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Comparative study of sympathetic activity in normal and preeclamptic pregnancy

Prachi K. Shelke^1*, Barkat Ali Thobani², Mrunal S. Phatak³

¹Assistant Professor, Department of Physiology, Sri Vasantrao Naik Government Medical College, Yavatmal, Maharashtra, INDIA.

²Associate Professor, ³Professor and Head, Department of Physiology, Indira Gandhi Government Medical College, Nagpur, Maharashtra, INDIA.

 

Abstract               Introduction: Abundant studies on the pathophysiologic mechanisms of Preeclampsia described that it is characterized by low circulating volume and high vascular resistance. This is exactly opposite of the hemodynamic changes that occur in normal pregnancy. It has been proposed that autonomic nervous system particularly sympathetic nervous system bring about these hemodynamic changes, but the exact role of autonomic control mechanism in pregnancy is poorly understood. So the study is conducted to evaluate and compare sympathetic functions in normal and preeclamptic pregnancy. Aim and Objectives: To compare the sympathetic activity in normal and preeclamptic pregnancy Material and Methods: Fifty normal pregnant and fifty preeclamptic pregnant females in the age group of 19-29 yrs were enrolled for the study after institutional ethical committee’s clearance was obtained. The cold pressor test and handgrip test performed on both the groups. The systolic and diastolic pressor response during the maneuver is noted and response compared between above two study groups. Result: In our study, we found that mean value of systolic and diastolic pressure response is significantly increased in cold pressor test in preeclamptic pregnant females as compared to normal one whereas in Handgrip test only diastolic pressure response is significantly increased in preeclamptic females. Discussion: A significantly increased vasoconstrictive response to a cold stimulus seen in preeclamptic females is a sign of an increased vascular reactivity, which is attributed to increased sympathetic activity. Increased blood pressure response in handgrip test can be explained by muscle metaboreflex which is activated by accumulation of metabolites, which were increased in preeclampsia as compared to normal pregnancy. Conclusion: From the study, we conclude that there is sympathetic over activity in preeclampsia as compared to normal pregnancy. It would be helpful in both preventive and control measures for this most common disorder of pregnancy.

Keywords: Autonomic function test, Cold pressor test, Handgrip test, Preeclampsia, Pregnancy.

 

INTRODUCTION

One of the well known complication, that commonly come across during pregnancy is Preeclampsia. Preeclampsia is defined as a pregnancy - specific disorder occurring after 20 weeks of gestation characterised by blood pressure of 140/90 mmHg or more for the first time in pregnancy, on two separate occasions and proteinuria of at least 0.3 g per 24 hours in a previously normotensive and non-proteinuric patient¹. It occurs in up to 10% of all pregnancies and it is a major contributor to maternal morbidity and mortality, perinatal death, preterm birth and fetal growth restriction. It develops in the second half of pregnancy and resolves shortly after delivery.² Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy. Abundant studies described that preeclampsia is characterized by low circulating volume and high vascular resistance, which is exactly opposite of the hemodynamic changes that occur in normal pregnancy i.e. decrease in mean arterial pressure and systemic vascular resistance and marked increase in circulating volume, heart rate and cardiac output. It has been proposed that autonomic nervous system bring about these hemodynamic changes. Cardiovascular adaptations during pregnancy are triggered by decrease in systemic vascular résistance. It results into a feedback response of increase in cardiovascular sympathetic drive to meet the higher circulatory demands of pregnancy. Defect in this feedback response results into preeclampsia.³ In short, the marked increase in sympathetic activity in latter months of pregnancy help to return the arterial pressure to non pregnant levels, but when there is excessive increase in sympathetic activity, hypertension develops⁴. Earlier study by Hans P. Schobel et al⁵ indicated that increase in peripheral vascular resistance and blood pressure seen in preeclampsia, was mediated by a substantial increase in sympathetic vasoconstrictor activity. The higher cardiac output in early pregnancy of women, developing preeclampsia later is due to significantly higher heart rate, which has been regarded as an early sign of increased sympathetic activity.² If preeclampsia (toxemia in pregnancy) is considered as an impairment of these hemodynamic alterations, one might expect differences in autonomic control mechanism of preeclampsia⁶. Methods for the assessment of autonomic circulatory control in humans have therefore been of great interest for researchers involved in the field of cardiovascular physiology in pregnancy. Schobel et al⁵ measured postganglionic action potentials in sympathetic nerve fibers in patients with preeclampsia. Greenwood et al found that vasomotor sympathetic activity increased in women with normal pregnancy and was even greater in hypertensive pregnant women.^7,8 The potential involvement of the autonomic nervous system particularly sympathetic nervous system using non invasive methods like cardiovascular reflex test in preeclampsia has, as far as we know, not been investigated much in Indian studies. Since the sympathetic nervous system also has an important adaptive influence on the circulation, we decided to evaluate sympathetic nervous function in preeclampsia, using standard noninvasive cardiovascular reflex test. i. e. cold pressor test and handgrip test. ^9,10 These noninvasive methods have the advantage of minimal risk for the mother and the fetus and repeated measurements can be possible in case of any error in values during procedure.²

 

AIMS AND OBJECTIVE

To compare the sympathetic activity in normal and preeclamptic pregnancy.

 

METHODS

It is a cross-sectional study, conducted between December 2009 and October 2011 on two groups of subjects. Group I - Normal pregnant group (n =50) and Group II – Preeclamptic pregnant group (n =50). Thus a total of 100 subjects were included in the study and the selection criterion was:

Preeclamptic pregnant Group (Group II)

Diagnosed cases of Preeclamptic pregnant females (n=50) in the third trimester of pregnancy in the age group of 18 to 29years, visiting Obstetrics and gynecology OPD (antenatal clinic) were selected for study. Preeclampsia is defined as a pregnancy - specific disorder occurring after 20 weeks of gestation characterised by blood pressure of 140/90 mmHg or higher and proteinuria of at least 0.3 g per 24 hours in a previously normotensive and non proteinuric patient.¹ All subjects selected were primigravida with no other complication of pregnancy.

Exclusion Criteria

Females with

1. Age group other than 18-29
2. Previous history of hypertension, hypotension, CVD, Diabetes mellitus, chronic renal failure, obesity, liver diseases, thyrotoxicosis, vascular diseases.
3. Multigravida, those < 28 weeks of gestation, multiple pregnancy, known cases of intrauterine growth retardation and Eclampsia (In case of pregnant subjects)
4. Smoking and alcoholics
5. Subjects taking drugs such as hypnotics or autonomic blockers were excluded from the study.

These exclusion criteria were applied to both study groups so as to exclude direct or indirect effects of the above mentioned factors on the parameters assessed.

Normal normotensive pregnant group (Group I)

For comparison separate group of normal normotensive pregnant females(n=50)of same trimester(third trimester),all primigravida belonging to the same age group(18-29yeras), similar height and weight, and having same ethnic group as that of preeclamptic pregnant group were enrolled in this group. The selection of this group was based on detail history, physical examination as same as that used for the preeclamptic pregnant group. They met same exclusion criteria as that of preeclamptic pregnant group.

Procedure

Before starting the study work, all participants were given detailed information about the project and every effort was taken to solve their queries. This was an attempt to establish a good rapport with the subjects and relieve their anxiety. Written informed consent was obtained from every subject. The subjects were instructed not to have coffee, tea cola 12 hours before the tests and were asked to have light breakfast two hours before the tests^.11,12 The subjects were asked to report either in the OPD or in the ward of Obstetrics and gynecology as per their convenience in the morning hours for measurement of anthropometric parameters. BP was measured with sphygmomanometer by the standard auscultatory Riva Rocci method and heart rate with the help of ECG machine with lead II, explained in details below. The cardiovascular autonomic tests performed are detailed below in the order of execution. These tests were demonstrated to the subjects.

Anthropometric Measurements

Standing Height

Standing Height of the subject was measured by simply making the subject stand against a wall on which the measuring scale was inscribed. The subject would stand on bare feet on a flat floor against the wall with both the feet parallel and with heels, buttocks and occiput touching the wall. The head was held erect with eyes aligned horizontally and ears vertically without tilt. Then with the help of plastic ruler, the top most point of the vertex was noted on the wall.¹³

Weight

Weight was measured with KRUPS weighing machine in light weight garments without foot wears.

Recording of blood pressure

The arterial blood pressure of each subject was recorded in the right brachial artery in sitting position with the patient’s arm at approximate heart level.¹⁴ The subjects were instructed to come after a night’s restful sleep, no strenuous physical activity to be performed for atleast 1 hour before recording the blood pressure. The entire procedure was explained and the patient made comfortable to allay rise in blood pressure due to anxiety, excitement or stress.^1,15,16 The blood pressure was measured with sphygmomanometer by the standard auscultatory Riva-Rocci method from the right upper arm. The systolic pressure was recorded as appearance of the Korotk off sounds (phase I) and the diastolic blood pressure recorded as the disappearance of the Korotkoff sounds (phase V⁾⁽¹⁷) Two readings were taken with a 15 minute rest period in between and the arithmetic average of the two readings was noted as the blood pressure of the subject.^18,19

Heart rate

The subject was asked to relax in supine position for 30 minutes. The resting heart rate was recorded on a standard ECG from lead II, at a paper speed of 25 mm/sec. Two readings were taken with a 15 minute rest period in between and the arithmetic average of the two readings was noted as the heart rate of the subject

HR=1500/R-R interval⁹

 

 

Materials

Sympathetic function tests will be carried out by using

1. Electro cardiograph
2. Sphygmomanometer
3. Hand grip dynamometer
4. Cold water (4-5 degree cel)
5. Thermometer

Tests for sympathetic functions

1. Cold pressor test
2. Handgrip test

Cold Pressor Test: (CPT)

The subject was seated comfortably and HR and BP were recorded in the same manner as mentioned above before the test. The CPT was performed by immersing the subject's one hand up to the wrist in ice cold water (4-5 degree celcius) for 1 minutes^20,21,22 Subjects were asked to avoid isometric contraction and performance of a Valsalva maneuver or hold expiration during the CPT.²³ The maximum reading of systolic and diastolic pressures was noted and compare with pretest readings^.22 Rise in the systolic and diastolic blood pressure was calculated by subtracting pretest reading from this maximum reading.

Hand grip Dynamometer Test (HGT)

The subject was seated comfortably and HR and BP were recorded in the same manner as mentioned above before starting the test. The subjects were explained about the procedure through self demonstration. The subjects were asked to perform Maximum Voluntary Contraction (MVC) by gripping the handgrip dynamometer, as hard as possible for few seconds and maximum force exerted was noted down. After giving rest for few minutes the subjects were made to perform test at 30% of maximal voluntary contraction by gripping the hand dynamometer for 3-5 minutes or till the subject could sustain the effort comfortably^.24 Systolic and diastolic blood pressure was recorded on the non exercising arm at interval of 30 seconds during the period of exercise. Rise in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the point just before the release of hand grip were noted. The response was considered as the difference between maximum BP obtained during exercise and the pre-exercise reading.²⁴ A rise in DBP of less than 10 mm Hg was defined as abnormal, 11-15 mm Hg as borderline and 16 mm Hg or more as normal^25,26

Statistical analysis^27,28

Statistical analysis of the observations was carried out using SSPS version 17.0. The data was expressed in terms of mean and standard deviation and inferential statistics was determined using the one way analysis of variance (ANOVA), Bonferroni’s multiple comparison tests and z test as appropriate. Also correlation between different parameters was determined by Pearson’s correlation coefficient. Statistical significance was tested at 5% and expressed in terms of ‘p’ value with p<0.05 = statistically significant.

 

OBSERVATION AND RESULTS

Following anthropometric parameters were assessed and autonomic function tests were carried out in each of the study groups.

Anthropometric parameters

1. Standing height
2. Weight
3. Body mass index (BMI)
4. Arterial blood pressure

The above table shows the age (in years) of the two groups of subjects expressed in terms of mean and standard deviation. There was no statistical difference in the mean age of pregnant (Group I) and preeclamptic pregnant women (Group II).

Table 3: Table showing group wise comparison of height, weight and BMI of subjects

 

Table 7: Table showing group wise comparison of the sympathetic activity of the subjects in two groups

Response of sympathetic function tests	Group I Normal pregnant	GroupII Preeclamptic Pregnant	Group I Vs Group II
Increase in SBP during CPT(mmHg)	13.52+4.908	15.92+5.450	P<0.05 *
Increase in DBP during CPT(mmHg)	9.040+3.574	10.96+3.923	P<0.05 *
Increase in SBP during Hg(mmHg)	13.4+4.005	14.96+-4.106	p>0.05 NS
Increased in DBP during Hg(mmHg)	11.68+-3.733	13.96+-4.703	P<0.05 *

 

DISCUSSION

This reflex stimulation (along with cortical irradiation) increases heart rate, causes arterial vasoconstriction in non exercising skeletal muscle, and increases cardiac output⁴¹. As explained in flow chart, concentration of local metabolite is inversely proportional to blood flow. Handgrip contraction causes decrease in skin blood flow. This decrease in blood flow is more in preeclampsia as compared to normal pregnancy⁴² resulting in more local metabolites production, which reflexly causes more stimulation of efferent sympathetic activity in preeclampsia as compared to normal pregnant. Other possible mechanisms given by some of the following studies. JOHN R. STRATTON et al³⁵ showed that plasma catecholamines, which are marker of general sympathetic nervous system activation, increases during handgrip exercise.. Preeclamptic group shows increased responsiveness to these vasoconstrictors due to increase sensitivity of vasculature to vasoconstrictors^32,33 whereas in pregnancy this responsiveness to vasoconstrictor is lost³² Thus, preeclamptic group shows significant increase blood pressure response, as sign of increased reactivity to stressor (handgrip) as compared to normal pregnant, suggesting increased sympathetic activity in preeclampsia as compared to normal pregnancy. Similar results were found in study by Nandini kapoor et al²⁴ John P Greenwood (2001) et al⁷ suggested some central role for increase sympathetic activity in hypertensive pregnancy. Pregnancy which later on, develops hypertension showed peripheral sympathetic hyperactivity^2,43.

 

SUMMARY AND CONCLUSIONS

The data obtained was subjected to statistical analysis. The findings of the present study are summarized as follows:

• The preeclamptic group is associated with a significant rise in the systolic, diastolic and mean arterial pressure as compared to normal pregnancy.
• Blood pressure response (i.e. rise in SBP and DBP) to cold stimuli and handgrip (i.e. rise in DBP) is significantly increased in preeclamptic group as compared to normal pregnant.
• Preeclampsia is associated with hyperactivity of sympathetic function.
• The development of preventive strategies not only requires knowledge of pathophysiology mechanism of the disease, but also availability of methods of early detection and means of interventions and correction of pathophysiological changes.
• Analysis of changes in baroreflex functioning serially in pregnancy and preeclampsia could be field of interest that should be further explored.
• As preeclampsia is found to be autonomic dysfunction disorder, then recent technique like pranayam and yoga could be beneficial in prevention of progress of disease as yoga practices bring about stable ANS equilibrium with tendency towards parasympathetic nervous system dominance and also cardiovascular efficiency is increased as many cardiovascular diseases are associated with it.
• Next to the application of preventive strategies, early prediction using the same autonomic functions could also be useful for targeting obstetrics care at those most likely to benefit.
•  

REFERENCES      

1. Report of the National High Blood pressure Education Program Group on High Blood pressure in Pregnancy. Am J Obstet Gynecol 2000; 183(1):S1-S22.
2. Rang S, Wolf H, Montfrans GA, Karemaker JM. Non invasive assessment of autonomic cardiovascular control in normal human pregnancy and pregnancy associated hypertensive disorders; a review. Journal of hypertension 2002; 20:2111-9.
3. Bosio PM, Mckenna PJ, Conroy R, O'Herlihy C. Maternal central hemodynamics in hypertensive disorders of pregnancy. Obstet Gynecol 1999 Dec;94(6):978-84
4. Fu Qi, Levine BD. Autonomic circulatory control during pregnancy in humans. Semin Reprod Med 2009 July; 27(4):330-7.
5. Schobel HP, Fischer T, Heuszer K, Geiger H, Schmieder RE. Preeclampsia- a state of sympathetic overactivity. N Engl J Med 1996 Nov 14; 335(20):1480-5.
6. Wouters EJM, Jaspers WJM, Kurver PJ, Dejong PA. Autonomic heart-rate control in response to standing in toxemic and normotensive primigravida pregnancies. Europ J Obstet Gynec reprod Biol 1984; 16:309-14.
7. Greenwood JP, Scott EM, Stoker JB, Walker JJ, Mary DASG. Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans. Circulation 2001; 104:2200-4.
8. Greenwood JP, Stoker JB, Walker JJ, Mary DASG. Sympathetic nerve discharge in normal pregnancy and pregnancy-induced hypertension. J Hypertens1998 May; 16(5):617-24.
9. Ghai CL. A textbook of Practical Physiology. 7th edition. New Delhi: Jaypee Brothers; 2007. Chapter 36, Autonomic nervous system (ANS) tests; p. 242-7.
10. Assessment: Clinical autonomic testing. Report of the therapeutics and technology assessment subcommittee of the American academy of neurology. American Academy of Neurology:1-4.
11. Bachlaus N. Measurement of baroreflex and sympathetic control of hemodynamic in mid pregnancy by orthostatic test. People’s Journal of Scientific Research 2010 Jan; Vol.3 (1):1-4.
12. Mourot L, Bouhaddi M, Regnard J. Effects of the cold pressor test on cardiac autonomic control in normal subjects. Physiol res 2009; 58:83-91.
13. Ghai OP, Jain V, Sankhyan N, Agrawal R. Normal growth and its disorders. In: Ghai OP, Paul VK, Bagga A, editors. Essential Pediatrics. 7th ed. New Delhi: CBS publishers and distributors; 2009. pp 1-21.
14. Garovic VD. Hypertension in pregnancy: diagnosis and treatment. Mayo clin Proc 2000; 75:1071-76.
15. The sixth report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Arch intern Med 1197; 157:2413-46.
16. Rubin P. Measuring diastolic blood pressure in pregnancy Use the fifth Korotkof sound. BMJ 1996 Jul 6; 313:4.
17. Ekholm E, Erkkola R, Hartiala J. Comparison of cardiovascular reflex tests and blood pressure measurement in prediction of pregnancy-induced hypertension. European Journal of Obstetrics and Gynecology and Reproductive Biology 1994; 54:37-41.
18. Diagnosis and management of preeclampsia and eclampsia. ACOG Practice Bulletin No 33. Obstet Gynecol 2002 Jan; 99:159-67.
19. The seventh report of the joint national committee on prevention detection, evaluation and treatment of high blood pressure. NIH 2003 December 03; 5233:1-34.
20. Godden JO, Roth GM, Hines EA, Schlegel JF. The changes in the intra-arterial pressure during immersion of the hand in ice-cold water. Circulation 1955 Dec; XII; 963-73.
21. Wood DL, Sheps SG, Elveback LR, Schirger A. Cold pressor test as a predictor of hypertension. Hypertension 1984; 6:301-6.
22. Kasagi F, Akahoshi M, Shimaoka K. Relation between cold pressor test and development of hypertension based on 28 year follow-up. Hypertension 1995; 25:71-6.
23. Victor RG, Leimbach WN, Jr, Seals DR, Wallin BG, Mark AL. Effects of the cold pressor test on muscle sympathetic nerve activity in humans. Hypertension 1987; 9:429-36.
24. Kapoor N, Sharma R, Ashat M, Huria A, Mishra G. Assessment of cardiovascular autonomic functions to predict development of pregnancy induced hypertension. NJOG 2011 May-June;6(1):41-5.
25. Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. Br Med J 1982 Oct 2; 285:916-8.
26. Jain AK. Manual of practical Physiology for M.B.B.S.1st ed. NewDelhi: Arya Publications; 2003.chapter 27, Autonomic nervous system (ANS) testing; p. 247-53.
27. Mahajan BK. Methods in Biostatistics. 6th ed. New Delhi: Jaypee; 1995.Chapter 9, significance of difference in means; p 130-156.
28. Mahajan BK. Methods in Biostatistics. 6th ed. New Delhi: Jaypee; 1995.Chapter 12, correlation and regression; p 186-204.
29. Woisetschläger C, Waldenhofer U, Bur A, Herkner H, Kiss H, Binder M, Laggner AN, Hirschl MM. Increased blood pressure response to the cold pressor test in pregnant women developing pre-eclampsia. Journal of Hypertension 2000 Apr;18(4):399-403.
30. Ponce de León RG, Ponce de León LG, Coviello A, De Vito E. Vascular maternal reactivity and neonatal size in normal pregnancy. Hypertension in pregnancy 2001; 20(3):243-56.
31. Garg S, Kumar A, Singh KD. Original Article: Blood pressure response to cold pressor test in the children of hypertensives Online Journal of Health and Allied Sciences 2010 Jan-Mar;9(1):1-3
32. Vanwijk MJ, Kublickiene K, Boer K, Vanbavel Ed. Review: Vascular function in preeclampsia. Cardiovasc Res 2000;47: 38-48
33. Gant NF, Worley RJ, Everett RB, Macdonald PC. Control of vascular responsiveness during human pregnancy. Kidney International 1980; 18:253-8.
34. Yamamoto K, Iwase S, Mano T. responses of sympathetic muscle nerve activity and cardiac output to the cold pressor test. Japanese journal of physiology 1992; 42:239-52.
35. Stratton JR, Halter JB, Hallstrom AP, Caldwell JH, Ritchie JL. Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects. JACC 1983 Jul; 2(1):93-104.
36. Kelsey RM, Patterson SM, Barnard M, Alpert BS. Consistency of haemodynamic responses to cold stress in adolescents. Hypertension 2000; 36:1013-7.
37. Kanayama N, Tsujimura R, She L, Maehara K, Terao T et al. Cold-induced stress stimulates the sympathetic nervous system, causing hypertension and proteinuria in rats. J Hypertens 1997 Apr; 15(4):383-9.
38. Baker PN, Johnson IR. The use of the hand-grip test for predicting pregnancy-induced hypertension. European Journal of Obstetrics and Gynecology and Reproductive Biology 1994; 56:169-72.
39. Tomoda S, Kitanaka T, Ogita S, Hidaka. Prediction of pregnancy-induced hypertension by isometric exercise. Asia Oceania J Obstet Gynaecol. 1994; 20(3):249-55.
40. Degani S, Abinader E, Eibschitz I, Oettinger M, Shapiro I, Sharf M. Isometric exercise test for predicting gestational hypertension. Obstet Gynecol 1985 May; 65(5):652-4.
41. Iellamo F, Pizzinelli P, Massaro M, Raimondi G, Peruzzi G, Legramante JM. Muscle metaboreflex contribution to sinus node regulation during static exercise: insight from spectral analysis of heart rate variability. Circulation 1999; 100:27-32.
42. Tur E, Tamir A, Guy RH. Cutaneous blood flow in gestational hypertension and normal pregnancy. J Invest Dermatol 1992; 99:310-4.
43. Airaksinen KEJ, Kirkinen P, Takkunen JT. Autonomic nervous dysfunction in severe pre-eclampsia. Europ J Obstet Gynec reprod Biol 1985; 19:269-76.

 




 

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