Hypertension and Autonomic Nervous System Function «HANS» study

Hypertension and Autonomic Nervous System Function
«HANS» study
dr. abd elmoneim m.mashaal
md cardiology
professor of cardiology,
National Heart Institute Embaba
ABSTRACT: The aim of this work is to study the Autonomic Nervous System function in early, pre-hypertension «Pre.H.» and in established hypertension «EH,» stages. The material of this study included 300 subjects with elevated B.P and 80 normaltensive subjects for comparison. Each subject was exposed to the following physiologic tests: change in posture, valsalva manoeuvre, mental stress, cold pressor, hyperventilation tests. The pharmacological tests included: Isoprinaline infusion, propranolol infusion, atropine sulphate infusion and isosorbid dinitrite sublingually.
Our finding revealed that the low pressure sensitive baroreoptors function was intact in Pre. H stages I & Il and the high pressure sensitive receptors function, is intact in Pre. H stage I. and is attenuated in pre H. stage II. Both functions were greatly impaired in E.H. also it revealed significant increase in the activity of the cerebral cardio-vascular autonomic centers «CVAC» at cortical, sub-cortical and medullary levels in the 3 stages. Beta1 and alph2 adrenergic receptors sensitivity increased significantlly in Pre H. stage II, while they were attenuated in «E.H.». The parasympathetic receptors function was intact, and the resting parasympathetic outflow was normal in Pre. H. stage I and
it increased in Pre. H. stage & E.H. The resting vascular tonicity increased significantly in the three stages.
The Echoc-doppler study revealed significant increase in lefl ventricular (L.V) . systolic function (F.S) mainly in Pre.H stages I & II, due to exaggerated contractility of the septal wall (S.W) and Posterior wall (PW), (P.W > S.W) the diastolic dysfunction of L.V appeared in Pre. H. stage II & E.H. (Reversed E/A ratio and significantly increase in
I.V.R.T.). The structural changes included significant increase in S.W & P.W thickness of L.V (S.W > P.W) and a significant decrease in right ventricular volume in E.H. A significant +ve correlation between the increased cerebral CVAC activities and the increased contractility of S.W & P.W. of the L.V and also with its diastolic dysfunction.
In concolusion, this study confirmed the important role of ANS in genesis and aggravation
of essential hypertensions. Also it revealed the value of utilizing the baroreflex function for determining the early stages of hypertension. Further more it demonstrated the cardiac functional and structural changes in various stages of hypertension which may be used as a diagnostic tool for assessing hypertension severity. In addition it may provide a rational approach for management of hypertension by the centrally acting antihypeitension drugs and the simultaneous use of alpha and beta-adrenergic blocking agent or agents.
THEMATERIALOF STUDY
the material of this study included 300 subjects with elevated B.p for 195 male and 105 female. their ages ranged from 30 - 60 with a mean of 47 year.
their S.B.P ranged from 140-200 mm Hg with a mean of 160 mm Hg, and their D.B.P ranged from 90 - 140 mm Hg with a mean of 130.4 mm Hg.
for comparison normotensive subjects were selected their ages ranged from 30 - 60 with a mean of 45.6 years their S.B.P ranged frome 120 - 130 with a mean of 121 mm
Hg, and their D.B.P ranged from 70 - 80 mm Hg with a mean of 79.8 mmHg. each subject was eposed to the following physiologic tests:
chane in posture, valsalva maneuver, mental stress, cold pressor, hyperventilation tests. the pharmacological tests included: isoprinaline infusion, propranolol infusion, atropine sulphate infusion and isosorbid dinitrite sublingually.
Material
Pt No: 300 Subjects with #B.P
Sex : 195 Males & 105 Females
Age: 30- 60 (47 ± 8.5)
SBP : 140 - 200 mm.Hg (160.5 ± 17)
DBP : 90 - 140 mm .Hg (130.4 ± 17)
Normotensive Subjects = 80 (41 males 39 Females)
Age: 30 - 60 (45.6 1 ± 5)
SBP : 120 - 130 mm .Hg (121 ± 15)
DBP : 70 — 80 mm.Hg (79.8 ± 9)
Methods of Study
Part I: For Studying The Baroreflex Function
Effect of Posturol change,
Valsalva Manoeuvre test
Atropine Sulphate Infusion test.
Part II- For Studying The Peripheral ANS
Mental Stress best, Cold Pressor test
Hyperventlatian lest
Part III.For Studying The Peripheral ANS
Isoprenaline Infusion 0.01 mg ,0.02, 0.03 mg/kg
atropine sulphate (.01 mg , 02, 0.03 mg/kg)
Propranolo infusion(0.1 mg kg.)
Valsalva ,manoeuvre test.
Part IV Included Echo-doppler studying
The Associated Functional and Structural Findings
All the subjects were selected from the outpatient clinic of imbaba Institute Hospital. The following criteria were fulfilled before including any Subject in the study:
1) The subject was neither. smoker nor drinker.
2) Absence of fever, any infection or rheumatic activity.
3) Absence of clinical evidence of thyrotoxicosis, diabetic neuritis.
4) Absence of unstable angina.
5) Absence of bronchial asthma.
6) Absence of irregular rhythm and conduction disturbances in ECG or heart rate less than 50
beats/min.
clinical evaluation of patient's with heart failure:
A detailed history was taken from each patient and included:
1- duration of elevated B.P documented from the patient's old records.
2) Previous hospitalization.
3) Family history of rheumatic heart disease, diabetes mellitus, thyrotoxicosis.
4) Infections and haemorrhages.
5) Any medications taken.
complete clinical examination was carried out including body weght and height .12 standard leads electrocardiogram were thken. Tow chest x-rays films, post anterior and lateral views were taken.
All the subjects had the following laboratory investigations: complete blood picture, complete urine analysis and erythrocyte sedimentation rate. Patients with elevated B.P were either untreated or had discontinued their therapy 1-2 days before the studies.
Methods of Study
The various tests for evaluating the autonomic nervous function in the present study were planned to be carried out on 4 consecutive days.
Day I: The effect of the following stimuli on the heart rate and blood pressure:
1) Change of posture: the effect of standing one and three minutes.
2) Valsalva manoeuvre.
3) Mental arithmetic test.
4) Cold pressor test.
5) Hyperventilation test.
6) isosorbid dinitrate sublingually 5 mg, 7.5 mg respectively.
Day II: Propranolol test to study the effect of beta adrenergic receptor blockade on heart rate.
Day III: Isoprenaline infusion test to study the effect of beta adrenergic receptor stimulatlion on the heart rate.
Day IV: atropine sulphate test to study the effect of parasympathetic blockade on the heart rate.
Details of the Individual Tests:
All the tests were performed in a quiet room with a minimal admission to the room to avoid disturbing the patient. All the tests were performed in the
morning three hours after a light breakfast with the patients resting comfortably in the supine position. Patients were instructed to abstain from taking any specific cardiac treatment, 3-5 days before the onset of the study and during the tests. The patients were reassured regarding the safety of the different tests made, in addition they have a detailed description of the procedure they are going to perform or the tests they are going to have.
ECG electrodes were connected to the patient, heart rate was
determined from lead II. The cuff of a sphygmomanometer was applied to the left arm of each individual and was left in place for the whole period of the procedure to allow for frequent recordings of arterial pressure.
During a Period of 15 minutes, frequent measurements of heart rates and blood pressures were carried out until the last three readings were almost constant. These readings were considered the control measurement, after which the particular tests were carried out.
Day I:
1) Change of posture: .
After basal heart rate and blood pressure were recorded, the subject was asked to stand up and heart rate and blood pressure were measured, 1 and 3 minutes after standing.
2) Valsalva manoeuvre test:
Control heart rate and blood pressure were recorded then the subject was asked to blow into a mercury manometer to a level of 40 mmHg for a period of 15 to 20 seconds. Heart rate and blood pressure were continuously recorded during blowing, on release and after release until they returned to the prestimulus level.
3) Stressful mental arithmetic test:
Basal heart rate and blood pressure were recorded. Serial substractions of seven from hundred were made by
the subject. During the test, the subject was harassed and confused; while continuous monitoring of heart rate
and recording of blood pressure were made.
4) Cold pressor test:
Control heart rate and blood pressure were recorded as previously described. Then the subject's free hand just above the wrist was placed into ice-cold water (4OC) and immersed for one minute, while the blood pressure and heart rate were recorded at half minute interval for 3 minutes.
5) Hyperventilation test:
The test was made by asking the subject to breathe as deeply and as fast as possible for a period of 15
seconds. Heart rate and blood pressure were recorded before, during and immediately after the test after 10 minutes.
6) isosorbid dinitrite 5 mg then 7.5 mg after 10 minutes.
Day II:
Propranolol hydrochloride test:
After control heart rate and blood pressure were recorded, then 0.1 mg/kg propranolol hydrochloride in 10 ml dextrose solution was given to the subject slowly intravenously over a period of 3-5 minutes.
Heart rate and blood pressure were recorded every one minute during the injection and five minutes
after the end of injection then every 10 minutes. Propranolol has a prolonged effect which continued for 40 minutes or
more.
Day III:
Isoprenaline infusion test:
Two ampoules of isoprenaline solution, each ampoule of 1 ml containing 200 micrograms (0.2 mg) isoprenaline substrate were added to 400 ml dextrose in water. Each drop of this mixture contained 0.05 microgram isoprenaline. The doses were adjusted to every subject's body weight to give the doses of 0.01, 0.02, 0.03 and 0.04 micro g/kg/min.
Basal heart rate and blood pressure were measured. Then the intravenous infusion was started while the subject was laying in bed. Heart rate and blood pressure were measured till they had stabilized for 5 minutes for every dose.
Day IV
Atropine test:
Each Subject was Placed in bed, a forearm vein was cannulated and a slow infusion of dextrose in water was begun. After recording the control heart rate and blood pressure, incremental doses of atropine sulphate 0.01, 0.02, 0.03 and 0.04 mg/kg were given intravenously via the infusion tubing at five minutes intervals, and heart rate and blood pressure were measured.
then 5 mg isosorbid dinitraite was taken sublingually while the heart rate and B.P were recorded continuously during and after complete drug absorption and heart rate and B.P return to pre-stimulus levels. then after 10 minutes a dose of 7.5 mg isosorbid dinitrite was taken sublingually with continuous heart rate and B.P recording until they return to prestimulus levels.
The subjects did not leave the laboratory room until their heart rates and blood pressure approached their control levels