- Email: [email protected]
Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders
Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders Toshiyuki Hata, MD, PhD, a Kohkiehi Hata, MD, PhD, ~ and Kouzo Moritake, MD,
Phi) b
Izumo, Japan OBJECTIVE: Our objective was to compare maternal ophthalmic artery pulsatility index values in normotensive pregnancies and pregnancies complicated by hypertensive disorders. STUDY DESIGN- The ophthalmic artery in 17 normotensive nonpregnant women, 29 normotensive pregnant women, 9 patients with mild preeclampsia, 6 with severe preeclampsia, 6 with transient hypertension, and 9 with chronic hypertension was studied with color Doppler flow imaging and pulsed Doppler ultrasonography. The mean arterial blood pressure and the ophthalmic artery pulsatility index were calculated in each group. RESULTS: The pulsatility index (1.17 -+ 0.08) in severe preeclampsia was lowest among the groups p < 0.05), whereas that (2.92 -- 0.59) in normotensive pregnant women was highest among the groups (p < 0.05). The pulsatility index (1.47 _+ 0.30) in mild preeclampsia was significantly lower than that (1.89 + 0.27) in transient hypertension (p < 0.05). There was no significant difference in pulsatility index between mild preeclampsia and chronic hypertension (1.69 _+ 0.49) or between transient hypertension and chronic hypertension. The pulsatility index inversely correlated well with the mean arterial blood pressure (R2 = 0.645, p < 0.0001). CONCLUSIONS: These results suggest that the lower pulsatility index should be interpreted as orbital vascular vasodilation, indicating orbital hyperperfusion or hyperemia. Changes in pulsatility index in the ophthalmic artery may be indicative of similar changes in other cerebral vessels. (Am J Obstet Gynecol 1997;177:174-8.)
Key words: Ophthalmic artery, Doppler ultrasonography, pulsatility index, pregnancy, hypertensive disorder
Advances in perinatal care have substantially reduced the number of serious complications associated with high blood pressure during pregnancy. 1 The hypertensive disorders in pregnancy remain a major cause of maternal and fetal morbidity and mortality, as well as an area marked by substantial controversy concerning cause, pathophysiologic processes, and treatment, z-6 According to the classification suggested by The American College of Obstetricians and Gynecologists, hypertension associated with pregnancy falls into only four categories: preeclampsia and eclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, and late or transient hypertension. 1 Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. In spite of the ubiquity of the From the Departments of Obstetrics and Gynecologya and Neurosurgery,b Shimane Medical University. Received for publication June 12, 1996; revised November 6, 1996; accepted February 20, 199Z Reprint requests: Toshiyuki Hata, MD, PhD, Department of Obstetrics and Gynecology, Shimane Medical University, [zumo 693, Japan. Copyright © 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 4- 0 6/1/81382
174
disease and its public health impact, no comprehensive mechanism has been established. The most pathologically significant change in preeclampsia is thought to be arteriolar constriction in general organ systems. Ocular involvement has frequently been reported in this disorder. The visual system may be affected in 30% to 100% of patients with preeclampsia. 7 Some authors hypothesized that preeclampsia would be associated with elevations in orbital vascular resistance and hence with changes in the maternal ophthalmic artery flow velocity waveforms, s, 9 However, a decrease in orbital vascular resistance and an increase in orbital perfusion were noted in mild preeclampsia. These findings were the reverse of what might be expected from an elevated vascular resistance and hypoperfusion model. The aim of this study was to compare ophthalmic artery flow velocity waveforms in normotensive, transient hypertensive, chronic hypertensive, and mild or severe preeclamptic women to determine whether ophthalmic artery blood flow index values can accurately identify pregnancies complicated by, or destined to have, hypertensive disease.
Volume 177, Number 1 AmJ Obstet Gynecol
Material and methods Seventeen normotensive n o n p r e g n a n t women (aged 26 + 3.7 years), 29 uormotensive pregnant women ranging from 7 to 40 weeks of gestation, 9 women with mild preeclampsia (aged 27 + 4.5 years; parity 0.1 -+ 0.3; weight 59.9 -+ 4:9 kg), 6 women with severe preeclampsia (aged 29 + 5.7 years; parity 0.8 + 1.1; weight 58.1 -+ 2.4 kg), 6 women with transient hypertension (aged 27 -+ 4.1 years; parity 0.1 -+ 0.4; weight 71.1 _+ 15.1 kg), and 9 women with chronic hypertension (aged 34 _+ 7.3 years; parity 1.0 + 1.0; weight 67.6 _+ 16.7 kg) were studied with color Doppler flow imaging and pulsed Doppler ultrasonography. Preeclampsia was defined as an elevated blood pressure of ->140/90 m m Hg or a rise in systolic (>30 mm Hg) or diastolic (>15 mm Hg) values over the baseline blood pressure obtained before 16 weeks and proteinuria (2+) on dipstick. Severe preeclampsia was defined as an elevated blood pressure of ->160/110 mm Hg, the presence of central nervous system manifestations, or right-upper-quadrant pain (epigastric pain). Transient hypertension was defined as that hypertension alone developing (without proteinuria) in the last trimester or in the immediate puerperium but with the blood pressure returning to normal by the tenth postpartum day. The women with chronic hypertensive displayed elevated blood pressure before pregnancy or before 20 weeks' gestation. None of these chronic hypertension patients were maintained on antihypertensive medication before conception and throughout gestation. These women were nonsmokers, with neither indication of maternal complication nor incidence of drug administration. Those subjects with diabetes, multiple pregnancies, fetal hydrops, mole pregnancies, or eclampsia were excluded from the study. The preeclamptic and transient hypertensive subjects were evaluated before any intervention (i.e., administration of magnesium sulfate, epidural anesthesia, or antihypertensive medication). All subjects were evaluated in a cross-sectional manner. Gestational age was estimated from the first day of the last menstrual period and confirmed by first-trimester and early second-trimester ultrasonographic examinations (crown-rump length, biparietal diameter, and femur length measurements). The study was approved by the local ethical committee of Shimane Medical University, and standardized informed consent was obtained from each patient. As described previously,8' 0 the subjects were examined in a left lateral recumbent position with gel placed directly on the closed eyelid. The ophthalmic artery enters the optic foramen to lie lateral and slightly inferior to the optic nerve, then usually crosses superior to the optic nerve, and proceeds anteriorly on the medial side of the orbit, a° After the ophthalmic artery was identified on the medial side of the optic nerve approx-
Hata, Hata, and Moritake
175
imately 15 mm from the disk with color Doppler flow imaging, velocity waveforms were recorded over five cardiac cycles with pulsed Doppler ultrasonography with a 5 MHz microconvex transducer (Aloka SSD2000, Tokyo). In the color Doppler mode the flow directed toward the transducer was displayed in shades of red and the flow directed away from the transducer was in shades of blue. In the color and pulsed Doppler modes the lowest possible measurable velocity was 1.54 cm per second. Pulse repetition frequencies were 125 kHz, the maximum penetration depth was 12 cm, and the gate width used in this study was 3 mm. Wall filters (50 Hz) eliminated low-frequency signals occurring from vesselwall motion. An angle correction indicator was used to ensure an angle of insonation of the ophthalmic artery of <20 degrees during spectral analysis. The frequency shift was corrected for angle. Peak systolic velocities, enddiastolic velocities, time-averaged mean peak velocities, and pulsatility index (Pulsatility index = (Peak systolic velocity - End-diastolic velocity)/Time-averaged mean peak velocity) were averaged for each side. For statistical analysis, the mean pulsatility index was evaluated by averaging the values obtained from the right and left sides. Statistical analysis for comparison of these data among the groups was done with analysis of variance and the Newman-Keuls multiple comparison test2 A value of p < 0.05 was considered significant. The correlation between the mean arterial blood pressure (MAP) and the ophthalmic artery pulsatility index was analyzed by curvilinear regression.
Results The MAP values in severe preeclampsia or chronic hypertension was higher than those values in other groups (p < 0.05) (Table I). The MAP value in mild preeclampsia or transient hypertension was higher than that in normotensive n o n p r e g n a n t women or normotensive pregnant women (p < 0.05). There was no significant difference in MAP between normotensive nonpregn a n t women and normotensive pregnant women, those with mild preeclampsia or transient hypertension, or those with severe preeclampsia or chronic hypertension. As described previously,8 there was also no change in the pulsatility index associated with gestational age in normotensive pregnant women i n this study. The pulsatility index in severe preeclampsia was lowest among the groups (p < 0.05), whereas that in normotensive pregnant women was highest among the groups (p < 0.05) (Table I and F i g . 1). The pulsatility index in mild preeclampsia was significantly lower than that in transient hypertension (p < 0.05). There was no significant difference in the pulsatility index between mild preeclampsia and chronic hypertension or between transient hypertension and chronic hypertension. The pulsa-
176 Hata, Hata, and Moritake
July 1997 Am J Obstet Gynecol
.
4"
m
3
,~.
2
E
=.
a==
-i-
Normotensive nonpregnant
Normotensive pregnant
Mild preeclampsia
Severe preeclampsia
Transient hypertension
Chronic hypertension
Fig. 1. Ophthalmic artery pulsatility index in each hypertensive group. Horizontal bars, Mean pulsatility index value in each group. Table I. Mean b l o o d pressure and o p h t h a l m i c artery pulsatility index in each g r o u p Normotensive nonpregnant (n = 17) MAP (mm Hg)
OAPI
83 ± 8*,t,++,§
2.55 -+ 0.27",t,+,§,11 ,
Normolensive pregnant (n = 29)
Mild preeclampsia (n = 9)
79 _+ 911,¶,#,** 2.92 ± 0.59*,¶,#,**,tt
111 _ 9*,ll,tt,++,+
130 ± 7t,¶,tt,§§
1.47 + 0.30t,¶,++,§§
+#++ 1.17 ± 0 .08+, ,++,1111,¶¶
Severe preeclampsia (n =6)
OAPI, Ophthalmic artery pulsatility index.
*p < tP < Sp < §p < liP < ¶p < #p <
0.05. 0.05. 0.05. 0.05. 0.05. 0.05. 0.05.
**p < 0.05. ttP < 0.05. ,++*p< 0.05.
§§p < 0.05. III[P< 0.05. ¶¶p < 0.05.
tility i n d e x inversely correlated well with the MAP ( R 2 = 0.645, p < 0.0001) (Fig. 2).
Comment We previously r e p o r t e d that a decrease in orbital vascular resistance and an increase in orbital perfusion were evident in mild preeclampsia, a, 9 In this investigation the pulsatility index in severe preeclampsia was significantly lower than that in mild preeclampsia. This indicates that a decrease in orbital vascular resistance and an increase in orbital perfusion are m u c h stronger in severe preeclampsia than in mild preeclampsia. Easterling and Benedetti n p r o p o s e d that the effects of hyperperfusion are n o t limited to the brain and e x t e n d to systemic organs. These data support the c o n c e p t that
preeclampsia is a hyperdynamic condition in which the characteristic hypertension and proteinuria are mediated by renal hyperperfusion. T h e p r o p o s e d m o d e l of preeclampsia suggests a hyperdynamic disease in which increased cardiac o u t p u t and compensatory vasodilation mediate end-organ damage. If this m o d e l is to be consistent with clinical observations, h e m o d y n a m i c alterations must in some way lead to proteinuria and hypertension. These authors 11 also hypothesized that the hyperdynamic condition is associated with vasodilation of the g l o m e r u l a r afferent arteriole, which exposes capillaries to increased flow and mediates the d e v e l o p m e n t of hypertension and proteinuria. Kuo et al. 12 r e p o r t e d a decreased vascular resistance in maternal renal artery blood flow velocity waveforms in patients with mild
Volume 177, Number I AmJ Obstet Gynecol
Hata, Hata, and Moritake
140
e°
y = 173.06 - 48.380x + 5.7103x^2 •
•
177
R^2 = 0.645
0 °0
120
rgl
'-
100
o @
• o
;.¢:
80
60 0
I
1
I
I
I
1
2
3
4
5
Ophthalmic artery pulsatility index Fig. 2. Correlation between ophthalmic artery pulsatility index and mean blood pressure.
Transient hypertension (n= 6)
Chronic hypertension (n= 9)
109 -+ 4+,#,§§,HH 1.89 _+0.27§,**,§§,]111
122 + 8§,**,++++,HH 1.69 _+o.4911,tt,¶¶
preeclampsia. Zunker et al.13 described that the low pulsatility index in intracranial arterial blood flow velocities in patients with the preeclampsia-eclampsia syndrome suggests a forced vasodilation, probably resulting from passive overdistention of cerebral arterioles and vasogenic edema. These findings support the concept of forced vasodilation as a pathogenic key event associated with the preeclampsia. Furthermore, our study showed more severe hyperperfusion of orbital circulation in severe preeclampsia than in mild preeclampsia. This might explain the severe clinical manifestations, probably the result of severe hyperperfusion, in severe preeclampsia. On the other hand, vasodilation is a normal response to increased blood pressure. The body will vasodilate if blood pressure exceeds the set point. When hypertension is driven by high cardiac output, compensatory vasodilation is an active compensatory mechanism. This seems to be a more likely mechanism when low resistance is found in mild preeclampsia. Cerebral blood flow autoregulation normally operates
between MAPs of 60 to 150 mm Hg. 14 In this study all patients showed MAP in the range of 60 to 140 mm Hg, and a good inverse correlation between maternal MAP and ophthalmic artery pulsatility index was noted. This result support the idea that cerebral blood flow autoregulation operates well u n d e r the MAP of 150 mm Hg during pregnancy. Under these conditions, the yascular smooth muscle cells may reach the limit of strength and then yield? 3 Although short segments overdistended first, the whole length of the vessel will finally be affected. Beyond the upper limit of MAP, hypertensive encephalopathy may occur. In this study the pulsatility index in normotensive pregnant women is higher than in normotensive nonpregnant women. The reason for the pulsatility index in pregnancy being higher than in the n o n p r e g n a n t state is currently unknown. Although there is no significant difference in MAP between these two groups, the MAP in normotensive pregnant women is low. Therefore one possible explanation for this difference is that cerebral blood flow autoregulation may operate in normotensive pregnant women because a good inverse correlation between the MAP and the ophthalmic artery pulsatility index is evident in our study. However, in view of the relatively small n u m b e r of subjects, further study is needed to clarify this difference in ophthalmic artery pulsatility index between normotensive n o n p r e g n a n t and pregnant women. There have been a few reports on the assessment of cerebral and orbital circulations with Doppler ultrasonography in the preeclampsia-eclampsia syndrome,s, 9.13 However, there has been no report on the evaluation of orbital circulation with color Doppler flow imaging in
178
Hata, Hata, and Moritake
o t h e r hypertensive disorders during pregnancy. To the best of our knowledge, this is the first r e p o r t of orbital circulatory changes in o t h e r hypertensive disorders during pregnancy. Consequently, the pulsatility i n d e x value in transient hypertension or chronic hypertension was significantly lower than that in normotensive p r e g n a n t w o m e n but was significantly h i g h e r than in mild preeclampsia. T h e r e f o r e mild hyperperfusion in the orbital circulation was n o t e d in patients with transient hypertension or chronic hypertension d u r i n g pregnancy. T h e reason for these differences of the o p h t h a l m i c artery flow velocity waveforms between preeclampsia and o t h e r hypertensive disorders during p r e g n a n c y is currently unknown. O n e possible explanation is that the degree of vasodilation of cerebral arteries and the duration of disease process might be different between theses disorders. Further study is n e e d e d to clarify the m e c h a n i s m of cerebral circulatory h e m o d y n a m i c s in pregnancies complicated by hypertensive disorders. REFERENCES
1. Lindheimer MD, Katz AI. Current concepts: hypertension in pregnancy. N EnglJ Med 1985;313:675-80. 2. Chesley LC. Hypertensive disorders in pregnancy. New York: Appleton-Century-Crofts; 1978.
July 1997 Am J Obstet Gynecol
3. Gant NF, Worley RJ. Hypertension in pregnancy: concepts and management. New York: Appleton-Century-Crofts; 1980. 4. Lindheimer MD, Katz M. Hypertension and pregnancy. In: Genest J, Kuchel O, Pavel H, Cantin M, editors. Hypertension. 2nd ed. New York: McGraw-Hill; 1983. p. 889-913. 5. Ferris TE: How should hypertension during pregnancy be managed: an internist's approach. Med Clin North Am 1984;68:491-503. 6. Cunningham FG, Pritchard JA. How should hypertension during pregnancy be managed: experience at Parkland Memorial Hospital. Med Clin North Am 1984;68:505-26. 7. Jaffe G, Schatz H. Ocular manifestations of preeclampsia. A m J Ophthalmol 1987;103:309-15. 8. Hata T, Senoh D, Hata K, Kitao M. Ophthalmic artery velocimetry in pregnant women. Lancet 1992;340:182-3. 9. Hata T, Senoh D, Ha~a K, Kitao M. Ophthalmic artery velocimetry in preeclampsia. Gynecol Obstet Invest 1995;40: 32-5. 10. Erickson SJ, Hendrix LE, Massaro BM, Harris GJ, Lewandowski MF, Foley WD, et al. Color Doppler flow imaging of the normal and abnormal orbit. Radiology 1989;173:511-6. 11. Easterling TR, Benedetti TJ. Preeclampsia: a hyperdynamic disease model. Am J Obstet Gyneeol 1989;160:1447-53. 12. Kuo DM, Chiu TH, Hsieh TT. Maternal renal artery Doppler flow-velocity waveform in preeclampsia: a preliminary report. J Reprod Med 1993;38:189-92. 13. Zunker P, Ley-PozoJ, Louwen F, Sehuierer G, Holzgreve W, Ringelstein EB. Cerebral hemodynamics in pre-eclampsia/ eclampsia syndrome. Ultrasound Obstet Gynecol 1995;6: 411-5. 14. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990;2:161-92.
Phi) b
Izumo, Japan OBJECTIVE: Our objective was to compare maternal ophthalmic artery pulsatility index values in normotensive pregnancies and pregnancies complicated by hypertensive disorders. STUDY DESIGN- The ophthalmic artery in 17 normotensive nonpregnant women, 29 normotensive pregnant women, 9 patients with mild preeclampsia, 6 with severe preeclampsia, 6 with transient hypertension, and 9 with chronic hypertension was studied with color Doppler flow imaging and pulsed Doppler ultrasonography. The mean arterial blood pressure and the ophthalmic artery pulsatility index were calculated in each group. RESULTS: The pulsatility index (1.17 -+ 0.08) in severe preeclampsia was lowest among the groups p < 0.05), whereas that (2.92 -- 0.59) in normotensive pregnant women was highest among the groups (p < 0.05). The pulsatility index (1.47 _+ 0.30) in mild preeclampsia was significantly lower than that (1.89 + 0.27) in transient hypertension (p < 0.05). There was no significant difference in pulsatility index between mild preeclampsia and chronic hypertension (1.69 _+ 0.49) or between transient hypertension and chronic hypertension. The pulsatility index inversely correlated well with the mean arterial blood pressure (R2 = 0.645, p < 0.0001). CONCLUSIONS: These results suggest that the lower pulsatility index should be interpreted as orbital vascular vasodilation, indicating orbital hyperperfusion or hyperemia. Changes in pulsatility index in the ophthalmic artery may be indicative of similar changes in other cerebral vessels. (Am J Obstet Gynecol 1997;177:174-8.)
Key words: Ophthalmic artery, Doppler ultrasonography, pulsatility index, pregnancy, hypertensive disorder
Advances in perinatal care have substantially reduced the number of serious complications associated with high blood pressure during pregnancy. 1 The hypertensive disorders in pregnancy remain a major cause of maternal and fetal morbidity and mortality, as well as an area marked by substantial controversy concerning cause, pathophysiologic processes, and treatment, z-6 According to the classification suggested by The American College of Obstetricians and Gynecologists, hypertension associated with pregnancy falls into only four categories: preeclampsia and eclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, and late or transient hypertension. 1 Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. In spite of the ubiquity of the From the Departments of Obstetrics and Gynecologya and Neurosurgery,b Shimane Medical University. Received for publication June 12, 1996; revised November 6, 1996; accepted February 20, 199Z Reprint requests: Toshiyuki Hata, MD, PhD, Department of Obstetrics and Gynecology, Shimane Medical University, [zumo 693, Japan. Copyright © 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 4- 0 6/1/81382
174
disease and its public health impact, no comprehensive mechanism has been established. The most pathologically significant change in preeclampsia is thought to be arteriolar constriction in general organ systems. Ocular involvement has frequently been reported in this disorder. The visual system may be affected in 30% to 100% of patients with preeclampsia. 7 Some authors hypothesized that preeclampsia would be associated with elevations in orbital vascular resistance and hence with changes in the maternal ophthalmic artery flow velocity waveforms, s, 9 However, a decrease in orbital vascular resistance and an increase in orbital perfusion were noted in mild preeclampsia. These findings were the reverse of what might be expected from an elevated vascular resistance and hypoperfusion model. The aim of this study was to compare ophthalmic artery flow velocity waveforms in normotensive, transient hypertensive, chronic hypertensive, and mild or severe preeclamptic women to determine whether ophthalmic artery blood flow index values can accurately identify pregnancies complicated by, or destined to have, hypertensive disease.
Volume 177, Number 1 AmJ Obstet Gynecol
Material and methods Seventeen normotensive n o n p r e g n a n t women (aged 26 + 3.7 years), 29 uormotensive pregnant women ranging from 7 to 40 weeks of gestation, 9 women with mild preeclampsia (aged 27 + 4.5 years; parity 0.1 -+ 0.3; weight 59.9 -+ 4:9 kg), 6 women with severe preeclampsia (aged 29 + 5.7 years; parity 0.8 + 1.1; weight 58.1 -+ 2.4 kg), 6 women with transient hypertension (aged 27 -+ 4.1 years; parity 0.1 -+ 0.4; weight 71.1 _+ 15.1 kg), and 9 women with chronic hypertension (aged 34 _+ 7.3 years; parity 1.0 + 1.0; weight 67.6 _+ 16.7 kg) were studied with color Doppler flow imaging and pulsed Doppler ultrasonography. Preeclampsia was defined as an elevated blood pressure of ->140/90 m m Hg or a rise in systolic (>30 mm Hg) or diastolic (>15 mm Hg) values over the baseline blood pressure obtained before 16 weeks and proteinuria (2+) on dipstick. Severe preeclampsia was defined as an elevated blood pressure of ->160/110 mm Hg, the presence of central nervous system manifestations, or right-upper-quadrant pain (epigastric pain). Transient hypertension was defined as that hypertension alone developing (without proteinuria) in the last trimester or in the immediate puerperium but with the blood pressure returning to normal by the tenth postpartum day. The women with chronic hypertensive displayed elevated blood pressure before pregnancy or before 20 weeks' gestation. None of these chronic hypertension patients were maintained on antihypertensive medication before conception and throughout gestation. These women were nonsmokers, with neither indication of maternal complication nor incidence of drug administration. Those subjects with diabetes, multiple pregnancies, fetal hydrops, mole pregnancies, or eclampsia were excluded from the study. The preeclamptic and transient hypertensive subjects were evaluated before any intervention (i.e., administration of magnesium sulfate, epidural anesthesia, or antihypertensive medication). All subjects were evaluated in a cross-sectional manner. Gestational age was estimated from the first day of the last menstrual period and confirmed by first-trimester and early second-trimester ultrasonographic examinations (crown-rump length, biparietal diameter, and femur length measurements). The study was approved by the local ethical committee of Shimane Medical University, and standardized informed consent was obtained from each patient. As described previously,8' 0 the subjects were examined in a left lateral recumbent position with gel placed directly on the closed eyelid. The ophthalmic artery enters the optic foramen to lie lateral and slightly inferior to the optic nerve, then usually crosses superior to the optic nerve, and proceeds anteriorly on the medial side of the orbit, a° After the ophthalmic artery was identified on the medial side of the optic nerve approx-
Hata, Hata, and Moritake
175
imately 15 mm from the disk with color Doppler flow imaging, velocity waveforms were recorded over five cardiac cycles with pulsed Doppler ultrasonography with a 5 MHz microconvex transducer (Aloka SSD2000, Tokyo). In the color Doppler mode the flow directed toward the transducer was displayed in shades of red and the flow directed away from the transducer was in shades of blue. In the color and pulsed Doppler modes the lowest possible measurable velocity was 1.54 cm per second. Pulse repetition frequencies were 125 kHz, the maximum penetration depth was 12 cm, and the gate width used in this study was 3 mm. Wall filters (50 Hz) eliminated low-frequency signals occurring from vesselwall motion. An angle correction indicator was used to ensure an angle of insonation of the ophthalmic artery of <20 degrees during spectral analysis. The frequency shift was corrected for angle. Peak systolic velocities, enddiastolic velocities, time-averaged mean peak velocities, and pulsatility index (Pulsatility index = (Peak systolic velocity - End-diastolic velocity)/Time-averaged mean peak velocity) were averaged for each side. For statistical analysis, the mean pulsatility index was evaluated by averaging the values obtained from the right and left sides. Statistical analysis for comparison of these data among the groups was done with analysis of variance and the Newman-Keuls multiple comparison test2 A value of p < 0.05 was considered significant. The correlation between the mean arterial blood pressure (MAP) and the ophthalmic artery pulsatility index was analyzed by curvilinear regression.
Results The MAP values in severe preeclampsia or chronic hypertension was higher than those values in other groups (p < 0.05) (Table I). The MAP value in mild preeclampsia or transient hypertension was higher than that in normotensive n o n p r e g n a n t women or normotensive pregnant women (p < 0.05). There was no significant difference in MAP between normotensive nonpregn a n t women and normotensive pregnant women, those with mild preeclampsia or transient hypertension, or those with severe preeclampsia or chronic hypertension. As described previously,8 there was also no change in the pulsatility index associated with gestational age in normotensive pregnant women i n this study. The pulsatility index in severe preeclampsia was lowest among the groups (p < 0.05), whereas that in normotensive pregnant women was highest among the groups (p < 0.05) (Table I and F i g . 1). The pulsatility index in mild preeclampsia was significantly lower than that in transient hypertension (p < 0.05). There was no significant difference in the pulsatility index between mild preeclampsia and chronic hypertension or between transient hypertension and chronic hypertension. The pulsa-
176 Hata, Hata, and Moritake
July 1997 Am J Obstet Gynecol
.
4"
m
3
,~.
2
E
=.
a==
-i-
Normotensive nonpregnant
Normotensive pregnant
Mild preeclampsia
Severe preeclampsia
Transient hypertension
Chronic hypertension
Fig. 1. Ophthalmic artery pulsatility index in each hypertensive group. Horizontal bars, Mean pulsatility index value in each group. Table I. Mean b l o o d pressure and o p h t h a l m i c artery pulsatility index in each g r o u p Normotensive nonpregnant (n = 17) MAP (mm Hg)
OAPI
83 ± 8*,t,++,§
2.55 -+ 0.27",t,+,§,11 ,
Normolensive pregnant (n = 29)
Mild preeclampsia (n = 9)
79 _+ 911,¶,#,** 2.92 ± 0.59*,¶,#,**,tt
111 _ 9*,ll,tt,++,+
130 ± 7t,¶,tt,§§
1.47 + 0.30t,¶,++,§§
+#++ 1.17 ± 0 .08+, ,++,1111,¶¶
Severe preeclampsia (n =6)
OAPI, Ophthalmic artery pulsatility index.
*p < tP < Sp < §p < liP < ¶p < #p <
0.05. 0.05. 0.05. 0.05. 0.05. 0.05. 0.05.
**p < 0.05. ttP < 0.05. ,++*p< 0.05.
§§p < 0.05. III[P< 0.05. ¶¶p < 0.05.
tility i n d e x inversely correlated well with the MAP ( R 2 = 0.645, p < 0.0001) (Fig. 2).
Comment We previously r e p o r t e d that a decrease in orbital vascular resistance and an increase in orbital perfusion were evident in mild preeclampsia, a, 9 In this investigation the pulsatility index in severe preeclampsia was significantly lower than that in mild preeclampsia. This indicates that a decrease in orbital vascular resistance and an increase in orbital perfusion are m u c h stronger in severe preeclampsia than in mild preeclampsia. Easterling and Benedetti n p r o p o s e d that the effects of hyperperfusion are n o t limited to the brain and e x t e n d to systemic organs. These data support the c o n c e p t that
preeclampsia is a hyperdynamic condition in which the characteristic hypertension and proteinuria are mediated by renal hyperperfusion. T h e p r o p o s e d m o d e l of preeclampsia suggests a hyperdynamic disease in which increased cardiac o u t p u t and compensatory vasodilation mediate end-organ damage. If this m o d e l is to be consistent with clinical observations, h e m o d y n a m i c alterations must in some way lead to proteinuria and hypertension. These authors 11 also hypothesized that the hyperdynamic condition is associated with vasodilation of the g l o m e r u l a r afferent arteriole, which exposes capillaries to increased flow and mediates the d e v e l o p m e n t of hypertension and proteinuria. Kuo et al. 12 r e p o r t e d a decreased vascular resistance in maternal renal artery blood flow velocity waveforms in patients with mild
Volume 177, Number I AmJ Obstet Gynecol
Hata, Hata, and Moritake
140
e°
y = 173.06 - 48.380x + 5.7103x^2 •
•
177
R^2 = 0.645
0 °0
120
rgl
'-
100
o @
• o
;.¢:
80
60 0
I
1
I
I
I
1
2
3
4
5
Ophthalmic artery pulsatility index Fig. 2. Correlation between ophthalmic artery pulsatility index and mean blood pressure.
Transient hypertension (n= 6)
Chronic hypertension (n= 9)
109 -+ 4+,#,§§,HH 1.89 _+0.27§,**,§§,]111
122 + 8§,**,++++,HH 1.69 _+o.4911,tt,¶¶
preeclampsia. Zunker et al.13 described that the low pulsatility index in intracranial arterial blood flow velocities in patients with the preeclampsia-eclampsia syndrome suggests a forced vasodilation, probably resulting from passive overdistention of cerebral arterioles and vasogenic edema. These findings support the concept of forced vasodilation as a pathogenic key event associated with the preeclampsia. Furthermore, our study showed more severe hyperperfusion of orbital circulation in severe preeclampsia than in mild preeclampsia. This might explain the severe clinical manifestations, probably the result of severe hyperperfusion, in severe preeclampsia. On the other hand, vasodilation is a normal response to increased blood pressure. The body will vasodilate if blood pressure exceeds the set point. When hypertension is driven by high cardiac output, compensatory vasodilation is an active compensatory mechanism. This seems to be a more likely mechanism when low resistance is found in mild preeclampsia. Cerebral blood flow autoregulation normally operates
between MAPs of 60 to 150 mm Hg. 14 In this study all patients showed MAP in the range of 60 to 140 mm Hg, and a good inverse correlation between maternal MAP and ophthalmic artery pulsatility index was noted. This result support the idea that cerebral blood flow autoregulation operates well u n d e r the MAP of 150 mm Hg during pregnancy. Under these conditions, the yascular smooth muscle cells may reach the limit of strength and then yield? 3 Although short segments overdistended first, the whole length of the vessel will finally be affected. Beyond the upper limit of MAP, hypertensive encephalopathy may occur. In this study the pulsatility index in normotensive pregnant women is higher than in normotensive nonpregnant women. The reason for the pulsatility index in pregnancy being higher than in the n o n p r e g n a n t state is currently unknown. Although there is no significant difference in MAP between these two groups, the MAP in normotensive pregnant women is low. Therefore one possible explanation for this difference is that cerebral blood flow autoregulation may operate in normotensive pregnant women because a good inverse correlation between the MAP and the ophthalmic artery pulsatility index is evident in our study. However, in view of the relatively small n u m b e r of subjects, further study is needed to clarify this difference in ophthalmic artery pulsatility index between normotensive n o n p r e g n a n t and pregnant women. There have been a few reports on the assessment of cerebral and orbital circulations with Doppler ultrasonography in the preeclampsia-eclampsia syndrome,s, 9.13 However, there has been no report on the evaluation of orbital circulation with color Doppler flow imaging in
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o t h e r hypertensive disorders during pregnancy. To the best of our knowledge, this is the first r e p o r t of orbital circulatory changes in o t h e r hypertensive disorders during pregnancy. Consequently, the pulsatility i n d e x value in transient hypertension or chronic hypertension was significantly lower than that in normotensive p r e g n a n t w o m e n but was significantly h i g h e r than in mild preeclampsia. T h e r e f o r e mild hyperperfusion in the orbital circulation was n o t e d in patients with transient hypertension or chronic hypertension d u r i n g pregnancy. T h e reason for these differences of the o p h t h a l m i c artery flow velocity waveforms between preeclampsia and o t h e r hypertensive disorders during p r e g n a n c y is currently unknown. O n e possible explanation is that the degree of vasodilation of cerebral arteries and the duration of disease process might be different between theses disorders. Further study is n e e d e d to clarify the m e c h a n i s m of cerebral circulatory h e m o d y n a m i c s in pregnancies complicated by hypertensive disorders. REFERENCES
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3. Gant NF, Worley RJ. Hypertension in pregnancy: concepts and management. New York: Appleton-Century-Crofts; 1980. 4. Lindheimer MD, Katz M. Hypertension and pregnancy. In: Genest J, Kuchel O, Pavel H, Cantin M, editors. Hypertension. 2nd ed. New York: McGraw-Hill; 1983. p. 889-913. 5. Ferris TE: How should hypertension during pregnancy be managed: an internist's approach. Med Clin North Am 1984;68:491-503. 6. Cunningham FG, Pritchard JA. How should hypertension during pregnancy be managed: experience at Parkland Memorial Hospital. Med Clin North Am 1984;68:505-26. 7. Jaffe G, Schatz H. Ocular manifestations of preeclampsia. A m J Ophthalmol 1987;103:309-15. 8. Hata T, Senoh D, Hata K, Kitao M. Ophthalmic artery velocimetry in pregnant women. Lancet 1992;340:182-3. 9. Hata T, Senoh D, Ha~a K, Kitao M. Ophthalmic artery velocimetry in preeclampsia. Gynecol Obstet Invest 1995;40: 32-5. 10. Erickson SJ, Hendrix LE, Massaro BM, Harris GJ, Lewandowski MF, Foley WD, et al. Color Doppler flow imaging of the normal and abnormal orbit. Radiology 1989;173:511-6. 11. Easterling TR, Benedetti TJ. Preeclampsia: a hyperdynamic disease model. Am J Obstet Gyneeol 1989;160:1447-53. 12. Kuo DM, Chiu TH, Hsieh TT. Maternal renal artery Doppler flow-velocity waveform in preeclampsia: a preliminary report. J Reprod Med 1993;38:189-92. 13. Zunker P, Ley-PozoJ, Louwen F, Sehuierer G, Holzgreve W, Ringelstein EB. Cerebral hemodynamics in pre-eclampsia/ eclampsia syndrome. Ultrasound Obstet Gynecol 1995;6: 411-5. 14. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990;2:161-92.