European Journal of Cardiovascular Medicine

The autonomic nervous system (ANS) is structurally and functionally positioned to interface between the internal and external milieu, coordinating bodily functions to ensure homeostasis and adaptively respond to stress. It carries out various complex physiologic responses that are coordinated centrally and peripherally.

The ANS is composed of 2 anatomically and functionally distinct divisions, the sympathetic system and the parasympathetic system. Both systems are tonically active. Most of the tissues are innervated by both systems. Because the sympathetic system and the parasympathetic system typically have opposing effects on a given tissue, increasing the activity of one system while simultaneously decreasing the activity of the other results in very rapid and precise control of a tissue's function. The overall effect of the parasympathetic system is to conserve and store energy and to regulate basic body functions such as digestion and urination. It predominates during quiet, resting conditions (Rest and Digest). Among other important functions, it also decreases heart rate which helps to conserve energy under resting conditions. The role of Autonomic Nervous System at multiple interfaces in normal and abnormal physiology is emerging as a key mediator of pathophysiology in a range of complex disorders (anxiety and panic, chronic fatigue syndrome, regional pain syndromes, autonomic failure) and as a critical substrate underpinning the field of neuroradiology.

Ageing is associated with an increased dependency on sympathetic control of cardiac responses and reduced vagal responsiveness. The blunted vagal modulation of the heart may be related to altered neural vagal discharge to sino-atrial node or to a change in the ability of the cardiac pacemaker itself. Cardiac electrophysiological studies have demonstrated a progressive decline in Sino-atrial conduction and sinus node recovery time with age. Studies have revealed an increase in empty Schwann cell bands or reduced number of fibres in the vagus nerve among old subjects [1].

Reports of studies on age related changes in cardiovascular autonomic functions of human body are very few in the North –East India. Therefore, it is important to evaluate the Cardiovascular Parasympathetic functions in apparently healthy subjects of various age groups of Guwahati, the capital of Assam.

The cross-sectional study was carried out in one hundred and fifty healthy male subjects of Guwahati city.

Each subject taking part was explained about the procedure to be adapted in the research. All the subjects after a thorough understanding of the procedures to be adopted signed an informed consent form provided to them.

INCLUSION CRITERIA

The subjects selected were between the ages 20 years to 70 years. The subjects who were non-obese and without any signs of cardiovascular, respiratory, endocrinological, neurological, haematological & inflammatory diseases were selected for the study.

EXCLUSIONCRITERIA

The subjects with any of the following findings were excluded from the study:

1) Evidence of hypertension

2) Clinical signs of cardiac failure or ECG changes suggestive of arrhythmia, ischemia.

3) Subjects having diabetes mellitus, respiratory diseases, giddiness on standing, syncopal spells and visual disturbances.

4) Subjects receiving drugs that are known to interfere with cardiac function or respiratory functions such as beta blockers, sympathomimetic drugs, vasodilators and diuretics.

5) Associated disease or conditions known to affect autonomic function like Guillen Barre syndrome, Poliomyelitis, Diphtheria, Tuberculosis, Syphilis, Amyloidosis, Chronic renal failure.

6) Any disease condition affecting the autonomic nervous system.

METHODOF COLLECTION OF DATA

The subjects were instructed to come on empty stomach with overnight abstinence from coffee and tea or any form of exercise. All the tests were conducted between 8: 00 am to11:00am in cool and calm atmosphere at room temperature varying from 27⁰ to30⁰ Celsius. The subjects were asked to relax in supine position for 30 minutes in the examination room. All the subjects were subjected to recording of their physical anthropometry, various physiological parameters and autonomic function parameters.

All the subjects were subjected to a battery of three standard cardiovascular autonomic function tests as recommended by American Diabetic Association and performed as per methods described by Sir Roger Bannister [18].

1. Heart Rate Response During Deep Breathing:

The test can be best performed by breathing deeply at six breathes per minute and measuring the difference between maximum and minimum heart rates over a period of one minute [28]. The subjects were seated on the examination bed throughout the procedure and were connected to the limb leads of an ECG machine (BPL, 108T DIGI). ECG Lead II was then recorded continuously at a speed of 25 mm/sec while the subject breathed as instructed. The heart rate variability interval (R-R intervals between adjacent QRS complexes) was measured manually with a scale. The change in heart rate was calculated as the difference between the shortest and the longest R-R interval [3]. The ratio of the longest R-R interval and shortest R-R interval averaged over 6 cycles is called the E: I ratio.

E/I ratio=           Mean of longest R-R intervals during each expiration.

Mean of shortest R-R intervals during each inspiration

E: I ratio:           ≥ 1.21        Normal

2. Heart Rate Response to Standing:

The subject was first instructed about the test, the ECG limb leads are attached and he is asked to take rest in supine position for 5 minutes. Then he was asked to attain standing posture within3seconds.ContinuousECG recording by Lead II was done and the heart rate was measured from 15 seconds before to 60 seconds after the subject stood up which ensured that enough beats were captured. A marker was used to indicate the point at which the subject started to stand up. The heart rate response is expressed by the 30:15 ratio which is the ratio of the longest R-R interval measured at the 30th beat to the shortest R-R interval at the15th beat after standing [18].

3. Heart Rate Response to Valsalva Maneuver:

The equipment required for performance of the Valsalva maneuver consists of a standard mercury sphygmomanometer modified by attaching a mouthpiece to its rubber tube. The subject is asked to sit comfortably. A nose clip was applied and subject was asked to blow through the mouth piece attached to the mercury manometer for 15 seconds maintaining a pressure of 40mmHg. A small air leakage in the mouthpiece was done which ensured that the subject did not blow with his cheeks (open glottis method) [19]. Throughout the maneuver ECG (lead II) was recorded continuously and for 30 seconds after release of strain.

Statistical Analysis:

All statistical analysis is done by using SPSS software version. All values are represented as Mean + Standard Deviation (Mean + SD). Comparison of mean values of parameters between the five different groups is done by One Way ANOVA. p Value <0.05 is taken as significant. Linear regression and coefficient of determination (r2) were used to examine the strength of association between ageing and cardiovascular autonomic function parameters. The linear correlation coefficient is referred to as the Pearson product moment correlation coefficient.

The present study showed a gradual decrease in the 30:15 ratio (Table no.1) from Group I to Group V. The values were significantly lower in Group III, Group IV and Group V as compared to Group I and Group II i.e., after 40 years of age the values were significantly lower. Further it is seen that the mean 30:15 ratio in Group V is in the abnormal range (<1, according to Ewing and Clarke).

Our study is in accordance with the works of many workers [3, 5,6,9,11,12, 14, 16, and 17] who found that the heart rate response to standing (30:15 ratio) fell with increasing age.

The present study shows that the difference between maximum & minimum heart rate during deep breathing (Table no.2) showed a gradual decrease from Group I to Group V which is very highly significant(p=0.000). The values were significantly lower in Group III, Group IV and Group V compared to Group I and Group II. The values of Group I to Group IV are in the normal range. However, the mean value of the test in Group V (61-70 years) is in the border line range (according to Ewing and Clarke grading of autonomic function tests).

Our findings are in conformity with the earlier studies done [3, 4, 6, 9, 10, 11, 13, 16, 17] who found that the heart rate response to deep breathing fell with increasing age.

The present study shows that there is a very highly significant (p=0.000) gradual decrease in the Heart rate response to Valsalva maneuver (Valsalva Ratio) from Group I to Group V (Table 3). Also, it is seen that the values were significantly lower (Table C1) in Group IV and Group V compared to Group I, Group II, and Group III. There was no statistically significant difference between the values of Group IV and Group V. However, in Group V (61-70 years) the mean value of the test is in the border line range (according to Ewing and Clarke grading of autonomic function tests). These findings are in accordance with earlier studies [5, 7, 10, 11, 16, 17]

In our study, correlation (by Pearson correlation) of different parasympathetic nerve function parameters with age was analyzed and it was seen that the Heart rate response to standing i.e.,30:15ratio, Heart rate response to deep breathing and Valsalva ratio negatively correlated with age and all these relationships were statistically significant (p=0.01). These results are in accordance with other studies [7, 8, and 16]

The results of present study therefore show impairment of parasympathetic nerve functions in apparently healthy elderly subjects. This probably might be due to the fact that vagal tone is reduced gradually as age advances [21, 22].

The present study showed a gradual decrease in the 30:15 ratio (Table no.1) from Group I to Group V. The values were significantly lower in Group III, Group IV and Group V as compared to Group I and Group II i.e., after 40 years of age the values were significantly lower. Further it is seen that the mean 30:15 ratio in Group V is in the abnormal range (<1, according to Ewing and Clarke).

Our study is in accordance with the works of many workers [3, 5,6,9,11,12, 14, 16, and 17] who found that the heart rate response to standing (30:15 ratio) fell with increasing age.

The present study shows that the difference between maximum & minimum heart rate during deep breathing (Table no.2) showed a gradual decrease from Group I to Group V which is very highly significant(p=0.000). The values were significantly lower in Group III, Group IV and Group V compared to Group I and Group II. The values of Group I to Group IV are in the normal range. However, the mean value of the test in Group V (61-70 years) is in the border line range (according to Ewing and Clarke grading of autonomic function tests).

Our findings are in conformity with the earlier studies done [3, 4, 6, 9, 10, 11, 13, 16, 17] who found that the heart rate response to deep breathing fell with increasing age.

The present study shows that there is a very highly significant (p=0.000) gradual decrease in the Heart rate response to Valsalva maneuver (Valsalva Ratio) from Group I to Group V (Table 3). Also, it is seen that the values were significantly lower (Table C1) in Group IV and Group V compared to Group I, Group II, and Group III. There was no statistically significant difference between the values of Group IV and Group V. However, in Group V (61-70 years) the mean value of the test is in the border line range (according to Ewing and Clarke grading of autonomic function tests). These findings are in accordance with earlier studies [5, 7, 10, 11, 16, 17]

In our study, correlation (by Pearson correlation) of different parasympathetic nerve function parameters with age was analyzed and it was seen that the Heart rate response to standing i.e.,30:15ratio, Heart rate response to deep breathing and Valsalva ratio negatively correlated with age and all these relationships were statistically significant (p=0.01). These results are in accordance with other studies [7, 8, and 16]

The results of present study therefore show impairment of parasympathetic nerve functions in apparently healthy elderly subjects. This probably might be due to the fact that vagal tone is reduced gradually as age advances [21, 22].

The study was carried out to evaluate and compare the status of the cardiovascular parasympathetic functions in 150 healthy male subjects in the age group of 20yrs –70 yrs. of Guwahati city and to assess the effect of age on the same.

The standard bedside non- invasive Parasympathetic Function tests (Valsalva maneuver, Heartrate variation during deep breathing, and Heart rate response to standing) were performed in each subject. The results showed a significant reduction in autonomic function with increasing age of the subjects. This study thus demonstrated that in the diagnosis and treatment of autonomic-related diseases, physiological differences in the cardiovascular autonomic functions due to age should be considered. This also warrants the importance of adopting a healthy lifestyle with which restoration of balance in autonomic function is possible

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