Donate Help Contact The AHA Sign In Home
American Heart Association
Stroke
Search: search_blue_button Advanced Search
Stroke. 1996;27:1328-1332

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Izumi, Y.
Right arrow Articles by Matsuo, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Izumi, Y.
Right arrow Articles by Matsuo, H.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CARBON DIOXIDE

(Stroke. 1996;27:1328-1332.)
© 1996 American Heart Association, Inc.


Articles

Effects of Defibrination on Hemorheology, Cerebral Blood Flow Velocity, and CO2 Reactivity During Hypocapnia in Normal Subjects

Yoshinari Izumi, MD; Yoshiyasu Tsuda, MD; Shin-Ichiro Ichihara, MD; Tsutomu Takahashi, MD Hirohide Matsuo, MD

the Second Department of Internal Medicine, Kagawa (Japan) Medical School.

Correspondence to Yoshinari Izumi, MD, Second Department of Internal Medicine, Kagawa Medical School, 1750-1 Ikenobe, Miki-Cho, Kagawa, 761-07 Japan. E-mail izumi@kms.ac.jp.


*    Abstract
up arrowTop
*Abstract
down arrowIntroduction
down arrowSubjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Background and Purpose Plasma fibrinogen is reported to be an independent risk factor for stroke and cardiovascular diseases. The effects of defibrination on hemorheology, middle cerebral artery (MCA) blood flow velocity, and CO2 reactivity during hypocapnia were evaluated in normal subjects.

Methods Twenty-five healthy subjects (mean age, 31.8±5.7 years) were included in the study. Measurements were done at rest and repeated 24 hours after administration of 10 batroxobin units. Plasma fibrinogen, plasma viscosity, and whole blood viscosity were measured as hemorheological factors. MCA blood flow velocity was measured with a transcranial Doppler flowmeter. Blood flow velocity was corrected to 40 mm Hg of end-tidal CO2 partial pressure (PETCO2), and expressed as CV40. CO2 reactivity was measured as percent change in mean blood flow velocity per millimeter of mercury PETCO2.

Results Plasma fibrinogen (from 7.04 to 2.29 µmol/L; P<.001), whole blood viscosity, and plasma viscosity decreased after administration of batroxobin. Mean MCA blood flow velocity at rest, CV40, and CO2 reactivity during hypocapnia increased significantly (from 67.4 to 73.6 cm/s, from 71.7 to 77.7 cm/s, and from 2.9%/mm Hg to 3.2%/mm Hg, respectively; P<.01) after defibrination. Mean arterial blood pressure and PETCO2 at rest were constant before and 24 hours after administration of batroxobin. There was a significant positive correlation between CV40 and CO2 reactivity (r=.623, P<.0001).

Conclusions The increase in MCA blood flow velocity was associated with improved CO2 reactivity and reduced blood viscosity after defibrination. The data may suggest that defibrination increases cerebral blood flow by reducing blood viscosity.


Key Words: carbon dioxide • cerebral blood flow • fibrinogen • rheology • ultrasonics


*    Introduction
up arrowTop
up arrowAbstract
*Introduction
down arrowSubjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Recent studies have shown that plasma fibrinogen is an independent risk factor for stroke and ischemic heart disease.1 2 3 4 Since fibrinogen is highly viscous, elevated plasma fibrinogen levels increase blood viscosity. The increased shear stress due to high blood viscosity may injure the endotheliocyte of vessel walls and activate platelets, all of which may lead to further impairments of the cerebral microcirculation. With decreased plasma fibrinogen, on the other hand, reduced blood viscosity may accelerate CBF. Regarding the effects of rheological changes on CBF, several studies on the effect of hemodilution demonstrated an inverse correlation between the values of CBF and hematocrit.5 6 7 8 9 Blood viscosity may influence CBF if the perfusion pressure and vessel caliber are constant.10 Whether hemorheological improvements by blood defibrination influence CBF is a matter of debate. Batroxobin, a venom of Bothrops atrox (Tobishi Pharmaceutical Industries Co, Ltd), converts plasma fibrinogen to readily water-soluble fibrin microclots, which are eliminated as fibrin degradation products in the urine without significantly affecting the platelet count and other blood clotting factors.11 The objective of this study was to evaluate the effects of enzymatic blood defibrination on hemorheology, MCA blood flow velocity, and CO2 reactivity during hypocapnia in young adults who have a normal cerebral microcirculation before evaluating patients with cerebrovascular disease.


*    Subjects and Methods
up arrowTop
up arrowAbstract
up arrowIntroduction
*Subjects and Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Twenty-five healthy subjects (5 women, 20 men; mean age, 31.8±5.7 years) received batroxobin, a venom of B atrox, intravenously for 1 hour as 10 batroxobin units diluted in 100 mL saline. Measurements of rheological variables and blood flow velocity were performed before and 24 hours after administration of batroxobin, respectively, since the plasma fibrinogen concentrations reach a nadir 24 hours after administration of 5 to 10 batroxobin units.11 12 During all TCD procedures, PETCO2 was monitored and recorded continuously with an infrared gas analyzer (Respina, model 1H21A, NEC). Arterial blood pressure and heart rate were recorded simultaneously (model CBM-2000, NEC). tcPO2 was monitored noninvasively with an oxycapnomonitor (model SMK 365, Hellige) in 20 subjects. The values of PO2 measured by this monitor are reported to correlate with PaO2 under stable circulation.13 14

The subjects were informed of the procedures, and their consent was obtained for the study under the guidance of the ethical committee for clinical research of Kagawa Medical School.

Blood Viscosity Measurements
Whole blood viscosity at shear rates of 22.5 to 562.5 s-1, plasma viscosity, corrected blood viscosity at shear rates of 45 s-1 and 225 s-1, serum hematocrit, albumin, and plasma fibrinogen were measured before and 24 hours after administration of batroxobin. A cone-plate viscometer (Biorheolizer, BRL-1000) was used for the measurement of whole blood and plasma viscosity. The corrected blood viscosity for the standard hematocrit level of 45% ({eta}45) was calculated by the formula reported by Nicolaides et al15 :

where {eta} is whole blood viscosity and A is a constant at each shear rate. To determine hematocrit, a microhematocrit centrifuge method was used. ESR was measured as an index of erythrocyte aggregation, and the osmotic fragility of erythrocyte membrane was measured as an index of erythrocyte deformability with the use of a coil planet centrifuge (model ST, Sanki Engineering Ltd), which can be used for the evaluations of osmotic fragility of red blood cells.16

TCD Measurements
Mean MCA blood flow velocity and its CO2 reactivity were measured by TCD (TC2-64, Eden Medical Electronics Inc) according to the procedures described in previous studies17 18 19 20 at rest and during hypocapnia induced by hyperventilation for 1 minute. Each subject was placed in the supine position with both eyes closed. The 2-MHz pulsed Doppler probe was positioned in the temporal region (ultrasonic window), and an elastic bandage was used to avoid the shift of the probe during investigations. The highest signal was sought at a depth ranging from 45 to 55 mm. The mean flow velocity was calculated continuously as the time-averaged maximum velocity over the cardiac cycle computed from the envelope of the maximum frequencies. During continuous monitoring by a capnometer, the subject was instructed to breathe normally until a steady state was reached (PETCO2 values before and after administration of batroxobin were 38.6±4.2 and 38.8±4.6 mm Hg, respectively). The mean MCA blood flow velocity at rest was obtained in the stable normocapnic condition, and the point of the temporal window was marked for the repeated study afterward. The lowest mean flow velocity of the MCA near the end of the hyperventilation period was examined thereafter. Examinations were repeated during the same conditions 24 hours after administration. All TCD spectra were recorded onto a half-inch videotape for later reviews.

Since blood flow velocity is dependent on the PaCO2, we calculated the corrected blood flow velocity at 40 mm Hg of CO2 tension (CV40) according to the study of Markwalder et al19 :

where b is CO2 reactivity and V1 is velocity at P1CO2.

CO2 reactivity referred to the percent change in mean blood flow velocity per millimeter of mercury change in PETCO2, as calculated by the following formula:

where {Delta}PETCO2 is the change in PETCO2 from baseline to maximal hyperventilation.

Statistical comparisons between the values before and after administration of batroxobin were made with the paired t test, and P<.01 was considered significant. Data are expressed as mean±SD. Linear regression analysis and tests for the significance of differences between means of paired data were performed with a least squares method computed by a microcomputer and commercially available software packages.


*    Results
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowSubjects and Methods
*Results
down arrowDiscussion
down arrowReferences
 
Plasma fibrinogen concentration (from 7.04 to 2.29 µmol/L; P<.001), whole blood viscosity, and plasma viscosity decreased significantly 24 hours after administration of batroxobin (Table 1Down). Linear correlations were found between fibrinogen and the corrected blood viscosity at shear rates of 45 s-1 and 225 s-1 and between the values of fibrinogen and plasma viscosity (r=.421, P=.0023; r=.511, P=.0002; and r=.581, P<.0001, respectively). ESR decreased significantly, whereas hematocrit, albumin, and the osmotic fragility of erythrocyte membrane with coil planet centrifuge did not change significantly (Table 1Down). Mean MCA blood flow velocity at rest, corrected flow velocity, and CO2 reactivity during hypocapnia increased significantly (from 67.4 to 73.6 cm/s; from 71.7 to 77.7 cm/s; and from 2.9%/mm Hg to 3.2%/mm Hg, respectively; P<.01), whereas mean arterial blood pressure, heart rate, tcPO2, and PETCO2 at rest did not change significantly before and after administration of batroxobin (Table 2Down). Data regarding MCA blood flow velocity, corrected flow velocity, and CO2 reactivity in each subject compared with those before administration of batroxobin are shown in Figs 1 and 2DownDown.


View this table:
[in this window]
[in a new window]
 
Table 1. Hemorheological Variables Before and After Administration of Batroxobin in 25 Healthy Subjects


View this table:
[in this window]
[in a new window]
 
Table 2. Hemodynamics, Mean Blood Flow Velocity, Corrected Blood Flow Velocity (at PETCO2=40 mm Hg) and CO2 Reactivity Before and After Administration of Batroxobin in 25 Healthy Subjects



View larger version (21K):
[in this window]
[in a new window]
 
Figure 1. Mean MCA blood flow velocity at rest (a) and corrected blood flow velocity at PETCO2=40 mm Hg (b) before and after administration of batroxobin in 25 healthy subjects. P<.01 different from values before administration by paired t test.



View larger version (23K):
[in this window]
[in a new window]
 
Figure 2. CO2 reactivity to hypocapnia before and after administration of batroxobin in 25 healthy subjects. P<.01 different from values before administration by paired t test.

The correlation between the values of corrected blood flow velocity at PETCO2=40 mm Hg (CV40) and CO2 reactivity (n=50; 25 before and 25 after administration) is shown in Fig 3Down. The equation of the regression line for the relationship is CO2 reactivity=1.48±0.021·CV40 (r=.623), where CV40 and CO2 reactivity are expressed in units of centimeters per second and percent change per millimeter of mercury, respectively. There was a significant correlation, with a coefficient of .623 (P<.0001). However, the correlations between fibrinogen and CO2 reactivity or CV40 were not significant.



View larger version (20K):
[in this window]
[in a new window]
 
Figure 3. Relation between corrected blood flow velocity at PETCO2=40 mm Hg (CV40) and CO2 reactivity. Data before (n=25) and after (n=25) administration of batroxobin are shown. The equation of the regression line is CO2 Reactivity=1.481±0.021·CV40 (r=.623, P<.0001).


*    Discussion
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowSubjects and Methods
up arrowResults
*Discussion
down arrowReferences
 
Our results showed that mean MCA blood flow velocity, corrected blood flow velocity (at PETCO2=40 mm Hg), and CO2 reactivity increased significantly after defibrination. We used TCD for the direct measurement of CBF velocity. TCD measures blood flow velocity but not CBF. However, the changes in flow velocity may be proportional to those in CBF if the vessel diameter is constant. In humans, the diameter of a large cerebral artery with an internal diameter greater than 2.5 mm does not change significantly despite alternations in PaCO2.21 We investigated blood flow velocity in the proximal trunk of the MCA (depth of 45 to 55 mm from the skull) and assumed that the diameter of the MCA (3 to 5 mm in diameter22 ) would not change significantly before and after administration of batroxobin. Sorteberg et al23 reported a significant positive correlation between blood flow velocity in defined brain arteries and the corresponding regional CBF in resting normal subjects. The reproducibility of the TCD velocimetry is acceptable for repeated measurements of MCA blood flow velocity from one day to the next.24 25 Therefore, we regarded the change in MCA blood flow velocity as an index of CBF changes in the MCA territory.

Under normal physiological conditions, CBF is not affected by a moderate change in mean arterial blood pressure, ie, between 50 and 130 mm Hg.26 27 Mean blood flow velocity remains unaffected by the cardiac index in the range of 2.0 to 4.0 L/min per square meter.28 PaCO2 and arterial oxygen content can profoundly influence CBF and MCA blood flow velocity.29 30 31 We measured PETCO2 and tcPO2 instead of PaCO2 and PaO2, respectively. PETCO2 response curves for blood flow velocity in the MCA strongly resembled PaCO2 response curves for CBF.17 In adults, tcPO2 is 20% to 30% lower than PaO2 because of the properties of their skin32 ; however, they have shown a good correlation within the parameters of normal cardiac output.14 33 In the present study both mean arterial blood pressure and heart rate at rest remained within normal range, and hematocrit, PETCO2, and tcPO2 under normocapnic conditions did not change significantly before and after administration of batroxobin (Table 2Up). The oxygen content of blood depends mainly on the volume bound to hemoglobin, together with a relatively small amount of oxygen dissolved in the plasma.34 The oxygen content did not change significantly in this study. Accordingly, we believe it is more likely that the increases in mean MCA blood flow velocity and corrected blood flow velocity (at PETCO2=40 mm Hg) may indicate an increase in CBF as a result of rheological improvement by defibrination without changes in oxygen content or CO2 tension.

Bishop et al35 showed that changes in MCA blood flow velocity correlated reliably with changes in CBF measured with intravenous 133Xe when hypercapnia was induced, and they expressed CO2 reactivity as percent change in mean MCA peak velocity per unit change in PETCO2. Hence, the CO2 reactivity of blood flow in the cerebral arteries can be determined from changes in flow velocity measured by TCD. Ackerman36 reported that CO2 reactivity was proportional to resting blood flow values when mean arterial blood pressure was constant. The law of initial values,37 which states that the higher the initial level, the smaller the response to function-raising agents and the greater the response to function-depressing agents, may affect the observed improvement of CO2 reactivity. In the present study CO2 reactivity increased significantly after administration of batroxobin, which seems due to the significantly increased resting CBF as the result of improvements in hemorheology. From the significant correlation observed between the values of mean MCA blood flow velocity and PETCO2 (r=.644, P<.0001) in our study, changes in MCA blood flow velocity are regarded to be proportional to changes in PETCO2. Therefore, we examined the correlation between CO2 reactivity and blood flow velocity corrected to a standard value of PETCO2=40 mm Hg. As shown in Fig 3Up, the relationship between corrected blood flow velocity and CO2 reactivity was highly significant, which indicated that the increases in CBF velocity were associated with increases in CO2 reactivity. Therefore, we might be able to regard CO2 reactivity as an index of CBF and to consider that CO2 reactivity after administration of batroxobin increased significantly because of the significant increase of CBF after defibrination.

Theoretically, changes in CBF may be affected by one or more of the following mechanisms: (1) altered blood flow velocity through the perfused capillaries; (2) varied number of perfused capillaries (the capillary recruitment hypothesis38 39 ); or (3) modulated diameter of the perfused capillaries. There is a variable distribution of shear stress across the vessel lumen in cerebral microcirculation. Moreover, red cell aggregation and deformability, plasma viscosity, and protein composition have a meaningful influence on blood viscosity in the cerebral microcirculation. Elevated plasma fibrinogen levels result in exaggerated erythrocyte aggregation because plasma fibrinogen plays an important role in overcoming the electronic repulsion between erythrocytes.40 In our study the significant reductions in plasma viscosity and ESR as an index of red cell aggregation due to defibrination might have improved the cerebral circulation because of altered blood flow velocity through the perfused capillaries. Moreover, Sugawara et al41 investigated the effects of batroxobin on the microcirculation by using the rabbit ear chamber method. They observed increases in blood flow and the number of capillaries in the microcirculation after administration of batroxobin. Their results suggest that the mechanism of increases in blood flow velocity after defibrination may be due to increases in the number of perfused capillaries and/or blood flow velocities through the perfused capillaries.

In conclusion, the rheological improvement by defibrination results in increases in MCA blood flow velocity, which are associated with improvements in CO2 reactivity during hypocapnia in healthy subjects. These results may be of importance in various types of brain ischemia and stroke because rheological factors may likewise be of great importance as the determinants of CBF velocity in ischemic brain, where vasodilation is maximal and autoregulation is impaired.


*    Selected Abbreviations and Acronyms
 
CBF = cerebral blood flow
ESR = erythrocyte sedimentation rate
MCA = middle cerebral artery
PETCO2 = end-tidal partial pressure of carbon dioxide
TCD = transcranial Doppler sonography
tcPO2 = transcutaneous partial pressure of oxygen


*    Acknowledgments
 
We would like to express our thanks to Tobishi Pharmaceutical Industries Co Ltd, Japan, for supplying the batroxobin (Defibrase) used in our study.

Received December 4, 1995; revision received April 9, 1996; accepted April 9, 1996.


*    References
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowSubjects and Methods
up arrowResults
up arrowDiscussion
*References
 
1. Yarnell JWG, Baker IA, Sweetnam PM, Bainton D, O'Brien JR, Whitehead PJ, Elwood PC. Fibrinogen, viscosity and white blood cell count are major risk factors for ischemic heart disease: the Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation. 1991;83:836-844.[Abstract/Free Full Text]

2. Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease: the Framingham Study. JAMA. 1987;258:1183-1186.[Abstract/Free Full Text]

3. Meade TW, Mellows S, Brozovic M, Miller GJ. Haemostatic function and ischemic heart disease: principal results of the Northwick Park Heart Study. Lancet. 1986;2:533-537.[Medline] [Order article via Infotrieve]

4. Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984;311:501-505.[Abstract]

5. Thomas DJ, Marshall J, Russel RWR, Wetherley-Mein G, Du Boulay GH, Pearson TC, Symon L, Zilkha E. Effect of hematocrit on cerebral blood flow in man. Lancet. 1977;2:941-943.[Medline] [Order article via Infotrieve]

6. Kusunoki M, Kimura K, Nakamura M, Isaka Y, Yoneda S, Abe H. Effects of hematocrit variations on cerebral blood flow and oxygen transport in ischemic cerebrovascular disease. J Cereb Blood Flow Metab. 1981;1:413-417.[Medline] [Order article via Infotrieve]

7. Grotta J, Ackerman RH, Correia J, Fallick G, Chang J. Whole blood viscosity parameters and cerebral blood flow. Stroke. 1982;13:296-301.[Abstract/Free Full Text]

8. Wood JH, Simeone FA, Fink EA, Golden MA. Correlative aspects of hypervolemic hemodilution with low molecular weight dextran after experimental cerebral artery occlusion. Neurology. 1984;34:24-34.[Abstract/Free Full Text]

9. Tsuda Y, Hartmann A, Weiand J, Solymosi L. Comparison of the effects of infusion with hydroxyethyl starch and low molecular weight dextran on cerebral blood flow and hemorheology in normal baboons. J Neurol Sci. 1987;82:171-180.[Medline] [Order article via Infotrieve]

10. Miller JD, Bell BA. Cerebral blood flow variations with perfusion pressure and metabolism. In: Wood JH, ed. Cerebral Blood Flow. New York, NY: McGraw-Hill Book Co; 1987:119-130.

11. Fukutake K, Fujimaki M, Nagasawa H, Kato M. Clinico-pharmacological observations of batroxobin (Defibrase®) administered to normal human adults. Acta Haematol Jpn. 1981;44:1178-1194.

12. Blattler W, Straub PW, Peyer A. Effect of in vivo produced fibrinogen-fibrin intermediates on viscosity of human blood. Thromb Res. 1974;4:787-801.[Medline] [Order article via Infotrieve]

13. Huch R, Lubbers DW, Huch A. Reliability of transcutaneous monitoring of arterial PO2 in newborn infants. Arch Dis Child. 1974;49:213-218.[Abstract/Free Full Text]

14. Huch A, Huch R, Arner B, Rooth G. Continuous transcutaneous oxygen tension measured with a heated electrode. Scand J Clin Lab Invest. 1973;31:269-275.[Medline] [Order article via Infotrieve]

15. Nicolaides AN, Bowers R, Horbourne T, Kinder PH, Besterman EM. Blood viscosity, red cell flexibility, haematocrit, and plasma-fibrinogen in patients with angina. Lancet. 1977;2:943-945.[Medline] [Order article via Infotrieve]

16. Ito Y, Weinstein M, Aoki I, Harada R, Kimura E. The coil planet centrifuge. Nature. 1966;212:5066;985-987.

17. Aaslid R, Markwalder T-M, Nornes H. Noninvasive transcranial Doppler ultrasound recording of blood velocity in basal cerebral arteries. J Neurosurg. 1982;57:769-774.[Medline] [Order article via Infotrieve]

18. Lindegaard K-F, Bakkle SJ, Grolimund P, Huber P, Aaslid R, Nornes H. Assessment of intracranial hemodynamics in carotid artery disease by noninvasive transcranial Doppler ultrasound. J Neurosurg. 1985;63:890-898.[Medline] [Order article via Infotrieve]

19. Markwalder T-M, Grolimund P, Seiler RW, Roth F, Aaslid R. Dependency of blood flow velocity in the middle cerebral artery on end-tidal carbon dioxide partial pressure: a transcranial ultrasound Doppler study. J Cereb Blood Flow Metab. 1984;4:368-372.[Medline] [Order article via Infotrieve]

20. Ogawa S, Handa N, Matsumoto M, Etani H, Yoneda S, Kimura K, Kamada T. Carbon dioxide reactivity of the blood flow in human basilar artery estimated by the transcranial Doppler method in normal men: a comparison with that of the middle cerebral artery. Ultrasound Med Biol. 1988;14:479-483.[Medline] [Order article via Infotrieve]

21. Huber P, Handa J. Effect of contrast material, hypercapnia, hyperventilation, hypertonic glucose and papaverine on the diameter of the cerebral arteries: angiographic determination in man. Invest Radiol. 1967;2:17-32.[Medline] [Order article via Infotrieve]

22. Jain KK. Some observations on the anatomy of the middle cerebral artery. Can J Surg.. 1964;7:134-139.

23. Sorteberg W, Lindegaard K-F, Rootwelt K, Dahl A, Russell D, Nyberg-Hansen R, Nornes H. Blood velocity and regional blood flow in defined cerebral artery systems. Acta Neurochir (Wien). 1989;97:47-52.[Medline] [Order article via Infotrieve]

24. Maeda H, Etani H, Handa H, Tagaya M, Oku N, Kim B-H, Naka M, Kinosita N, Nukada T, Fukunaga R, Isaka Y, Matsumoto M, Kimura K, Kamada T. A validation study on the reproducibility of transcranial Doppler velocimetry. Ultrasound Med Biol. 1990;16:9-14.[Medline] [Order article via Infotrieve]

25. Sorteberg W, Langmoen IA, Lindegaard K-F, Nornes H. Side-to-side differences and day-to-day variations of transcranial Doppler parameters in normal subjects. J Ultrasound Med. 1990;9:403-409.[Abstract]

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

27. Harper AM. Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the flow through the cerebral cortex. J Neurol Neurosurg Psychiatry.. 1966;29:398-403.[Free Full Text]

28. Saha M, Muppala MR, Castaldo JE, Gee W, Reed JF III, Morris DL. The impact of cardiac index on cerebral hemodynamics. Stroke. 1993;24:1686-1690.[Abstract/Free Full Text]

29. Harper AM, Bell RA. The effect of metabolic acidosis and alkalosis on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiatry.. 1963;26:341-344.[Free Full Text]

30. Brown MM, Wade JPH, Marshall J. Fundamental importance of arterial oxygen content in the regulation of cerebral blood flow in man. Brain. 1985;108:81-93.[Abstract/Free Full Text]

31. Macko RF, Ameriso SF, Akmal M, Paganini-Hill A, Mohler JG, Massry SG, Meiselman HJ, Fisher M. Arterial oxygen content and age are determinants of middle cerebral artery blood flow velocity. Stroke. 1993;24:1025-1028.[Abstract/Free Full Text]

32. Eberhard P, Mindt W, Schafer R. Cutaneous blood gas monitoring in adults. Crit Care Med. 1981;9:702-705.[Medline] [Order article via Infotrieve]

33. Tremper KK, Waxman K, Bowman R, Schoemaker WC. Continuous transcutaneous oxygen monitoring during respiratory failure, cardiac decompensation, cardiac arrest, and CPR. Crit Care Med. 1980;8:377-381.[Medline] [Order article via Infotrieve]

34. Finch CA, Lenfant C. Oxygen transport in man. N Engl J Med. 1972;286:407-415.

35. Bishop CCR, Powell S, Rutt D, Browse NL. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke. 1986;17:913-915.[Abstract/Free Full Text]

36. Ackerman RH. The relationship of regional cerebrovascular CO2 reactivity to blood pressure and regional resting flow. Stroke. 1973;4:725-731.[Abstract/Free Full Text]

37. Wilder J. Modern psychophysiology and the law of initial value. Am J Psychother. 1953;12:199-221.

38. Weiss HR, Buchweitz E, Murtha TJ, Auletta M. Quantitative regional determination of morphometric indices of the total and perfused capillary network in the rat brain. Circ Res. 1982;51:494-503.[Free Full Text]

39. Collins RC, Wagman IL, Lymer L, Matter JM. Distribution and recruitment of capillaries in rat brain. J Cereb Blood Flow Metab. 1987;7(suppl 1):S336. Abstract.

40. Chien S, Jan K-M. Ultrastructural basis of the mechanism of rouleaux formation. Microvasc Res. 1973;5:155-166.[Medline] [Order article via Infotrieve]

41. Sugawara M, Akiyama K, Asano M, Okubo C, Ishii M, Oba M, Umehara N. Effects of batroxobin on microcirculation. J Jpn Soc Biorheol. 1982;159-162.




This article has been cited by other articles:


Home page
Arch NeurolHome page
H. Tomimoto, I. Akiguchi, R. Ohtani, H. Yagi, M. Kanda, H. Shibasaki, and Y. Yamamoto
The Coagulation-Fibrinolysis System in Patients With Leukoaraiosis and Binswanger Disease
Arch Neurol, October 1, 2001; 58(10): 1620 - 1625.
[Abstract] [Full Text] [PDF]


Home page
Arch NeurolHome page
H. Tomimoto, I. Akiguchi, H. Wakita, A. Osaki, M. Hayashi, and Y. Yamamoto
Coagulation Activation in Patients With Binswanger Disease
Arch Neurol, September 1, 1999; 56(9): 1104 - 1108.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
T. K. Pfefferkorn, H.-P. Knuppel, B. R. Jaeger, J. Thiery, and G. F. Hamann
Increased Cerebral CO2 Reactivity After Heparin-Mediated Extracorporal LDL Precipitation (HELP) in Patients With Coronary Heart Disease and Hyperlipidemia
Stroke, September 1, 1999; 30 (9): e1802 - 1806.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
A. Kastrup, C. Thomas, C. Hartmann, and M. Schabet
Sex Dependency of Cerebrovascular CO2 Reactivity in Normal Subjects
Stroke, December 1, 1997; 28(12): 2353 - 2356.
[Abstract] [Full Text]


This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Izumi, Y.
Right arrow Articles by Matsuo, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Izumi, Y.
Right arrow Articles by Matsuo, H.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CARBON DIOXIDE