Table Of ContentVASCULAR MECHANISMS OF THE BRAIN
cDYHKUVt5I COCYAVtCTbIX MEXAHVt3MOB rOAOBHOrO M03rA
FUNKTSIYA SOSUDISTYKH MEKHANIZMOV GOLOVNOGO MOZGA
VASCULAR MECHANISMS
OF THE BRAIN
G.I.,Mchedlishvili
Institute of Physiology
Georgian Academy of Sciences
Tbilisi, USSR
Translated from Russian
®
CONSULTANTS BUREAU • NEW YORK-LONDON • 1972
First Printing March 1972
Second Printing July 1973
The Russian text, originally published by Nauka Press in Leningrad in 1968, has been
extensively revised and corrected by the author for this edition. The present
translation is published under an agreement with Mezhdunarodnaya Kniga, the
Soviet book export agency,
<DYHK~Vi51 COCYAViCTbIX MEXAHVi3MOB fOAOBHOfO M03fA
Library of Congress Catalog Card Number 70-141241
ISBN 978-1-4757-0479-2 ISBN 978-1-4757-0477-8 (eBook)
DOI 10.1007/978-1-4757-0477-8
© 1972 Consultants Bureau, New York
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Softcover reprint of the hardcover I st edition 1972
Unit~d Kingdom edition published by Consultants Bureau, London
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PREFACE
The author of this book began his research into the The results of investigations of the cerebral
normal and pathological physiology of the circula circulation conducted in the author's laboratory and
tion in the 1940s. This research followed two main described in this book could never have been ob
lines: to begin with it was devoted to general prob tained without the tremendous efforts of all its staff,
lems of the microcirculation, generalized in the as well as those of speCialists from the Institute of
monograph "The Capillary Circulation" (Georgian PhYSiology, Georgian Academy of Sciences and other
Academy of Sciences, Tbilisi, 1958), while later it scientific institutions in Tbilisi who have collabo
was concerned with the regulation and disturbances rated with me. Among these I should like to men
of the cerebral circulation. Ten years of experi tion especially R. V. Antia, D. G. Baramidze, N. P.
mental research in this field on animals yielded Mitagvaria, L. S. Nikolaishvili and L. G. Ormo
much new information of considerable interest both tsadze (Department of Pathophysiology and Mor
to investigators working in the field of the regional phology of this Institute), G. V. Amashukeli (Georg
circulation and microcirculation, and also to physi ian Postgraduate Medical Institute), V. A. Akhobadze
cians meeting with cerebrovascular distrubances (M. D. Tsinamzgvrishvili Institute of Experimental
in their daily practice. The first general account and Clinical Cardiology, Ministry of Health of the
of these investigations was given in the monograph Georgian SSR), V. M. Gabashvili and M. G. Devda
"Function of the Vascular Mechanisms of the Brain" riani (Institute of Clinical and Experimental Neurol
(Nauka, Leningrad, 1968). Although only a few years ogy, Ministry of Health of the Georgian SSR), P. A.
have elapsed since the publication of that book, much Kometiani and V. N. Chikvaidze (Department of Bio
experimental material has been collected in the in chemistry of the Institute of Physiology, Georgian
tervening period, with the result that the contents Academy of Sciences) and A. I. Roitbak (Laboratory
and arrangement of some of the chapters must be of General PhYSiology of the Cerebral Cortex of
modified for the second edition, and new results of that Institute). An important part in the investiga
research and new bibliographic references added. tions was played by joint work with scientists abroad
The first stage of this research into the cere and in other cities of the USSR: E. K. Plechkova,
bral circulation was undertaken in the laboratory N. B. Lavrent'eva, O. Ya. Kaufman and A. V. Boro
directed by the eminent Soviet pathophysiologist and dula (Institute of Normal and Pathological Physiol
honorary member of the Georgian Academy of Sci ogy, Academy of Medical Sciences of the USSR,
ences Professor V. V. Voronin, who until 1960 was Moscow), V. M. Samvelian (Institute of Cardiology
head of the Department of Pathological PhYSiology and Heart Surgery, Ministry of Health of the Arme
and Morphology at the Institute of Physiology of the nian SSR, Erevan), T. Garbulinski and A. Gosk
Georgian Academy of Sciences. This Institute was (Wroclaw, Poland), and also with D. Ingvar, C.
founded and the whole of its activity has been con Owman, B. Falck and R. Ekberg (Lund, Sweden).
stantly directed by Professor I. S. Beritashvili, I take this opportunity of expreSSing my sincere
Academician of the Academy of Sciences of the thanks to all of them.
USSR, the Academy of Medical Sciences of the USSR, The author is deeply grateful to all his col
and the Georgian Academy of Sciences. The scien leagues and friends who, by their friendly advice
tific stmosphere of this Institute and the daily con and critical comments, have asi!§isted him with
tacts with the workers in its laboratories went a these investigations of the cerebral circulation and
long way toward ensuring the success of the re with the preparation of this book for publication.
search. The author hopes that this book will promote
v
vi PREFACE
further experimental research into the physiology If this hope is even partly fulfilled, he will be able
and pathology of the cerebral circulation and that to rest assured that the long and sustained work of
it will also prove useful to the practicing physician. himself and his colleagues will not have been in vain.
Professor George Mchedlishvili, M.D.,
Department of Pathophysiology
Institute of Physiology
Georgian Academy of SCiences,
Tbilisi, USSR
CONTENTS
Introduction ................................................ . . . . . . . . . 1
PART 1
FUNCTIONAL BEHAVIOR OF THE VASCULAR MECHANISMS
OF THE BRAIN UNDER VARIOUS CONDITIONS
Chapter I
Investigating the Behavior of Different Parts of the Cerebrovascular System 7
Chapter II
Vascular Mechanisms and Changes in Systemic Arterial Pressure ............ . 17
Role of the Major Arteries in Maintaining a Constant Inflow of Blood into the
Circle of Willis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . 19
Functional Behavior of the Pial, Precortical, and Cortical Arteries during Changes
of the Systemic Arterial Pressure ........... . ............. . 20
Functional Insufficiency of Vascular Mechanisms during Changes in Systemic
Arterial Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . 23
Chapter ill
Intracranial Circulatory Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25
Occlusion of Jugular Veins (Mild and Transient Stagnation of Venous Blood) ..... . 25
Severe Stagnation of Blood in the Cerebral Vessels Resulting from Occlusion of the
Cranial (Superior) Vena Cava ...... . 27
Traumatic Cerebral Edema . . . . . . . . . . . 29
Systemic Asphyxia ................ . 32
Postischemic States . . . . . . . . . . . . . . . . 35
Increased Activity of the Cerebral Cortex . 39
Ischemia of the Cerebral Cortex Resulting from Occlusion of the Pial Arteries 43
Collateral Blood Supply. . . . . . . . . . . . . . . . . . . . . . . . . 45
Terminal State Preceding Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Chapter IV
Causes of Primary Disturbance of the Cerebral Circulation .....••.............•. 55
Spasm of the Cerebral Arteries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . 55
Significant Increase of Resistance in the Very Small Cerebral Vessels as a Cause of
Cerebrovascular Disturbances ................................. . 61
Double Significance of Some Compensatory Responses in Cerebrovascular Disorders. 64
Chapter V
Organization of the Vascular Mechanisms .................................. . 67
vii
viii CONTENTS
PART 2
PHYSIOLOGICAL MECHANISMS OF FUNCTIONAL
BEHAVIOR OF THE CEREBRAL ARTERIES
Chapter VI
The Major Arteries ............................................... . 75
Direct Effects of Physiologically Active Substances on the Internal Carotid Arteries 75
Sympathetic and Other Nervous Effects on the Major Arteries . . . . . ......... . 77
Role of Reflexes from the Carotid Sinus Receptors in Autoregulatory Responses of
Major Arteries ........................... . 81
Reflex Vasoconstriction Arising from Intracranial Receptors ............... . 83
Chapter VII
The Pial Arteries. 87
Humoral Feedback from Brain Tissue to the Pial Arteries ....... . 87
Nervous Feedback Mechanism from Brain Tissue to the Pial Arteries 90
Concluding Remarks .. 99
Bibliography . . . . . . . 103
INTRODUCTION
The brain certainly needs a more constant and bet tective in character. It is only by thorough analysis
ter regulated blood supply than any other of the of the physiological principles governing these phe
body. The blood flow through a human brain weigh nomena that the physician, when he attempts to in
ing 1400 g (approximately 2% of the body weight) is terfere with the processes taking place in the body,
about 750 ml/min, Le., approximately 15-20% of can be confident that he is doing good, and not harm,
all blood expelled by the heart into the systemic to the patient.
circulation passes through the brain per minute The history of investigations of the physiology
[143]. In 1 min the brain utilizes on the average of the cerebral circulation has passed through sev
49 ml of oxygen, Le., about 20% of the total quantity eral periods. a) The first, which lasted until the
utilized by all tissues of the body [365], and 76 ml end of the 19th century, was dominated by the
glucose, Le., 70% of all the glucose issuing from Monro-Kellie doctrine [278,140]. Proceeding :om
f
the liver [340]. Under normal conditions the prin the assumption that the skull is rigid and its C In
cipal source of energy needed for neuron function tents incompressible, it was thought that the blood
is oxidation of glucose. However, the brain has no volume and circulation in the brain must remain
reserve of carbohydrates, and still less of oxygen, fixed whatever the conditions. b) After the appear
so that its normal metabolism depends entirely on ance of Leonard Hill's classical monograph [111] a
a constant supply of blood-borne energy-giving ma new concept came to be accepted: the cerebral cir
terials. If the circulation stops, severe metabolic culation may vary but only by the operation of an
disturbances at once arise in the brain. The high extrinsic mechanism, Le., through changes in the
sensitivity of the brain to disturbances of its blood systemic arterial pressure, and not by vasomotor
supply, on the one hand, and the comparative vulner responses of the cerebral blood vessels; the prin
ability of its vascular system, on the other hand, cipal postulate of the Monro-Kellie doctrine, that
explain why changes in brain function are most fre the blood volume within the skull remains constant,
quently dependent on circulatory disorders. Such was thus still accepted. This concept was held al
changes include headaches, disturbances of ability most universally until the 1930s. c) With the grad
to do intellectual work, loss of memory in elderly ual accumulation of experimental data, evidence
people; and a great variety of neurological disorders was obtained for the important role of an intrinsic
caused by brain trauma, apoplexy, etc. could be mechanism, Le., of the vasomotor responses of the
mentioned. During circulatory deficiency not all cerebral arteries, in the control of blood supply to
brain functions are equally sensitive, of course, to the brain. This concept was summarized in a num
oxygen lack: speech and intellectual activity are the ber of publications which appeared in the 1950s
first to be disturbed, loss of consciousness takes [341,148,170,367,175].
place 5 -6 sec after complete interruption of the Since in most of the investigations to that
Circulation, and death ensues after 4-5 min [340]. period all that had been done was to record the
Progress in practical mediCine, so far as the blood flow or the resistance in the vascular sys
development and effects of cerebrovascular distur tem of the brain, the results could not possibly
bances are concerned, is primarily dependent on show how the different vessels of the brain partici
experimental investigations of the cerebral circu pate in regulation and in disturbances of the re
lation under normal and pathological conditions. gional circulation. It was therefore necessary to
Without them it would be impossible to understand assume that either regulation of the local hemo
which vascular responses and Circulatory phenom dynamics in the brain is effected by the "cerebral
ena are harmful or unsuited to brain activity and vessels" (without specifying which vessels), or,
which, on the contrary, are compensatory or pro- alternatively, the leading role was ascribed to the
1
2 INTRODUCTION
"arterioles." Although originally the term "arte The concept of a distinctive role of different
rioles" had the concrete meaning of the smallest parts of the arterial system of organs was concisely
precapillary arteries, the walls of which contain formulated by Voronin [397], who concluded from
a single layer of muscle cells, later on it was ap experimental results obtained in his laboratory
plied to all small arteries (down to 300-500J..! in [28,396,409] that the larger arteries of organs
caliber) capable of changing their lumen within (those possessing a well-developed muscular layer)
wide limits. are directly concerned with regulation of the sys
By the end of the 1950s a new problem had temic arterial pressure, while the smaller arteries
arisen. It was necessary to elucidate the general regulate the blood supply of the tissue in accordance
principles governing the functional behavior of the with its metabolic needs. These researches were
intrinsic mechanisms regulating the cerebral cir continued by Voronin's co-workers: the present
culation and concerned in its disorders. This prob author studied the cerebral Circulation, other
lem was closely related to those engaging the at workers [91] studied the functional peculiarities
tention of researchers in the microcirculation field. of the skin arteries, and so on.
To study differences in the functional behavior of Until recently very few experimental data con
different parts of the vascular system of the brain cerning the functional behavior of different parts of
and, in particular, differences in their responses the vascular system of the brain had been published.
to nervous and humoral influences, their role in The most likely explanations of this fact are, first,
regulating the blood supply to the brain, in com that the problem was simply not considered by the
pensating cerebrovascular disorders, and in the overwhelming majority of investigators and, sec
genesis of circulatory disturbances in the central ond, the usual approaches and methods could not
nervous system, it was essential that the research elucidate the peculiarities of the functional behavior
methods used should yield, not indirect data, but of different parts of the cerebrovascular system.
concrete and quantitative information concerning The characteristic physiological behavior of blood
the functional behavior of each part of the vascular vessels regulating the cerebral circulation could be
system of the brain, and especially of its arterial found out under the conditions either when they cor
system. It is well known that in the vascular sys relate the blood supply with changes in brain func
tem of every organ, the principal "controllable" tion under physiological conditions or when com
component is the capillary Circulation, and the pensation of cerebrovascular disturbances takes
most active "controlling" part the arterial vessels. place under pathological conditions. The study of
The intenSity of the capillary circulation and all its the functional behavior of the vascular mechanisms
changes under normal and pathological conditions under pathological conditions appeared to the author
are dependent on the total resistance of the whole to be most promising, for these conditions are ex
extent of the arterial system of the organ, starting tremely varied and, consequently, many different
from the main arteries as they enter the organ types of functional behavior of different parts of the
(branches of the central arteries, the pressure in cerebrovascular system are available for study;
which is regarded as the systemic arterial pres moreover, under pathological conditions the changes
sure), and ending with the tiny precapillary arteri may be much more marked quantitatively and, there
oles. At a given moment, depending on the concrete fore, more easily detectable than under physiologi
conditions, one or another part of the arterial sys cal conditions.
tem of any organ may change its lumen like a valve, At the very outset of the author's investiga
and thus bring about appropriate changes in the tions of the cerebral circulation (in 1956-1957) the
capillary circulation. The author's investigations active role of the major arteries of the brain in
into the mechanisms of the microcirculation [208] regulating the cerebral blood supply was discovered
have demonstrated that the intrinsic arteries of an quite unexpectedly: in a study of cortical capillaries
organ play an important role in modifying many as during venous stagnation it was found that intravital
pects of the capillary circulation: the velocity of the fixation of the cortex with excision of part of the
blood flow in the capillaries, the distribution of hemispheres (for microscopic investigation) imme
blood cells in capillary networks, changes in the diately after occlusion of the jugular veins was ac
number of active capillaries, the onset and com companied by unexpectedly slight bleeding. The
pensation of disturbances of the capillary circula gradual accumulation of experimental data eventu
tion, such as intracapillary aggregation of erythro ally showed that under these conditions venous stag
cytes, the complex group of circulatory changes in nation is not present in the brain. It was later dis
an inflanunatory focus, and so on. covered that this is because of constriction of the
INTRODUCTION 3
whole system of major arteries of the brain, and cular mechanism" into circulatory physiology was
that it is a compensatory reaction, Le., a manifes determined by three factors: a) the need to draw a
tation of regulation of the cerebral circulation. The sharp line between parts of the vascular system of
regulatory role of the major arteries of the brain an organ with different functions and to study their
was subsequently demonstrated under different con role in its contribution to its peripheral resistance;
ditions. It was soon found that responses (constric b) the need for combined investigation of all the
tion or dilatation) of individual vessels throughout functional properties of these vascular regions; and
the arterial system cannot only differ in degree, c) the need to establish the functional organization
but also be opposite in direction. This compelled of the intrinsic mechanisms of regulation and dis
the introduction of a new concept of "vascular turbance of the local circulation and microcircula
mechanism," implying a combination of functional tion in each organ. Under present-day conditions,
properties of a given vessel or vessels, or in other it would be impossible without such an approach to
words, those features of the structure and function understand the mechanisms regulating the circula
of the vessel walls which determine their responses tion and microcirculation within an organ or to be
to various stimuli, together with the stimuli (ner able to treat their disorders in disease. From this
vous, humoral, or other) which control the size of point of view, the vascular system of the brain is
the lumen and, consequently, the resistance in these in a slightly advantageous position, for in the case
vessels. From the author's point of view, those of most other organs neither suitable methods of
parts of a blood vessel which, throughout their ex investigation nor experimental results reflecting
tent, exhibit relatively uniform functional proper the functional behavior of the various vascular
ties and give identical responses to various stimuli, mechanisms are yet available.
can be regarded as a separate vascular mechanism. Since this book is devoted only to one partic
From work done during the 1960s, it has become ular aspect of investigation of the cerebral circula
apparent that functional behavior may differ in the tion, which has been widely developed in the labo
following parts of the cerebrovascular system: ratory directed by its author, the reader will find
a) the major arteries of the brain* (the internal that it contains principally experimental data ema
carotid and vertebral arteries), b) the pial arte nating from that laboratory, and that it does not at
ries (the intermediate segments between the pial tempt to give an exhaustive account of the history
and cortical arterieS), d) the intracerebral arteries of research in the field of the physiology and path
and arterioles, e) the capillaries, f) the pial veins, ology of the cerebral circulation in general.
and g) the emissary veins of the skull carrying
blood from the brain sinuses. Very probably with • In a number of papers written by the author these arteries were
improvements in research methods it will later be called "regional arteries of the brain," because in Voronin's
possible to differentiate the vascular mechanisms laboratories the term "regional arteries" was used to describe
all arteries of medium caliber and of muscular type entering
of the brain, from the standpoint of functional be
an organ and playing an important role in the creation of pe
havior, in even greater detail. This may apply to
ripheral resistance. Later, however, the use of this term led to
blood vessels of different caliber and also to ves
difficulties because the word "regional" literally means "local"
sels in different parts of the brain. when applied to arteries, and many writers use this term to de
The introduction of this new concept of "vas- scribe all the arteries of an organ, of whatever type.
