure. The significant benefit that accrued in the former did not replicate in the latter study; even there was a possible trend towards harm done to the patients in the second study. Recent studies of the use of beta-blockers in heart failure have also confirmed the above belief. They should not be given in the acute phase of heart failure but should be introduced later for good benefit.⁵

Postural hypertension-an indicator of significance?

Normal arterial blood pressures checked lying and standing, show a fall in the systolic pressure by 10-20 mm Hg and a rise in diastolic pressure by 4-10 mm. Hg. on standing. In a series of normal people who underwent routine BP check up, it was noticed that a small percentage of them did have an abnormal response in that their diastolic pressure rise was more than 20 mm. Hg. When followed up for up to ten years majority of this small group had already become established hypertensives. Based on this a new hypothesis was proposed that these could be the one’s with hyper-responsive sympathetic systems. Although this study did not measure the metabolic end products of catecholamines lying and standing, it points to this possibility of the sign being an indicator of future onset of hypertension.⁶  If proved correct in any larger prospective study this could be used to detect children liable to get hypertension in later life so that their life style could be modified.

Ejection Fraction:

There is a tendency to depend, to a very great extent, on this non-invasive parameter to assess the ventricular function. Unfortunately this could only give a rough estimate of the ventricular function since the ultimate ratio between the stroke volume and the end-diastolic volume is determined as much by the extra myocardial causes as by the state of the myocardium. Here again the sympathetic system function-two major effects of extra myocardial variables- determine the two important determinants of the ejection fraction-heart rate and peripheral resistance.

In assessing left ventricular function after a heart attack it is more accurate to base the diagnosis on the level of symptoms on the bedside rather than the ejection fraction. The latter depends only partially on the state of the ventricular muscle function.⁷

Blood Loss:

Any sudden loss of blood resulting in fall in cardiac output it is the sympathetic system that helps the body to cope with it.    With the assistance of the beta-agonists the sympathetic system readjusts the circulation-constricting the vessels of supply to the less important organs like the skin while dilating the vessels going to the brain, heart and kidney-thereby protecting the vital organs till help arrives from some other source. Same changes occur when the stroke volume falls in early heart failure.

Parasympathetic effects on the heart:

Acetylcholine, the mediator of parasympathetic effect on the heart, has its greatest influence on the cells of the atria and the sino-atrial and atrio-ventricular nodes. Scientists have detected minimal effect of acetylcholine on the ventricular myocardium, but in clinical practice this is of no consequence. Due to its effect on the potassium conductances in the myocardium, acetylcholine slows the pacemaker activity of the SA node resulting in bradycardia. Enhancing potassium conductance by opening potassium channels it has its effect on the atrial muscle as well.  Similarly it has a very powerful effect to slow the conduction down the AV node. Very high concentrations could decrease conduction down the His-Purkinjee system as also the ventricular musculature.⁸

Science of Chaos:

Be that as it may, we have been so far using linear mathematics in medicine for research. In a dynamic system like the human body the linear relations do not hold good. No organ of the body, including the heart, could work in isolation. The heart, per force, has to work in tandem with other organs, mainly the lungs, as breathing is the most dominant rhythm in the human body. Using non-linear mathematics and the science of "chaos" one could get a better insight into the working of the heart vis-à-vis the lungs. Let us explore that area in the light of new knowledge coming in from that source.

Heart Rate Variability (HRV):

A child has sinus arrhythmia, which could be noticed even with the conventional ECG; the former gradually disappears as age advances. But if one analyses the dynamic ECG, one gets to see the "chaos" of normal HRV as against the smooth graph of the disappearing sinus arrhythmia in old age.⁹

The ancient Indian "praanaayaama" has been scientifically studied to see if the correct breathing methods followed in this ancient science could change one's HRV. Studies have shown the usefulness of this kind of breathing methods even in the treatment of resistant heart failure patients.¹⁰

We, in our own department, have shown a new method of studying the conventional ECG recording of 15 minutes duration using a polygraph. When this is analyzed using non-linear parameters, and specially designed computer models, we have been able to get very exciting data in this field.¹¹ Going from there to more complicated areas of cardiac diagnosis, we have obtained computer graphics of various disease states, with just the HRV data of fifteen minutes surface ECG, using the "Wavelet Analysis" methodology. The data look very promising and the Ph.D. theses are ready for final submission by a couple of my students. All these show how, in future, we would be able to diagnose complicated cardiac problems using simple bedside methods even in remote villages. HRV depends on the sympathetic and parasympathetic control of the heart and lungs. The new concept of "mode-Locking" is needed for the survival of all dynamic systems in this Universe. Most parameters of the heart's function have been shown to be "mode-locked" to breathing. In other words, proper breathing could influence even the subtle cardiac parameters like the ejection fraction, aortic pressure, pulmonary artery pressure, pre-load, after load, and even, tissue oxygenation.¹⁰

It is said that our ancient rishis have been able to live long. This looks probable in view of the capacity of proper breathing techniques to change the HRV of elderly people to that of a child. A proper balance of parasympathetic and sympathetic control on the heart and lungs should make man more tranquil and healthy! The future looks very promising in this field of research. Wisdom of the human body is amazing, to say the least.¹¹ Whereas we believe and teach that doctors are the one’s that bring about cure of diseases, the truth is otherwise. We could, at best, hasten the process of repair in any system but not make the system work the way we want. The more we know about the wonders of the working of this machine, the body, the more we appreciate the highly intricate system that keeps us going despite many a critical situation in life. I am reminded of the dictum of the father of modern medicine: “”cure rarely, comfort mostly, but console always.”  Doctors should always remember this and be humble. Nature and nurture together have kept man alive on this planet for the last 9,00,000 years in 50,000 generations.

“This world is not a wonder; it is a wonderful wonder!”
                                      Albert Einstein

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