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Fortschr Neurol Psychiatr 2000; 68(9): 398-412
DOI: 10.1055/s-2000-11798
ORIGINALARBEIT
Georg Thieme Verlag Stuttgart · New York

Mechanismen der zerebralen Autoregulation, Untersuchungsverfahren und Beurteilung mittels transkranieller Doppler-Sonographie

M. J. Hilz, B. Stemper, J. G. Heckmann, B. Neundörfer
  • Neurologische Klinik mit Poliklinik der Universität Erlangen-Nürnberg (Direktor: Prof. Dr. B. Neundörfer)
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Publication History

Publication Date:
31 December 2000 (online)

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Zusammenfassung:

Die zerebrovaskuläre Autoregulation sichert in einem Bereich mittlerer Blutdruckwerte von 50 - 170 mmHg auch bei Blutdruckschwankungen die Konstanz der Hirndurchblutung. Statische und dynamische myogene Mechanismen dämpfen plötzliche Blutdruckschwankungen. Neurogene Einflüsse sympathischer, noradrenerger Fasern regulieren besonders die größeren, proximalen Hirngefäße, aber auch Gefäße mit nur 15 - 20 μm Durchmesser. Parasympathische, gefäßerweiternde Impulse sind von geringerem Einfluss. Monoaminerge Hirnstammkerne wie der dorsale Raphekern, der Locus coeruleus oder der Nucleus reticularis pontis oralis nehmen zusätzlich Einfluss auf die Gefäßmodulation. Metabolische, lokale, parenchymale und endotheliale Substanzen spielen für die Anpassung des Hirngefäßtonus ebenfalls eine entscheidende Rolle. Besonders zu nennen sind Stickoxid, Calcitonin gene related peptide, Substanz P, Endothelin, Kaliumkanäle sowie Entzündungsmediatoren wie Histamin, Bradykinin, Arachidonsäure, Prostaglandine, Leukotriene, freie Radikale oder Serotonin. Die klinische Überprüfung der Autoregulation kann durch kurzfristige Veränderungen des Blutdrucks erfolgen. Hierzu eignen sich Substanzen wie Angiotensin, Phenylephrin oder Natrium-Nitroprussid. Blutdruckänderungen können auch durch eine passive Kipptischbelastung, die „leg-cuff”-Methode nach Aaslid oder das Valsalva-Manöver induziert werden. Die Autoregulation lässt sich auch durch Berechnung der Kohärenz und Phasenbeziehung zwischen Modulationen von Blutdruck und Hirndurchblutung in Ruhe oder während metronomischer Atmung bestimmen. Die Messung der Hirndurchblutung erfolgt mittels transkranieller Doppler-Sonographie der proximalen Arteria cerebri media. Teilweise umstritten ist, ob eine Abnahme der hier gemessenen Strömungsgeschwindigkeit im Sinne einer Vasodilatation am beschallten Gefäßsegment zu werten ist oder eine Blutflussreduktion infolge einer Minderung der Perfusion nachgeschalteter Gefäßabschnitte darstellt. Ausführlich werden zahlreiche klinische und tierexperimentelle Studien erörtert, die deutliche Hinweise auf eine Konstanz des beschallten Gefäßdurchmessers und damit eine Abnahme der nachgeschalteten Perfusion geben. Direkte, intraoperative Messungen des Gefäßdurchmessers bestärken die Schlussfolgerung, dass dopplersonographisch gemessene Änderungen der Strömungsgeschwindigkeit in der proximalen Arteria cerebri media auf Perfusionsänderungen in nachgeschalteten Gefäßbereichen hinweisen. Somit eignet sich die transkranielle Doppler-Sonographie zur Beurteilung der zerebralen Autoregulation.

Mechanisms of Cerebral Autoregulation, Assessment and Interpretation by Means of Transcranial Doppler Sonography:

Cerebrovascular autoregulation assures constancy of cerebral perfusion despite blood pressure changes, as long as mean blood pressure remains in a range between 50 - 170 mmHg. Static and dynamic myogenic mechanisms dampen sudden blood pressure changes. Neurogenic influences of sympathetic, noradrenergic fibers modulate primarily proximal, large diameter segments of cerebral arteries, but also small 15 - 20 μm diameter vessels. Parasympathetic, vasodilating impulses are of less influence. Monoaminergic brainstem centers such as the dorsal raphe nucleus, locus coeruleus or nucleus reticularis pontis oralis also influence vessel tone. Metabolic, local parenchymal and endothelial substances have major impact on cerebral vessel tone. Particularly important are nitric oxide, calcitonin gene related peptide, substance P, endothelin, potassium channels and autocoids such as histamine, bradykinin, arachidonic acid, prostanoids, leucotrienes, free radicals or serotonin. The clinical examination of autoregulation is mostly based on brief blood pressure changes induced by drugs such as angiotensin, phenylephrine or sodium nitroprusside, or by challenge maneuvers. Frequently, blood pressure is challenged by a tilt-table maneuver, the “leg-cuff”-method according to Aaslid, or a Valsalva maneuver. The analysis of coherence and phase relation between spontaneous or metronomic breathing modulation of blood pressure and brain perfusion also assesses autoregulatory function. Cerebral blood flow is determined by means of transcranial Doppler sonography, mostly of the proximal segment of the mid-cerebral artery. There is some controversy whether a decrease of cerebral blood flow velocity measured at this segment indicates vasodilatation at the insonated segment or reflects blood flow reduction due to decreased perfusion of down-stream vessel segments. Various clinical and animal studies are presented demonstrating diameter constancy of the insonated mid-cerebral artery segment and thus indicating that slowing of mid cerebral artery blood flow velocity as assessed by transcranial Doppler sonography is due to a decrease of down-stream perfusion. Direct, intraoperative measurements of vessel diameter confirm this conclusion.

Literatur

  • 1 Bondar R L, Dunphy P T, Moradshahi P, Kassam M S, Blaber A P, Stein F, Freeman R. Cerebrovascular and cardiovascular responses to graded tilt in patients with autonomic failure.  Stroke. 1997;  28 1677-1685
    PubMedGoogle Scholar
  • 2 Aaslid R, Newell D W, Stooss R, Sorteberg W, Lindegaard K F. Assessment of cerebral autoregulation dynamics from simultaneous arterial and venous transcranial Doppler recordings in humans.  Stroke. 1991;  22 1148-1154
    PubMedGoogle Scholar
  • 3 Diehl R R, Berlit P. Funktionelle Dopplersonographie in der Neurologie. Berlin Heidelberg New York: Springer 1996
    Google Scholar
  • 4 Sorteberg W. Cerebral artery blood flow velocity and cerebral blood flow. In: Newell DW, Aaslid R (Hrsg) Transcranial Doppler New York: Raven Press Ltd. 1992: 57-66
    Google Scholar
  • 5 Low P A, Novak V, Spies J M, Novak P, Petty G W. Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS).  Am J Med Sci. 1999;  317 124-133
    PubMedGoogle Scholar
  • 6 Petty G W, Wiebers D O, Meissner I. Transcranial Doppler ultrasonography: clinical applications in cerebrovascular disease.  Majo Clin Proc. 1990;  65 1350-1364
    PubMedGoogle Scholar
  • 7 Aaslid R. The Doppler principle applied to measurement of blood flow velocity in cerebral arteries. In: Aaslid R (Hrsg) Transcranial Doppler sonography Wien: Springer-Verlag 1986: 22-38
    Google Scholar
  • 8 Widder B. Doppler- und Duplexsonographie der hirnversorgenden Arterien. Berlin Heidelberg: Springer-Verlag 1995
    Google Scholar
  • 9 Santalucia P, Feldmann E. The basic transcranial Doppler examination: technique and anatomy. In: Babikian VL, Wechsler LR (Hrsg) Transcranial Doppler ultrasonography Boston: Butterworth-Heinemann 1999: 13-31
    Google Scholar
  • 10 Giller C A, Bowman G, Dyer H, Mootz L, Krippner W. Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy.  Neurosurgery. 1993;  32 737-741 discussion 741-742
    PubMedGoogle Scholar
  • 11 Giller C A, Iacopino D G. Use of middle cerebral velocity and blood pressure for the analysis of cerebral autoregulation at various frequencies: the coherence index.  Neurol Res. 1997;  19 634-640
    PubMedGoogle Scholar
  • 12 Aaslid R, Lindegaard K F, Sorteberg W, Nornes H. Cerebral autoregulation dynamics in humans.  Stroke. 1989;  20 45-52
    CrossrefPubMedGoogle Scholar
  • 13 Novak P, Novak V, Low P A, Petty G W. Transcranial Doppler evaluation in disorders of reduced orthostatic tolerance. In: Low PA (Hrsg). Clinical autonomic disorders Philadelphia: Lippincott-Raven 1997: 349-368
    Google Scholar
  • 14 Diehl R R, Linden D, Lucke D, Berlit P. Phase relationship between cerebral blood flow velocity and blood pressure. A clinical test of autoregulation.  Stroke. 1995;  26 1801-1804
    CrossrefPubMedGoogle Scholar
  • 15 Diehl B, Diehl R R, Stodieck S R, Ringelstein E B. Spontaneous oscillations in cerebral blood flow velocities in middle cerebral arteries in control subjects and patients with epilepsy.  Stroke. 1997;  28 2457-2459
    PubMedGoogle Scholar
  • 16 Symon L. Pathological regulation in cerebral ischemia. In: Wood JH (Hrsg). Cerebral blood flow. Physiologic and clinical aspects New York: McGraw Hill 1987: 423-424
    Google Scholar
  • 17 Paulson O B, Waldemar G. Role of the local renin-angiotensin system in the autoregulation of the cerebral circulation.  Blood Vessels. 1991;  28 231-235
    PubMedGoogle Scholar
  • 18 Wahl M, Schilling L. Regulation of cerebral blood flow - a brief review.  Acta Neurochir Suppl. 1993;  59 3-10
    PubMedGoogle Scholar
  • 19 Ursino M. Mechanisms of cerebral blood flow regulation.  Crit Rev Biomed Eng. 1991;  18 255-288
    PubMedGoogle Scholar
  • 20 McManis P G, Schmelzer J D, Zollman P J, Low P A. Blood flow and autoregulation in somatic and autonomic ganglia. Comparison with sciatic nerve.  Brain. 1997;  120 445-449
    CrossrefPubMedGoogle Scholar
  • 21 Low P A, Tuck R R. Effects of changes of blood pressure, respiratory acidosis and hypoxia on blood flow in the sciatic nerve of the rat.  J Physiol (Lond). 1984;  347 513-524
    CrossrefPubMedGoogle Scholar
  • 22 Takeuchi M, Low P A. Dynamic peripehral nerve metabolic and vascular responses to exsanguination.  Am J Physiol. 1987;  253 E349-353
    PubMedGoogle Scholar
  • 23 Brian Jr J E, Faraci F M, Heistad D D. Recent insights into the regulation of cerebral circulation.  Clin Exp Pharmacol Physiol. 1996;  23 449-457
    PubMedGoogle Scholar
  • 24 Bayliss M M. On the local reaction of the arterial wall to changes in intraluminal pressure.  J Physiol. 1902;  28 220-231
    PubMedGoogle Scholar
  • 25 Johnson P C. The myogenic response. In: Bohr DF, Somlyo AP, Sparks HV (Hrsg). Handbook of Physiology. The Cardiovascular System: Vascular Smooth Muscle Bethesda, MD: American Physiological Society 1980
    Google Scholar
  • 26 Wallis S J, Firth J, Dunn W R. Pressure-induced myogenic responses in human isolated cerebral resistance arteries.  Stroke. 1996;  27 2287-2290; discussion 2291
    PubMedGoogle Scholar
  • 27 Purdy P E, Bevan J A. Adrenergic innervation of large cerebral blood vessels of the rabbit studied by fluorescence microscopy. Absence of features that might contribute to non-uniform change in cerebral blood flow.  Stroke. 1977;  8 82-87
    PubMedGoogle Scholar
  • 28 Owman D, Edvinsson L, Nielsen K C. Autonomic neuroreceptor mechanisms in brain vessels.  Blood Vessels. 1974;  11 2-31
    PubMedGoogle Scholar
  • 29 Edvinsson L. Neurogenic mechanisms in the cerebrovascular bed. Autonomic nerves, amine receptors and their effects on cerebral blood flow.  Acta Physiol Scand Suppl. 1975;  427 1-35
    PubMedGoogle Scholar
  • 30 Morita Y, Hardebo J E, Bouskela E. Influence of cerebrovascular sympathetic, parasympathetic, and sensory nerves on autoregulation and spontaneous vasomotion.  Acta Physiol Scand. 1995;  154 121-130
    PubMedGoogle Scholar
  • 31 Chorobsky J, Penfield W. Cerebral vasodilator nerves and their pathway from the medulla oblongata.  Arch Neurol Psychiatr. 1932;  28 1257
    PubMedGoogle Scholar
  • 32 Cobb S, Finesinger J E. The vagal pathway of the vasodilator impulses.  Arch Neurol Psychiatr. 1932;  28 1243
    PubMedGoogle Scholar
  • 33 Pinard E, Purves M J, Seylaz J, Vasquez J V. The cholinergic pathway to cerebral blood vessels. II. Physiological studies.  Pflugers Arch. 1979;  379 165-172
    PubMedGoogle Scholar
  • 34 Edvinsson L, Hara H, Uddman R. Retrograde tracing of nerve fibers to the rat middle cerebral artery with true blue: colocalization with different peptides.  J Cereb Blood Flow Metab. 1990;  9 212-218
    PubMedGoogle Scholar
  • 35 Hara H, Weir B. Pathway of acetylcholinesterase containing nerves to the major cerebral arteries in rats.  J Comp Neurol. 1986;  250 245-252
    PubMedGoogle Scholar
  • 36 Hara H, Hamill G S, Jacobowitz D M. Origin of cholinergic nerves to the rat major cerebral arteries: coexistence with vasoactive intestinal polypeptide.  Brain Res Bull. 1985;  14 179-188
    CrossrefPubMedGoogle Scholar
  • 37 Moskalenko Y E, Weinstein G. About the neurogenic mechanism of the total cerebral blood flow regulation during changes of systemic blood pressure. In: Mchedlishvili GI, Purves MJ, Kovach AGB (Hrsg). Regulation of cerebral circulation Budapest: Akademiai Kiado 1979: 39
    Google Scholar
  • 38 Moskalenko Y E, Weinstein G B, Demchenko I T, Kislyakov Y Y, Krivchenko A I. Biophysical aspects of cerebral circulation. Oxford: Pergamon Press 1980
    Google Scholar
  • 39 McHedlishvili G I. Arterial behavior and blood circulation in the brain. New York: Plenum Press 1986
    Google Scholar
  • 40 McHedlishvili G. Physiological mechanisms controlling cerebral blood flow.  Stroke. 1980;  11 240-248
    CrossrefPubMedGoogle Scholar
  • 41 Pereira J MMS. Histological, histochemical and microsurgical research on anatomo-physiological basis of neurogenic control of cerebral blood flow. In: Gotoh F, Nagai H, Tazaki Y (Hrsg). Cerebral blood flow and metabolism 1979
    Google Scholar
  • 42 Hoff J T, MacKenzie E T, Harper A M. Responses of the cerebral circulation to hypercapnia and hypoxia after 7th cranial nerve transection in baboons.  Circ Res. 1977;  40 258-262
    PubMedGoogle Scholar
  • 43 Heistad D D, Marcus M L. Total and regional cerebral blood flow during stimulation of carotid baroreceptors.  Stroke. 1976;  7 239-243
    PubMedGoogle Scholar
  • 44 Bonvento G, MacKenzie E T, Edvinsson L. Serotonergic innervation of the cerebral vasculature: relevance to migraine and ischaemia.  Brain Res Rev. 1991;  16 257-263
    CrossrefPubMedGoogle Scholar
  • 45 MacKenzie E T, Scatton B. Cerebral circulatory and metabolic effects of perivascular neurotransmitters.  CRC Crit Rev Clin Neurobiol. 1987;  2 357-419
    PubMedGoogle Scholar
  • 46 Raichle M E, Hartman B K, Eichling J O, Sharpe L G. Central noradrenergic regulation of cerebral blood flow and vascular permeability.  Proc Natl Acad Sci U S A. 1975;  72 3726-3730
    PubMedGoogle Scholar
  • 47 Ohta K, Gotoh F, Shimazu K, Amano T, Komatsumoto S, Hamada J, Takahashi S. Locus coeruleus stimulation exerts different influences on the dynamic changes of cerebral pial and intraparenchymal vessels.  Neurol Res. 1991;  13 164-167
    PubMedGoogle Scholar
  • 48 Kalaria R N, Stockmeier C A, Harik S I. Brain microvessels are innervated by locus coeruleus noradrenergic neurons.  Neuroscience Letters. 1989;  97 203-208
    CrossrefPubMedGoogle Scholar
  • 49 Bonvento G, Lacombe P, Seylaz J. Effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow in the rat.  J Cereb Blood Flow Metab. 1989;  9 251-255
    PubMedGoogle Scholar
  • 50 Saito A, Lee T L. Serotonin as an alternative transmitter in sympathetic nerves of large cerebral arteries of the rabbit.  Circ Res. 1987;  60 220-228
    PubMedGoogle Scholar
  • 51 Chang J Y, Hardebo J E, Owman C. Kinetic studies on uptake of serotonin and noradrenaline into pial arteries of rats.  J Cereb Blood Flow Metab. 1990;  10 22-31
    PubMedGoogle Scholar
  • 52 Maeda M, Takahashi K, Miyazaki M, Ishii S. The role of the central monoamine system and the cholinoceptive pontine area on the oscillation of ICP ‘pressure waves’. In: Miller JD, Teasdale GM, Rowan JO (Hrsg). Intracranial pressure Berlin: Springer Verlag 1986
    Google Scholar
  • 53 Sakas D E, Moskowitz M A, Wei E P, Kontos H A, Kano M, Ogilvy C S. Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures.  Proc Natl Acad Sci U S A. 1989;  86 1401-1405
    PubMedGoogle Scholar
  • 54 Furchgott R F, Zawadzki J V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.  Nature. 1980;  288 373-376
    CrossrefPubMedGoogle Scholar
  • 55 Ignarro L J, Buga G M, Woods K S, Byrns R E, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.  Proc Natl Acad Sci USA. 1987;  84 9265-9269
    PubMedGoogle Scholar
  • 56 Karaki H. Ca2+ localization and sensitivity in vascular smooth muscle.  Trends Pharmacol Sci. 1989;  10 320-325
    CrossrefPubMedGoogle Scholar
  • 57 Toda N, Okamura T. Role of nitric oxide in neurally induced cerebroarterial relaxation.  J Pharmacol Exp Ther. 1991;  258 1027-1034
    PubMedGoogle Scholar
  • 58 Murphy S, Minor R J, Welk G, Harrison D. Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide.  J Neurochem. 1990;  55 349-351
    PubMedGoogle Scholar
  • 59 Lee T, Sarwinski S. Nitric oxidergic neurogenic vasodilation in the porcine basilar artery.  Blood Vessels. 1991;  28 407-412
    PubMedGoogle Scholar
  • 60 Garthwaite J, Garthwaite G, Palmer R, Moncada S. NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices.  Eur J Pharmacol. 1989;  172 413-416
    PubMedGoogle Scholar
  • 61 Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system.  Trends Neurosci. 1991;  14 60-67
    CrossrefPubMedGoogle Scholar
  • 62 Busse R, Mulsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells.  FEBS Lett. 1990;  275 87-90
    CrossrefPubMedGoogle Scholar
  • 63 Bredt D, Hwang P, Snyder S. Localization of nitric oxide synthase indicating a neural role for nitric oxide.  Nature. 1990;  347 768-769
    CrossrefPubMedGoogle Scholar
  • 64 Bredt D, Snyder S. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum.  Proc Natl Acad Sci USA. 1989;  86 9030-9033
    PubMedGoogle Scholar
  • 65 Foerstermann U, Schmidt H HHW, Pollock J S, Heller M, Murad F. Enzymes synthetizing guanylate cyclase-activating factors in endothelial cells, neuroblastoma cells, and rat brain.  J Cardiovasc Pharmacol. 1991;  17 57-64
    PubMedGoogle Scholar
  • 66 Nozaki K, Moskowitz M A, Maynard K I, Koketsu N, Dawson T M, Bredt D S, Snyder S H. Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibers in cerebral arteries.  J Cereb Blood Flow Metab. 1993;  13 70-79
    PubMedGoogle Scholar
  • 67 Yoshida K, Okamura T, Kimura H, Bredt D S, Snyder S H, Toda N. Nitric oxide synthase-immunoreactive nerve fibers in dog cerebral and peripheral arteries.  Brain Res. 1993;  629 67-72
    CrossrefPubMedGoogle Scholar
  • 68 Murphy S, Simmons M L, Agullo L, Garcia A, Feinstein D L, Galea E, Reis D J, Minc-Golomb D, Schwartz J P. Synthesis of nitric oxide in CNS glial cells.  Trends Neurosci. 1993;  16 323-328
    CrossrefPubMedGoogle Scholar
  • 69 Brain Jr J E, Kennedy R H. Modulation of cerebral arterial tone by endothelium-derived relaxing factor.  Am J Physiol. 1993;  264 H1245-1250
    PubMedGoogle Scholar
  • 70 Kovach A G, Szabo C, Benyo Z, Csaki C, Greenberg J H, Reivich M. Effects of NG-nitro-L-arginine and L-arginine on regional cerebral blood flow in the cat.  J Physiol (Lond). 1992;  449 183-196
    PubMedGoogle Scholar
  • 71 Thomsen L L, Iversen H K, Brinck T A, Olesen J. Arterial supersensitivity to nitric oxide (nitroglycerin) in migraine sufferers.  Cephalalgia. 1993;  19 395-399
    PubMedGoogle Scholar
  • 72 Bellantonio P, Micieli G, Buzzi M G, Marcheseli S, Castellano A E, Rossi F, Nappi G. Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study.  Cephalalgia. 1997;  17 183-187
    CrossrefPubMedGoogle Scholar
  • 73 Wahl M, Schilling L, Parsons A A, Kaumann A. Involvement of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in the pial artery dilatation elicited by cortical spreading depression.  Brain Res. 1994;  637 204-210
    CrossrefPubMedGoogle Scholar
  • 74 Lauritzen M, Hansen A J. The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression.  J Cereb Blood Flow Metab. 1992;  12 223-229
    PubMedGoogle Scholar
  • 75 Faraci F M. Role of nitric oxide in regulation of basilar artery tone in vivo.  Am J Physiol. 1990;  259 H1216-1221
    PubMedGoogle Scholar
  • 76 Faraci F M. Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation.  Am J Physiol. 1991;  261 H1038-1042
    PubMedGoogle Scholar
  • 77 Faraci F M, Heistad D D. Endothelium-derived relaxing factor inhibits constrictor responses of large cerebral arteries to serotonin.  J Cereb Blood Flow Metab. 1992;  12 500-506
    PubMedGoogle Scholar
  • 78 Kozniewska E, Oseka M, Stys T. Effects of endothelium-derived nitric oxide on cerebral circulation during normoxia and hypoxia in the rat.  J Cereb Blood Flow Metab. 1992;  12 311-317
    PubMedGoogle Scholar
  • 79 Northington F J, Matherne G P, Berne R M. Competitive inhibition of nitric oxide synthase prevents the cortical hyperemia associated with peripheral nerve stimulation.  Proc Natl Acad Sci USA. 1992;  89 6649-6652
    PubMedGoogle Scholar
  • 80 Tanaka K, Gotoh F, Gomi S, Takashima S, Mihara B, Nogawa S, Nagata E. Inhibition of nitric oxide synthesis induces a significant reduction in local cerebral blood flow in the rat.  Neurosci Lett. 1991;  127 129-132
    CrossrefPubMedGoogle Scholar
  • 81 Wang Q, Paulson O B, Lassen N A. Is autoregulation of cerebral blood flow in rats influenced by nitro-L-arginine, a blocker of the synthesis of nitric oxide.  Acta Physiol Scand. 1992;  145 297-298
    PubMedGoogle Scholar
  • 82 Wahl M, Parsons A A, Schilling L, Kaumann A J. Reduction of pial arterial dilatation during cortical spreading depression by application of an inhibition of nitric oxide synthesis.  Cereb Blood Flow Metabol. 1993;  13 177
    PubMedGoogle Scholar
  • 83 Jaiswal N, Jaiswal R K, Malik K U. Muscarinic receptor-mediated prostacyclin and cGMP synthesis in cultured vascular cells.  Mol Pharmacol. 1991;  40 101-106
    PubMedGoogle Scholar
  • 84 Campbell W B, Halushka P V. Lipid-derived autacoids. Eicosanoids and platelet-activating factors. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG (Hrsg). Goodman & Gilman's The pharmacological basis of therapeutics New York: McGraw-Hill 1996; : 601-616
    Google Scholar
  • 85 Durieu-Trautmann O, Federici C, Creminon C, Foignant-Chaverot N, Roux F, Claire M, Strosberg A D, Couraud P O. Nitric oxide and endothelin secretion by brain microvessel endothelial cells: regulation by cyclic nucleotides.  J Cell Physiol. 1993;  155 104-111
    CrossrefPubMedGoogle Scholar
  • 86 Minc-Golomb D, Tsarfaty I, Schwartz J P. Expression of inducible nitric oxide synthase by neurones following exposure to endotoxin and cytokine.  Br J Pharmacol. 1994;  112 720-722
    PubMedGoogle Scholar
  • 87 Hongo K, Tsukahara T, Kassell N, Ogawa H. Effect of subarachnoid hemorrhage on calcitonin gene-related peptide-induced relaxation in rabbit basilar artery.  Stroke. 1989;  20 100-104
    PubMedGoogle Scholar
  • 88 McCulloch J, Uddman R, Kingman T, Edvinsson L. Calcitonin gene-related peptide: functional role in cerebrovascular regulation.  Proc Natl Acad Sci USA. 1986;  83 5731-5735
    PubMedGoogle Scholar
  • 89 Edvinsson L, Ekman R, Jansen I, McCulloch J, Uddman R. Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects.  J Cereb Blood Flow Metab. 1987;  7 720-728
    PubMedGoogle Scholar
  • 90 Edwards R M, Stack E J, Trizna W. Calcitonin gene-related peptide stimulates adenylate cyclase and relaxes intracerebral arterioles.  J Pharmacol Exp Ther. 1991;  257 1020-1024
    PubMedGoogle Scholar
  • 91 Hong K W, Pyo K M, Lee W S, Yu S S, Rhim B Y. Pharmacological evidence that calcitonin gene-related peptide is implicated in cerebral autoregulation.  Am J Physiol. 1994;  266 H11-16
    PubMedGoogle Scholar
  • 92 Kitazono T, Heistad D D, Faraci F M. Role of ATP-sensitive K+ channels in CGRP-induced dilatation of basilar artery in vivo.  Am J Physiol. 1993;  265 H581-585
    PubMedGoogle Scholar
  • 93 Wei E P, Moskowitz M A, Boccalini P, Kontos H A. Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilatation in feline cerebral arterioles.  Circ Res. 1992;  70 1313-1319
    PubMedGoogle Scholar
  • 94 Moskowitz M A, Wei E P, Saito K, Kontos H A. Trigeminalectomy modifies pial arteriolar responses to hypertension or norepinephrine.  Am J Physiol. 1988;  255 H1-6
    PubMedGoogle Scholar
  • 95 Jansen I, Alafaci C, McCulloch J, Uddman R, Edvinsson L. Tachykinins (substance P, Neurokinin A, neuropeptide K, and neurokin B) in the cerebral circulation: Vasomotor responses in vitro and in situ.  J Cereb Blood Flow Metab. 1991;  11 567-575
    PubMedGoogle Scholar
  • 96 Rosenblum W I, Shimizu T, Nelson G H. Endothelium-dependent effects of substance P and calcitonin gene-related peptide on mouse pial arterioles.  Stroke. 1993;  24 1043-1047 discussion 1047-1048
    PubMedGoogle Scholar
  • 97 Moskowitz M A, Brody M, Liu-Chen L Y. In vitro release of immunoreactive substance P from putative afferent nerve endings in bovine pia arachnoid.  Neuroscience. 1983;  9 809-814
    CrossrefPubMedGoogle Scholar
  • 98 O'Shaughnessy C T, Waldron G J, Connor H E. Lack of effect of sumatriptan and UK-14, 304 on capsaicin-induced relaxation of guinea-pig isolated basilar artery.  Br J Pharmacol. 1993;  108 191-195
    PubMedGoogle Scholar
  • 99 Pfister H W, Kumpfel T, Koedel U. Involvement of substance P in pial arteriolar vasodilatation during pneumococcal meningitis in the rat.  Neuroreport. 1995;  6 1301-1305
    PubMedGoogle Scholar
  • 100 Markowitz S, Saito K, Moskowitz M A. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain.  J Neurosci. 1987;  7 4129-4136
    CrossrefPubMedGoogle Scholar
  • 101 Faraci F M, Kadel K A, Heistad D C. Vascular responses of dura mater.  Am J Physiol. 1989;  257 H157-161
    PubMedGoogle Scholar
  • 102 Edvinsson L, Brodin E, Jansen I, Uddman R. Neurokinin A in cerebral vessels: Characterization, localization and effect in vitro.  Regul Pept. 1988;  20 181-197
    CrossrefPubMedGoogle Scholar
  • 103 Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor.  Nature. 1990;  348 730-732
    CrossrefPubMedGoogle Scholar
  • 104 Sakurai T, Yanigisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor.  Nature. 1990;  348 732-735
    CrossrefPubMedGoogle Scholar
  • 105 Davenport A P, Morton A J. 125 I ET-1, ET-2, and ET-3 and vasoactive intestinal contractor are present in adult rat brain and neurone-enriched primary cultures of embryonic brain cells.  Brain Res. 1991;  554 278-285
    CrossrefPubMedGoogle Scholar
  • 106 Murray M A, Faraci F M, Heistad D D. Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery.  Am J Physiol. 1992;  263 H1643-1649
    PubMedGoogle Scholar
  • 107 Kitazono T, Faraci F M, Heistad D D. Effect of norepinephrine on rat basilar artery in vivo.  Am J Physiol. 1993;  264 H178-182
    PubMedGoogle Scholar
  • 108 Wahl M. Local chemical, neural, and humoral regulation of cerebrovascular resistance vessels.  J Cardiovasc Pharmacol. 1985;  7 S36-46
    PubMedGoogle Scholar
  • 109 Wahl M, Unterberg A, Baethmann A, Schilling L. Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema.  J Cereb Blood Flow Metabol. 1988;  8 621-634
    PubMedGoogle Scholar
  • 110 Schilling L, Wahl M. Histaminergic effects on cerebral hemodynamics. In: Phyllis JW (Hrsg). The regulation of cerebral blood flow Boca Raton: CRC Press 1993: 113-128
    Google Scholar
  • 111 Wahl M, Schilling L. Effects of bradykinin in the cerebral microcirculation. In: Phyllis JW (Hrsg). The regulation of cerebral blood flow Boca Raton: CRC Press 1993: 315-328
    Google Scholar
  • 112 Unterberg A, Schmidt W, Wajl M, Ellis E F, Marmarou A, Baethmann A. Evidence against leukotrienes as mediators of brain edema.  J Neurosurg. 1991;  74 773-780
    PubMedGoogle Scholar
  • 113 Jones S C, Bose B, Furlan A J, Friel H T, Easley K A, Meredith M P, Little J R. CO2 reactivity and heterogeneity of cerebral blood flow in ischemic, border zone, and normal cortex.  Am J Physiol. 1989;  257 H473-H482
    PubMedGoogle Scholar
  • 114 Borgstrom L, Johannsson H, Siesjo B K. The relationship between arterial po2 and cerebral blood flow in hypoxic hypoxia.  Acta Physiol Scand. 1975;  93 423-432
    PubMedGoogle Scholar
  • 115 Kety S S, Schmidt C F. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men.  J Clin Invest. 1948;  27 484-492
    CrossrefPubMedGoogle Scholar
  • 116 Kontos H A, Wei E P, Raper A J, Rosenblum W I, Navari R M, Patterson J LJ. Role of tissue hypoxia in local regulation of cerebral microcirculation.  Am J Physiol. 1978;  234 H582-H591
    PubMedGoogle Scholar
  • 117 Ekstrom-Jodal B, Haggendal E, Linder L E, Nilsson N J. Cerebral blood flow autoregulation at high arterial pressures and different levels of carbon dioxide tension in dogs.  Eur Neurol. 1971;  6 6-10
    PubMedGoogle Scholar
  • 118 Kontos H A. Validity of cerebral arterial blood flow calculations from velocity measurements.  Stroke. 1989;  20 1-3
    PubMedGoogle Scholar
  • 119 Phillis J W. Cerebral vascular responses to hypoxia, hyper- and hypocapnia, and hypotension. In: Phillis JW (Hrsg). The regulation of cerebral blood flow Boca Raton: CRC Press 1993: 249-265
    Google Scholar
  • 120 Novak V, Novak P, Spies J M, Low P A. Autoregulation of cerebral blood flow in orthostatic hypotension.  Stroke. 1998;  29 104-111
    CrossrefPubMedGoogle Scholar
  • 121 Brooks D J, Redmond S, Mathias C J, Bannister R, Symon L. The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of ephedrine.  J Neurol Neurosurg Psychiatry. 1989;  52 962-966
    PubMedGoogle Scholar
  • 122 Gambhir S, Inao S, Tadokoro M, Nishino M, Ito K, Ishigaki T, Kuchiwaki H, Yoshida J. Comparison of vasodilatory effect of carbon dioxide inhalation and intravenous acetazolamide on brain vasculature using positron emission tomography.  Neurol Res. 1997;  19 139-144
    PubMedGoogle Scholar
  • 123 Kuwabara Y, Ichiya Y, Sasaki M, Akashi Y, Yoshida T, Fukumura T, Masuda K. (A comparison of the cerebrovascular responses to CO2 and Diamox in patients with unilateral occlusive cerebral arteries: a H2(15)O PET study).  Kaku Igaku. 1995;  32 569-577
    PubMedGoogle Scholar
  • 124 Ringelstein E B, Van Eyck S, Mertens I. Evaluation of cerebral vasomotor reactivity by various vasodilating stimuli: comparison of CO2 to acetazolamide.  J Cereb Blood Flow Metab. 1992;  12 162-168
    CrossrefPubMedGoogle Scholar
  • 125 Steinling M. The measurement of cerebral perfusion and hemodynamic reserve using SPECT: use in cerebral vascular pathology.  Ann Radiol. 1990;  33 156-169
    PubMedGoogle Scholar
  • 126 Ulrich P T, Becker T, Kempski O S. Correlation of cerebral blood flow and MCA flow velocity measured in healthy volunteers during acetazolamide and CO2-stimulation.  J Neurol Sci. 1995;  129 120-130
    CrossrefPubMedGoogle Scholar
  • 127 Werner C, Kochs E. Cerebral blood flow and cerebral blood flow velocity during angiotensin-induced arterial hypertension in dogs.  Can J Anesth. 1993;  40 755-760
    PubMedGoogle Scholar
  • 128 Larsen F S, Olsen K S, Ejlersen E, Hansen B A, Paulson O B, Knudsen G M. Cerebral blood flow autoregulation and transcranial Doppler sonography in patients with cirrhosis.  Hepatology. 1995;  22 730-736
    CrossrefPubMedGoogle Scholar
  • 129 Smielewski P, Czosnyka M, Kirkpatrick P, McEroy H, Rutkowska H, Pickard J D. Assessment of cerebral autoregulation using carotid artery compression.  Stroke. 1996;  27 2197-2203
    PubMedGoogle Scholar
  • 130 Heckmann J G, Hilz M J, Haagler H, Mück-Weymann M, Neundorfer B. Transcranial Doppler sonography during acute 80 degrees head-down tilt (HDT) for the assessment of cerebral autoregulation in humans.  Neurol Res. 1999;  21 457-462
    PubMedGoogle Scholar
  • 131 Heckmann J G, Mück-Weymann M, Hilz M J, Katalinic A. Autoregulative response of cerebral vessels to elevation in arterial blood pressure, a study using stress TCD.  Clin Auton Res. 1997;  7 47-48
    PubMedGoogle Scholar
  • 132 Heckmann J G, Mück-Weymann M, Katalinic A, Hilz M J, Claus D, Neundorfer B. TCD-Ergometer-Test bei Patienten mit chronischem Kopfschmerz vom Spannungstyp (CKST).  Nervenarzt. 1998;  69 131-136
    CrossrefPubMedGoogle Scholar
  • 133 Heckmann J G, Hilz M J, Katalinic A, Marthol H, Mück-Weymann M, Neundörfer B. Myogenic cerebrovascular autoregulation in migraine measured by stress transcranial Doppler sonography.  Cephalalgia. 1998;  18 133-137
    CrossrefPubMedGoogle Scholar
  • 134 Tiecks F P, Planck J, Haberl R L, Brandt T. Reduction in posterior cerebral artery blood flow velocity during caloric vestibular stimulation.  J Cereb Blood Flow Metab. 1996;  16 1379-1382
    PubMedGoogle Scholar
  • 135 Heckmann J G, Leis S, Mück-Weymann M, Hilz M J, Neundörfer B. Vestibular evoked blood flow response in the basilar artery.  Acta Neurol Scand. 1999;  100 12-17
    PubMedGoogle Scholar
  • 136 Tiecks F P, Douville C, Byrd S, Lam A M, Newell D W. Evaluation of impaired cerebral autoregulation by the Valsalva maneuver.  Stroke. 1996;  27 1177-1182
    PubMedGoogle Scholar
  • 137 Bennaroch E E, Sandroni P, Low P A. The Valsalva maneuver. In: Low PA (Hrsg) Clinical autonomic disorders Minnesota: Little, Brown & Co 1993: 209-215
    Google Scholar
  • 138 Tiecks F P, Lam A M, Matta B F, Strebel S, Douville C, Newell D W. Effects of the Valsalva maneuver on cerebral circulation in healthy adults.  Stroke. 1995;  26 1386-1392
    PubMedGoogle Scholar
  • 139 Hilz M J, Steingrueber M, Hagler A, Axelrod F B. Valsalva Maneuvre demonstrates impaired cerebrovascular autoregulation in familial dysautonomia patients.  Clin Auton Res. 1999;  9 37
    PubMedGoogle Scholar
  • 140 Greenfield Jr J C, Rembert J C, Tindall G T. Transient changes in cerebral vascular resistance during the Valsalva maneuver in man.  Stroke. 1984;  15 76-79
    PubMedGoogle Scholar
  • 141 Nichols J S, Beel J A, Munro L G. Detection of impaired cerebral autoregulation using spectral analysis of intracranial pressure waves.  J Neurotrauma. 1996;  13 439-456
    PubMedGoogle Scholar
  • 142 Birch A A, Dirnhuber M J, Hartley-Davies R, Iannotti F, Neil-Dwyer G. Assessment of autoregulation by means of periodic changes in blood pressure.  Stroke. 1995;  26 834-837
    PubMedGoogle Scholar
  • 143 Diehl R R, Linden D, Luecke D, Berlit P. Spontaneous blood pressure oscillations and cerebral autoregulation.  Clin Auton Res. 1998;  8 7-12
    PubMedGoogle Scholar
  • 144 Müller H, Casty M, Moll R, Zehnder R. Response of middle cerebral artery volume flow to orthostatis.  Cerebrovasc Dis. 1991;  1 82-89
    PubMedGoogle Scholar
  • 145 Thomsen L L, Klingenberg-Iversen H, Boesen F, Olesen J. Transcranial Doppler and cardiovascular responses during cardiovascular autonomic tests in migraineurs during and outside attacks.  Brain. 1995;  118 1319-1327
    PubMedGoogle Scholar
  • 146 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
    PubMedGoogle Scholar
  • 147 Levine B D, Giller C A, Lane L D, Buckey J C, Blomqvist C G. Cerebral versus systemic hemodynamics during graded orthostatic stress in humans.  Circulation. 1994;  90 298-306
    PubMedGoogle Scholar
  • 148 Mueller S M, Heistad D D, Marcus M L. Total and regional cerebral blood flow during hypotension, hypertension, and hypocapnia. Effect of sympathetic denervation in dogs.  Circ Res. 1977;  41 350-356
    CrossrefPubMedGoogle Scholar
  • 149 Lindegaard K F, Lundar T, Wiberg J, Sjoberg D, Aaslid R, Nornes H. Variations in middle cerebral artery blood flow investigated with noninvasive transcranial blood velocity measurements.  Stroke. 1987;  18 1025-1030
    PubMedGoogle Scholar
  • 150 Harper A M, Deshmukh V D, Rowan J O, Jennett W B. The influence of sympathetic nervous activity on cerebral blood flow.  Arch Neurol. 1972;  27 1-6
    PubMedGoogle Scholar
  • 151 DuBoulay G H, Symon L. The anesthesist effect upon the cerebral artery.  Pro R Soc Med. 1971;  64 77-80
    PubMedGoogle Scholar
  • 152 Newell D W, Aaslid R, Lam A, Mayberg T S, Winn H R. Comparison of flow and velocity during dynamic autoregulation testing in humans.  Stroke. 1994;  25 793-797
    PubMedGoogle Scholar
  • 153 Nornes H, Sorteberg W, Nakstad P, Bakke S J, Aaslid R, Lindegaard K F. Haemodynamic aspects of clinical cerebral angiography. Concurrent two vessel monitoring using transcranial Doppler ultrasound.  Acta Neurochir. 1990;  105 89-97
    CrossrefPubMedGoogle Scholar
  • 154 Aaslid R. Visually evoked dynamic blood flow response of the human cerebral circulation.  Stroke. 1987;  18 771-775
    CrossrefPubMedGoogle Scholar
  • 155 Arts M G, Roevros J M. On the instantaneous measurement of bloodflow by ultrasonic means.  Med Biol Eng. 1972;  10 23-34
    PubMedGoogle Scholar
  • 156 Heistad D D, Marcus M L, Abboud F M. Role of large arteries in regulation of cerebral blood flow in dogs.  J Clin Invest. 1978;  62 761-768
    PubMedGoogle Scholar
  • 157 Levy L L, Wallace J D, Stolwijk J A, Poindexter E R. Cerebral blood flow regulation: vascular resistance adjustments in the circle of Willis.  Stroke. 1976;  7 147-150
    PubMedGoogle Scholar
  • 158 Levy L L, Wallace J D. Cerebral blood flow regulation. II. Vasodilator mechanisms.  Stroke. 1977;  8 189-193
    PubMedGoogle Scholar
  • 159 Tuor U I, Farrar J K. Contribution of the inflow arteries to alterations in total cerebrovascular resistance in the rabbit.  Pflugers Arch. 1985;  403 283-288
    PubMedGoogle Scholar
  • 160 Kontos H A, Wei E P, Navari R M, Levasseur J E, Rosenblum W I, Patterson J L. Responses of cerebral arteries and arterioles to acute hypotension and hypertension.  Am J Physiol. 1978;  234 H371-H383
    PubMedGoogle Scholar
  • 161 Baumbach G, Heistad D. Effects of sympathetic stimulation and changes in arterial pressure on segmental resistance of cerebral vessels in rabbits and cats.  Circ Res. 1983;  52 527-533
    PubMedGoogle Scholar
  • 162 Stromberg D, Fox J. Pressures in the pial arterial microcirculation of the cat during changes in systemic arterial blood pressure.  Circ Res. 1972;  31 229-239
    PubMedGoogle Scholar
  • 163 Berne R M, Winn H R, Rubio R. The local regulation of cerebral blood flow.  Prog Cardiovasc Dis. 1981;  24 243-260
    PubMedGoogle Scholar

Prof. Dr. Max J. Hilz

Neurologische Klinik mit Poliklinik der
Universität Erlangen-Nürnberg

Schwabachanlage 6
91054 Erlangen

Email: E-mail: max.hilz@neuro.med.uni-erlangen.de

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