This Article Abstract Full Text (PDF) All Versions of this Article: 110/15/2241    most recent 01.CIR.0000144472.08647.40v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Immink, R. V. Articles by van Lieshout, J. J. Search for Related Content PubMed PubMed Citation Articles by Immink, R. V. Articles by van Lieshout, J. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines High Blood Pressure Hazardous Substances DB HYDROCORTISONE Related Collections Cerebrovascular disease/stroke Other hypertension Clinical Studies Other Treatment Doppler ultrasound, Transcranial Doppler etc.

(Circulation. 2004;110:2241-2245.)
© 2004 American Heart Association, Inc.

Vascular Medicine

Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

Rogier V. Immink, MD; Bert-Jan H. van den Born, MD; Gert A. van Montfrans, MD, PhD; Richard P. Koopmans, MD, PhD; John M. Karemaker, PhD; Johannes J. van Lieshout, MD, PhD

From the Departments of Physiology (R.V.I., J.M.K.), Internal Medicine (B.-J.H.v.d.B., G.A.v.M., J.J.v.L.), and Pharmacology and Pharmacotherapy (R.P.K.), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Correspondence to Johannes J. van Lieshout, MD, PhD, Department of Internal Medicine, Room F7-205, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail j.j.vanlieshout{at}amc.uva.nl

Received May 24, 2004; revision received July 29, 2004; accepted August 3, 2004.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— In patients with a malignant hypertension, immediate parenteral treatment with blood pressure–lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients.

Methods and Results— In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V_mean to MAP phase lead and static CA as the MCA V_mean to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V_mean to MAP phase lead was lower (30±8° versus 58±5°, mean±SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA V_mean decrease was 22±4%, along with a 27±3% reduction in MAP (from 166±4 to 121±6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82±0.15% cm · s^–1 · % mm Hg^–1; r=0.70±0.07).

Conclusions— In patients with malignant hypertension, dynamic CA is impaired. An MCA V_mean plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA V_mean decreases almost one on one with MAP.

Key Words: blood flow velocity • cerebrovascular circulation • hypertension • ultrasonics

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
In patients with malignant hypertension, immediate treatment with blood pressure (BP)–reducing agents such as intravenous sodium nitroprusside (SNP) or labetalol is indicated to limit cerebral, myocardial, and renal damage.¹ In these patients with a mean arterial pressure (MAP) >140 mm Hg, the presence of grade III to IV retinopathy and occasionally hypertensive encephalopathy, reflecting cerebral hyperperfusion and edema, is considered to indicate compromised cerebral autoregulatory capacity.^2,3 From this assumption, it has become generally accepted that the initial reduction in BP should not exceed 25% of the presenting level within the first hours of treatment to prevent cerebral hypoperfusion.^1,3–6

Cerebral autoregulation (CA) is defined as the intrinsic capacity of cerebral vasculature to maintain constant cerebral blood flow (CBF).^7–9 In normotensive subjects, when MAP decreases below 60 mm Hg, considered the lower limit of CA, CBF decreases proportionally with BP. Most patients suffering from malignant hypertension have a history of chronic hypertension,¹⁰ and in those patients, the lower limit of CA has been shifted in proportion toward higher pressures.^11,12 For obvious reasons, the upper limit of CA has not been determined in normotensive or hypertensive humans. It was located between 120 and 150 mm Hg¹³ in normotensive baboons and between 155 and 170 mm Hg in chronic hypertensive baboons.¹⁴

A moderate reduction in BP with SNP in normotensive subjects does not influence CBF,¹⁵ but to the best of our knowledge, no human studies specifically tested the assumption that CA is impaired in patients with malignant hypertension. Therefore, we determined CA in this group of patients before and during a decline in BP elicited by SNP.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Subjects
Eight consecutive patients fulfilling the World Health Organization criteria for malignant hypertension, namely severely elevated blood pressure plus grade III (bilateral retinal hemorrhages or cotton wool exudates; n=5) or IV (III plus papilledema; n=3) hypertensive retinopathy according to the Keith, Wagener, and Barker classification, were included in the study (Table 1).

View this table: [in this window] [in a new window]   TABLE 1. Characteristics of Reference Subjects and Patients

Before hospital admission, 3 of these 8 patients were known to have had moderate hypertension treated with 1 or 2 antihypertensive drugs. Two of these 3 patients withdrew medication without consulting their general practitioners. One had untreated hypertension, 1 was normotensive, and the other 3 had undocumented BP.

At hospital admission, 3 of 8 patients presented with symptoms of hypertensive encephalopathy (eg, convulsions before hospital admission). Six patients had left ventricular hypertrophy, 6 had moderately elevated plasma creatinine levels (between 100 and 200 µmol · L^–1), and 1 had considerably elevated (1050 µmol · L^–1) plasma creatinine level. A cause of hypertension was identified in 3 patients: high-dose corticosteroid treatment, a cortisol-producing adrenal carcinoma, and deterioration of renal function with volume overload related to IgA nephropathy. In 5 patients, extended testing, including renal artery imaging, did not identify a definite cause of the hypertension.

To decrease BP, intravenous SNP infusion was started at 0.3 µg · kg^–1 · min^–1. After 5 minutes, it was increased to 0.5 µg · kg^–1 · min^–1 and, from then on, by 0.5 µg · kg^–1 · min^–1 every 5 minutes until MAP had stabilized at 25% below the presenting value. Eight normotensive healthy subjects matched for age, weight, and height (Table 1) were included to estimate normal CA parameters.

In the first 6 months of follow-up, the patient with corticosteroids-related malignant hypertension was well controlled (BP, 110/80 mm Hg) with 2 antihypertensive drugs and tapering of corticosteroid dosage. Four patients were well controlled (BP <140/90 mm Hg) with 3 or 4 antihypertensive drugs. In 2 others, BP was moderately elevated (BP, 150/90 mm Hg and 160/100 mm Hg) despite the use of 3 and 5 drugs, respectively.

All subjects, or a direct relative in case of encephalopathy, received verbal and written explanation of the objectives and techniques of measurements and risks and benefits associated with the study. They provided written informed consent in accordance with the Helsinki Declaration. This study was approved by the Medical Ethics Committee of the Academic Medical Center, University of Amsterdam (the Netherlands; MEC 02/194).

Measurements
Patients and reference subjects were instrumented with ECG electrodes while in the supine position. In the patients, intra-arterial pressure (IAP) was monitored through a catheter (1.1-mm ID, 20 gauge) placed in the radial artery of the nondominant arm. For comparison between patients and reference subjects, finger BP (FinAP) was measured by photoelectric plethysmography (Portapres; Netherlands Organization for Applied Scientific Research, Biomedical Instrumentation, TNO-BMI) in both groups. Changes in FinAP accurately track changes in IAP during normotension,^16–18 and this study confirms this observation in extreme hypertension. The cuff was applied to the middle finger of the dominant hand placed at heart level. Stroke volume (SV) was determined by a 3-element model of arterial input impedance (Modelflow).¹⁹ Modelflow computes a flow wave from the FinAP wave that is integrated to obtain the SV of the heart.

When calibrated against a "gold standard" method to determine cardiac output (CO) such as thermodilution or the Fick method, this methodology provides accurate estimates of changes in SV in patients with septic shock²⁰ and cardiovascular disease^19,21 and during orthostatic stress.²² The middle cerebral artery blood velocity (MCA V) was measured in the proximal segment of the right MCA (Multidop X4). Once the optimal signal-to-noise ratio was obtained, the probe was secured with a headband (Mark 600, Spencer Technologies). SNP was administered with a perfusor (B. Braun Medical Inc).

Data Analysis
The signals of IAP, FinAP, spectral envelope of MCA V, and a marker signal were A/D converted at 100 Hz and stored on a hard disk for offline analysis. In the patients, all signals were monitored from 20 minutes before SNP infusion to 1 hour after the last increment of SNP dose. Measurements were obtained in the reference subjects in the supine position for 30 minutes. Mean MCA V (MCA V_mean), mean IAP, and mean FinAP were integral over 1 heartbeat. Heart rate (HR) was the inverse of the interbeat pressure interval; cardiac output (CO) was the product of SV and HR; and systemic vascular resistance (SVR) was mean IAP divided by CO. Because Modelflow was not calibrated, SV, CO, and SVR were expressed as percentage of the presenting value. To assess the effect of SNP on cerebrovascular conductance, a cerebrovascular conductance index was calculated as MCA V_mean divided by mean IAP.¹⁸ Changes in systemic and cerebral hemodynamics elicited by SNP were expressed as averages of 3-minute episodes of mean IAP, HR, SV, CO, SVR, MCA V_mean, and cerebrovascular conductance index determined at 3 moments: before SNP treatment, midway through treatment, and when target BP was reached.

For maintaining CBF, both fast- and slow-acting regulatory mechanisms are required to span the prevailing demands on CBF in everyday life.²³

Static CA (sCA) reflects overall efficiency of the autoregulation system and is assessed by monitoring the CBF during different levels of BP. Because changes in CBF are tracked by changes in MCA V_mean,²⁴ sCA is considered intact when MCA V_mean barely changes during a decrease in IAP. To assess sCA for individual subjects in this study, the continuous signals of MCA V_mean and IAP were first averaged to 30-second episodes and then linearly related to each other.

Dynamic CA (dCA) refers to the ability to restore CBF in the face of a sudden change in perfusion pressure and reflects the latency of the system.²⁵ It is quantified by the counterregulatory capacity to maintain constant MCA V during an induced or spontaneous abrupt changes in BP. In healthy subjects, MCA V_mean leads MAP with 2.5 seconds in the time domain²⁵ and 60° in the frequency domain around the 0.1-Hz spontaneous BP variability.²⁶ In this study, dCA was determined in the frequency domain from 3-minute episodes of beat-to-beat data of mean FinAP and MCA V_mean before SNP treatment and after target BP was reached. These data were compared with dCA in reference subjects determined in the supine resting state. To quantify the variability of pressure and velocity, power spectra were computed for mean FinAP and MCA V_mean with discrete Fourier transform after spline interpolation and resampling at 4 Hz of the beat-to-beat data sets. Results were expressed as the integrated area in the low-frequency range (0.07 to 0.15 Hz). To examine the strength between low-frequency mean FinAP and MCA V_mean, coherence was used to signify that the 2 cardiovascular signals covary significantly at a given frequency. The squared coherence function reflects the fraction of output power (MCA V_mean) that can be linearly related to the input power (mean FinAP) at each frequency. Like a correlation coefficient, it varies between 0 and 1. From the mean FinAP to MCA V_mean cross spectrum, the transfer function gain (cm · s^–1 · mm Hg^–1) and the MCA V_mean to mean FinAP phase lead (degrees) were obtained in the low-frequency area.²⁷ The transfer function gain was normalized for mean FinAP and MCA V_mean to account for the intersubject variability and expressed as percent change in cm · s^–1 per percent change in mm Hg.²⁸ Phase was defined as positive when MCA V_mean leads mean FinAP.

Statistical Analysis
Data are expressed as mean and range in tables and as mean±SEM in figures. Changes in systemic and cerebral hemodynamics during SNP treatment were examined by Friedman ANOVA on ranks. sCA was analyzed by nonparametric regression technique (Spearman rank order). Differences in dCA between reference subjects and hypertensive patients (unpaired) and before and after treatment (paired) were examined with the Wilcoxon rank-sum test and the Wilcoxon signed-rank test, respectively. A value of P<0.05 was considered to indicate a statically significant difference.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Characteristics of Patients and Reference Subjects
Patients did not differ from normotensive reference subjects in age, height, and weight. BP and HR at admission were higher in the patient group (P<0.01), although MCA V was comparable (Table 1).

CA Before Treatment
Low-frequency variability of mean FinAP and MCA V_mean were comparable for patients and reference subjects with a smaller phase lead (P<0.05) and a tendency toward a higher transfer gain in the patients (Table 2).

View this table: [in this window] [in a new window]   TABLE 2. dCA in Reference Subjects and Patients

CA During Treatment
Target mean IAP was reached within 90 minutes in all patients (Figure 1). With increasing dose of SNP, SVR declined (–43±5%), whereas HR (16±4 bpm), SV (9±4%), and thus CO (31±8%) increased (Figure 2). Systolic IAP decreased from 225±8 to 182±6 mm Hg; mean IAP, from 166±4 to 122±6 mm Hg, and diastolic IAP, from 137±6 to 102±6 mm Hg. The cerebrovascular conductance index did not increase significantly (9.5±5.3%).

View larger version (9K): [in this window] [in a new window]   Figure 1. BP response to SNP. Averaged decrease in mean IAP during SNP treatment of 8 subjects with malignant hypertension. Values are mean±SEM.

View larger version (19K): [in this window] [in a new window]   Figure 2. Systemic and cerebral hemodynamic responses to SNP. Averaged changes in HR, SV, CO, and SVR of 8 subjects with malignant hypertension during decrease in mean IAP induced by SNP. Values are mean±SEM. All parameters differ significantly from starting values.

MCA V_mean decreased 22±4%, along with a 27±3% reduction in MAP in a linear fashion (averaged slope, 0.82±0.15; averaged r=0.70±0.07; Figures 3 and 4). With mean IAP stabilized, variability of mean FinAP and MCA V_mean and the MCA V_mean to mean FinAP phase lead and transfer gain were not significantly different from values before SNP treatment or from reference subjects (Table 2).

View larger version (15K): [in this window] [in a new window]   Figure 3. Representative example of sCA. Representative example of decrease in MCA Vmean during decrease in mean IAP induced by SNP in patient with malignant hypertension. Circles represent average of 30 seconds. Regression coefficient of this patient is as follows: MCA Vmean=0.81xIAP+19.7; r=0.87.

View larger version (9K): [in this window] [in a new window]   Figure 4. sCA. Averaged decrease in MCA Vmean during decrease in mean IAP as induced by SNP in 8 patients with malignant hypertension. Values are mean±SEM.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The main findings of this study are that both dCA and sCA are impaired in patients with malignant hypertension before and during treatment with SNP. The data of this study show that during a rapid reduction in BP with SNP, MCA V_mean decreases almost one on one with MAP.

Study Limitations
The technique to monitor changes in arterial CBF may raise discussion for several reasons. First, MCA V_mean is calculated from the frequency distribution of the Doppler shifts, and it is assumed to represent flow velocity in the center of the vessel. Changes in MCA V_mean, however, reflect changes in flow²⁴ only when the diameter of the MCA remains constant during SNP treatment. Direct observations made during craniotomy have revealed that SNP did not affect the vessel diameter of the M1 segment of the MCA²⁹; therefore, we consider that changes in MCA V_mean in this study are proportional to those in flow.

Second, it is uncertain at which level of MAP the upper and lower limits of sCA are located in patients (admitted to hospital) with malignant hypertension. In normotensive humans, the lower limit of sCA is located 60 mm Hg.^12,30,31 For obvious reasons, the upper limit of sCA cannot be studied in (normotensive) humans, but in normotensive baboons, it ranges between 120 and 150 mm Hg.¹³ In humans with untreated severe chronic hypertension, the lower limit of sCA is shifted rightward to 115 mm Hg.^11,12 Data on the upper limit of sCA are limited in that it was determined in only 3 hypertensive baboons and was found to be shifted rightward (between 155 and 169 mm Hg).¹⁴ We assume, with MAP 165 mm Hg at admission in this study, that the pressure level was located around the upper limit of sCA with dCA impaired before treatment with SNP. The finding that, during treatment with IAP in the autoregulatory range, MCA V_mean decreased almost one on one with MAP conforms with impaired CA.

Third, in the reference subjects, we did not determine MCA V during a substantial decrease in BP induced by SNP infusion; thus, sCA was not evaluated. We consider that, in healthy subjects, a decline in MAP induced by SNP of 20% barely affects MCA V_mean,³² and CBF,¹⁵ whereas a reduction in mean IAP in the patients was associated with a significant decline in MCA V_mean. In addition, in healthy subjects, data on dCA reflect the integrity of sCA³³, and we assume sCA to be preserved in the reference subjects.

sCA and dCA
Autoregulation implies that blood flow is maintained at a normal level of 60 mL/ 100 g brain tissue per minute despite changes in perfusion pressure.⁷ Impaired sCA, with loss of the more-or-less zero-slope MAP–MCA V_mean relationship, has been reported in ischemic stroke,³⁴ in severe head injury,³⁵ and after cardiac arrest.³⁶ Our findings suggest that sCA also is impaired in patients with malignant hypertension.

dCA is quantified by the counterregulatory capacity to maintain MCA V during abrupt changes in BP induced by thigh cuff deflation²⁵ or as evaluated by the transfer gain and phase lead of MCA V_mean to MAP during imposed³⁷ or spontaneous BP oscillations.^38,39 During both hypotension⁸ and hypertension,²⁶ this phase lead remains unaltered compared with the normal situation. In the present study, the MCA V_mean to MAP phase lead in patients with malignant hypertension before SNP treatment was significantly smaller than in the reference subjects and comparable to the phase lead found in patients with carotid artery obstruction.³⁷ The tendency toward a larger transfer gain further supports a deteriorated dampening of BP oscillations in patients with malignant hypertension.

SNP and Cerebral Hemodynamics
Kety et al⁴⁰ observed that, in chronically hypertensive patients, global resting CBF and cerebral oxygen consumption are not different from those in normotensive subjects but that cerebrovascular resistance is elevated. SNP reduces SVR, but when infused directly in the carotid artery, it does not modify cerebrovascular resistance in healthy subjects.⁴¹ These findings, together with recent evidence that in normotensive subjects a reduction in MAP by SNP does not affect MCA V_mean,³² suggest that when BP is reduced pharmacologically, MCA V is secured by CA-mediated cerebral vasodilatation rather than a direct SNP-induced pharmacological effect on the cerebral vasculature. The present data demonstrate systemic vasodilatation during SNP treatment with a considerable increase in CO but no change in the cerebrovascular conductance index. One may speculate that the linear relation between MAP and MCA V_mean during treatment with SNP reflects a preferential blood flow to the (low-resistance) systemic vascular bed versus the (high-resistance) cerebrovascular bed.

In conclusion, in patients with malignant hypertension, dCA is impaired. Decreases in cerebral artery blood velocity and BP in a linear fashion during SNP treatment also indicate impairment of sCA. This study confirms the contention that CA is compromised in patients with malignant hypertension.

	Acknowledgments

 
This study was sponsored in part by grant 98.172 from the Dutch Heart Foundation.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997; 157: 2413–2446.[Abstract/Free Full Text]

2. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996; 334: 494–500.[Abstract/Free Full Text]

3. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet. 2000; 356: 411–417.[CrossRef][Medline] [Order article via Infotrieve]

4. Ledingham JG, Rajagopalan B. Cerebral complications in the treatment of accelerated hypertension. Q J Med. 1979; 48: 25–41.[Medline] [Order article via Infotrieve]

5. Haas DC, Streeten DH, Kim RC, et al. Death from cerebral hypoperfusion during nitroprusside treatment of acute angiotensin-dependent hypertension. Am J Med. 1983; 75: 1071–1076.[CrossRef][Medline] [Order article via Infotrieve]

6. Kaplan NM. Hypertensive crises. In: Kaplan NM, ed. Clinical Hypertension. Baltimore, Md: Williams & Wilkins; 1998: 265–280.

7. Lassen NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959; 39: 183–238.[Free Full Text]

8. Schondorf R, Stein R, Roberts R, et al. Dynamic cerebral autoregulation is preserved in neurally mediated syncope. J Appl Physiol. 2001; 91: 2493–2502.[Abstract/Free Full Text]

9. Van Lieshout JJ, Wieling W, Karemaker JM, et al. Syncope, cerebral perfusion, and oxygenation. J Appl Physiol. 2003; 94: 833–848.[Abstract/Free Full Text]

10. Zampaglione B, Pascale C, Marchisio M, et al. Hypertensive urgencies and emergencies: prevalence and clinical presentation. Hypertension. 1996; 27: 144–147.[Abstract/Free Full Text]

11. Strandgaard S. Autoregulation of cerebral blood flow in hypertensive patients: the modifying influence of prolonged antihypertensive treatment on the tolerance to acute, drug-induced hypotension. Circulation. 1976; 53: 720–727.[Abstract/Free Full Text]

12. Schmidt JF, Waldemar G, Vorstrup S, et al. Computerized analysis of cerebral blood flow autoregulation in humans: validation of a method for pharmacologic studies. J Cardiovasc Pharmacol. 1990; 15: 983–988.[Medline] [Order article via Infotrieve]

13. Strandgaard S, MacKenzie ET, Sengupta D, et al. Upper limit of autoregulation of cerebral blood flow in the baboon. Circ Res. 1974; 34: 435–440.[Abstract/Free Full Text]

14. Strandgaard S, Jones JV, MacKenzie ET, et al. Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res. 1975; 37: 164–167.[Abstract/Free Full Text]

15. Henriksen L, Paulson OB. The effects of sodium nitroprusside on cerebral blood flow and cerebral venous blood gases, II: observations in awake man during successive blood pressure reduction. Eur J Clin Invest. 1982; 12: 389–393.[Medline] [Order article via Infotrieve]

16. Friedman DB, Jensen FB, Matzen S, et al. Non-invasive blood pressure monitoring during head-up tilt using the Penaz principle. Acta Anaesthesiol Scand. 1990; 34: 519–522.[Medline] [Order article via Infotrieve]

17. Eckert S, Horstkotte D. Comparison of Portapres non-invasive blood pressure measurement in the finger with intra-aortic pressure measurement during incremental bicycle exercise. Blood Press Monit. 2002; 7: 179–183.[CrossRef][Medline] [Order article via Infotrieve]

18. Zhang R, Crandall CG, Levine BD. Cerebral hemodynamics during the Valsalva maneuver: insights from ganglionic blockade. Stroke. 2004; 35: 843–847.[Abstract/Free Full Text]

19. Wesseling KH, Jansen JRC, Settels JJ, et al. Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol. 1993; 74: 2566–2573.[Abstract/Free Full Text]

20. Jellema WT, Wesseling KH, Groeneveld AB, et al. Continuous cardiac output in septic shock by simulating a model of the aortic input impedance: a comparison with bolus injection thermodilution. Anesthesiology. 1999; 90: 1317–1328.[CrossRef][Medline] [Order article via Infotrieve]

21. Jansen JRC, Schreuder JJ, Mulier JP, et al. A comparison of cardiac output derived from the arterial pressure wave against thermodilution in cardiac surgery patients. Br J Anaesth. 2001; 87: 212–222.[Abstract/Free Full Text]

22. Harms MPM, Wesseling KH, Pott F, et al. Continuous stroke volume monitoring by modeling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress. Clin Sci. 1999; 97: 291–301.[Medline] [Order article via Infotrieve]

23. Aaslid R. Cerebral hemodynamics. In: Newell DW, Aaslid R, eds. Transcranial Doppler. New York, NY: Raven Press, Ltd; 1992: 49–55.

24. Bishop CC, Powell S, Rutt D, et al. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke. 1986; 17: 913–915.[Abstract/Free Full Text]

25. Aaslid R, Lindegaard KF, Sorteberg W, et al. Cerebral autoregulation dynamics in humans. Stroke. 1989; 20: 45–52.[Abstract/Free Full Text]

26. Lipsitz LA, Mukai S, Hamner J, et al. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke. 2000; 31: 1897–1903.[Abstract/Free Full Text]

27. Zhang R, Zuckerman JH, Levine BD. Deterioration of cerebral autoregulation during orthostatic stress. J Appl Physiol. 1998; 85: 1113–1122.[Abstract/Free Full Text]

28. Panerai RB, Dawson SL, Potter JF. Linear and nonlinear analysis of human dynamic cerebral autoregulation. Am J Physiol Heart Circ Physiol. 1999; 277: H1089–H1099.[Abstract/Free Full Text]

29. Giller CA, Bowman G, Dyer H, et al. Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. Neurosurgery. 1993; 32: 737–741.[Medline] [Order article via Infotrieve]

30. Larsen FS, Olsen KS, Hansen BA, et al. Transcranial Doppler is valid for determination of the lower limit of cerebral blood flow autoregulation. Stroke. 1994; 25: 1985–1988.[Abstract]

31. Olsen KS, Svendsen LB, Larsen FS. Validation of transcranial near-infrared spectroscopy for evaluation of cerebral blood flow autoregulation. J Neurosurg Anesthesiol. 1996; 8: 280–285.[Medline] [Order article via Infotrieve]

32. Lavi S, Egbarya R, Lavi R, et al. Role of nitric oxide in the regulation of cerebral blood flow in humans: chemoregulation versus mechanoregulation. Circulation. 2003; 107: 1901–1905.[Abstract/Free Full Text]

33. Tiecks FP, Lam AM, Aaslid R, et al. Comparison of static and dynamic cerebral autoregulation measurements. Stroke. 1995; 26: 1014–1019.[Abstract/Free Full Text]

34. Schwarz S, Georgiadis D, Aschoff A, et al. Effects of induced hypertension on intracranial pressure and flow velocities of the middle cerebral arteries in patients with large hemispheric stroke. Stroke. 2002; 33: 998–1004.[Abstract/Free Full Text]

35. Czosnyka M, Smielewski P, Piechnik S, et al. Cerebral autoregulation following head injury. J Neurosurg. 2001; 95: 756–763.[CrossRef][Medline] [Order article via Infotrieve]

36. Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke. 2001; 32: 128–132.[Abstract/Free Full Text]

37. Diehl RR, Linden D, Lucke D, et al. Phase relationship between cerebral blood flow velocity and blood pressure: a clinical test of autoregulation. Stroke. 1995; 26: 1801–1804.[Abstract/Free Full Text]

38. Zhang R, Zuckerman JH, Giller CA, et al. Transfer function analysis of dynamic cerebral autoregulation in humans. Am J Physiol Heart Circ Physiol. 1998; 274: H233–H241.[Abstract/Free Full Text]

39. Panerai RB, Hudson V, Fan L, et al. Assessment of dynamic cerebral autoregulation based on spontaneous fluctuations in arterial blood pressure and intracranial pressure. Physiol Meas. 2002; 23: 59–72.[CrossRef][Medline] [Order article via Infotrieve]

40. Kety SS, Hafkenschiel JH, Jeffers WA, et al. The blood flow, vascular resistance and oxygen consumption of the brain in essential hypertension. J Clin Invest. 1948; 27: 511–514.[Medline] [Order article via Infotrieve]

41. Joshi S, Young WL, Duong H, et al. Intracarotid nitroprusside does not augment cerebral blood flow in human subjects. Anesthesiology. 2002; 96: 60–66.[CrossRef][Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				R. Zhang, K. Behbehani, and B. D. Levine Dynamic pressure\#8211;flow relationship of the cerebral circulation during acute increase in arterial pressure J. Physiol., June 1, 2009; 587(11): 2567 - 2577. [Abstract] [Full Text] [PDF]

				Y.-S. Kim, E. Nur, E. J. van Beers, J. Truijen, S. C.A.T. Davis, B. J. Biemond, and J. J. van Lieshout Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease Stroke, March 1, 2009; 40(3): 808 - 814. [Abstract] [Full Text] [PDF]

				J. A. H. R. Claassen, B. D. Levine, and R. Zhang Dynamic cerebral autoregulation during repeated squat-stand maneuvers J Appl Physiol, January 1, 2009; 106(1): 153 - 160. [Abstract] [Full Text] [PDF]

				R. V. Immink, B.-J. H. van den Born, G. A. van Montfrans, Y.-S. Kim, M. W. Hollmann, and J. J. van Lieshout Cerebral Hemodynamics During Treatment With Sodium Nitroprusside Versus Labetalol in Malignant Hypertension Hypertension, August 1, 2008; 52(2): 236 - 240. [Abstract] [Full Text] [PDF]

				S. Ogoh, R. M. Brothers, W. L. Eubank, and P. B. Raven Autonomic Neural Control of the Cerebral Vasculature: Acute Hypotension Stroke, July 1, 2008; 39(7): 1979 - 1987. [Abstract] [Full Text] [PDF]

				Y.-S. Kim, R. Krogh-Madsen, P. Rasmussen, P. Plomgaard, S. Ogoh, N. H. Secher, and J. J. van Lieshout Effects of hyperglycemia on the cerebrovascular response to rhythmic handgrip exercise Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H467 - H473. [Abstract] [Full Text] [PDF]

				S. Ruland and V. Aiyagari Cerebral Autoregulation and Blood Pressure Lowering Hypertension, May 1, 2007; 49(5): 977 - 978. [Full Text] [PDF]

				R. Zhang, S. Witkowski, Q. Fu, J. A.H.R. Claassen, and B. D. Levine Cerebral Hemodynamics After Short- and Long-Term Reduction in Blood Pressure in Mild and Moderate Hypertension Hypertension, May 1, 2007; 49(5): 1149 - 1155. [Abstract] [Full Text] [PDF]

				R. B. Panerai, P. J. Eames, and J. F. Potter Multiple coherence of cerebral blood flow velocity in humans Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H251 - H259. [Abstract] [Full Text] [PDF]

				T. K. Bergersen, T. W. Hartgill, and J. Pirhonen Cerebrovascular response to normal pregnancy: a longitudinal study Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1856 - H1861. [Abstract] [Full Text] [PDF]

				R. V. Immink, G. A. van Montfrans, J. Stam, J. M. Karemaker, M. Diamant, and J. J. van Lieshout Dynamic Cerebral Autoregulation in Acute Lacunar and Middle Cerebral Artery Territory Ischemic Stroke Stroke, December 1, 2005; 36(12): 2595 - 2600. [Abstract] [Full Text] [PDF]

				R. B. Panerai, M. Moody, P. J. Eames, and J. F. Potter Dynamic cerebral autoregulation during brain activation paradigms Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1202 - H1208. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 110/15/2241    most recent 01.CIR.0000144472.08647.40v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Immink, R. V. Articles by van Lieshout, J. J. Search for Related Content PubMed PubMed Citation Articles by Immink, R. V. Articles by van Lieshout, J. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines High Blood Pressure Hazardous Substances DB HYDROCORTISONE Related Collections Cerebrovascular disease/stroke Other hypertension Clinical Studies Other Treatment Doppler ultrasound, Transcranial Doppler etc.