Biophysical Aspects of Cerebral Circulation

Britain

Introduction

THE study of the physiological mechanisms which ensure an adequate blood supply to the brain occupies a special place in cardiovascular physiology. This is due to its importance for the normal functioning of the organism. It is known in clinical practice that even brief, minor disturbances in the cerebral circulation can cause damage to certain brain functions. Statistics show that cerebrovascular disorders are the third commonest cause of death, exceeded only by cancer and coronary lesions (WHO publication, No. 469, Geneva, 1973). The main reason for the extreme sensitivity of the brain to circulatory impairment is its intense metabolism and the absence of a substrate which could maintain the neurons anaerobically. Therefore, the circulation of the brain must ensure a good blood supply under the varied conditions to which the organism is subjected.

The second important distinctive feature of the cerebral circulatory system is its structural and functional organization which is related to its position within the cranial cavity. The cranium also contains cerebrospinal fluid (CSF) which is in direct hydraulic contact with the cerebral vessels. Increases or decreases of the cerebral blood volume can result in changes of the volume of CSF which can flow into or out of the spinal canal. The concept of the intracranial circulation must take into account the CSF as well as the intracranial blood vessels and their relationship within the closed cranium from which the CSF can pass into the spinal canal or vice versa.

The literature dealing with this part of the cardiovascular system has become voluminous, especially recently. Thus, the quarterly Cerebrovascular Bibliography published by the National Institute of Health, Bethesda, USA, contains over 1000 titles. This indicates the difficulty of writing a comprehensive review of the literature in this field. The number of review articles has increased during recent years, and a laudable trend has been the publication of symposia on various aspects of the cerebral circulation. Among these are the international symposia organized by Ingvar and Lassen and the Tbilisi symposia organized by Mchedlishvili. The Third International Symposium on Intracranial Pressure took place in 1976.

The programs of these symposia show clearly that the physiology of the intracranial circulation can be divided into several major areas. The choice of theme for each symposium is usually determined by the particular interests of the organizers as it is difficult to cover all aspects of the field. The titles of symposia have, however, remained general and do not single out particular aspects of the physiology of the intracranial circulation. Thus, the symposia held in Copenhagen in 1974 and in Glasgow in 1975 were largely devoted to investigations of the intensity of total or localized cerebral blood flow in normal or diseased human subjects using the Kety–Schmidt method. The Tbilisi symposia have concentrated on the role of neurogenic mechanisms in the regulation of the cerebral circulation. Regular symposia on intracranial pressure are a sign that yet another aspect of the physiology of the intracranial circulation has gained importance.

Recent developments in the field of cardiovascular physiology indicate the growing importance of analyses of the biophysical aspects of the intracranial circulation. The special approach used in such investigations is that of treating the cerebral circulation as a complex system whose function it is to maintain the essential supply of metabolites to the neurons and to remove waste substances from them. This can be achieved only with the help of a regulatory component which can only be understood in terms of the physical and chemical interactions within the system.

The interrelationships between the respective volumes and pressures of arterial and venous blood and CSF within the closed cranial cavity as well as the laws governing blood flow must be given due consideration. These physical factors are the main determinants of the state of the intracranial circulation. To sum up, a biophysical approach to the intracranial circulation involves the analysis of interrelationships of the factors which contribute to its function, finding correlations between their quantitative changes and analyzing the physical properties of its structural components by a systems approach. Until recently the biophysical approach to the study of the intracranial circulation was largely confined to the use of complicated recording devices. Such methods have been inappropriately described as biophysical. Consequently, only a few of the biophysical aspects of the cerebral circulation have been studied so far. These can be roughly divided into two categories. The first treats the cerebral circulation as a whole, the second deals with correlations between blood supply, neurological activity, and metabolism at a tissue level, i.e., it treats the brain as a complex, functionally heterogeneous structure whose activity is in constant flux.

The purpose of this monograph is to bring together data from published work on the cerebral circulation and data recently obtained in the Laboratory for the Study of the Regulation of the Cerebral Circulation of the Sechenov Institute for Evolutionary Physiology and Biochemistry of the Academy of Science of the USSR. Some of the studies of the biophysical aspects of the intracranial circulation have been carried out by means of mathematical models which can be useful in the study of complex systems. The monograph consists of three parts. The first (Chapter 1), devoted to methodology, attempts to explain the special features of a biophysical approach. The biophysical principles of the most commonly used modern methods are described in detail (clearance method, rheoencephalography, etc.) as well as original or modified methods devised in our laboratory. Methods used by us to analyze and process information are also described. Special attention is given to criteria used for selecting particular stimuli or functional tests.

Another important approach is the representation of the system in the form of a mathematical model. This subject is dealt with only briefly as one of the co-authors has written a book entirely devoted to this subject (Kislyakov, 1975).

The second part of this book (Chapters 2 and 3) examines all the biophysical aspects of the cerebral circulatory system as a functional unit and deals with some principles of its regulation. The results of systems analysis using mathematical modeling are presented in broad outline. A special section deals with the mechanical stability of the cerebral circulation which is approached through analysis of the biophysical relationships within the system. These problems are of special significance as man is exposed to ever-growing mechanical stresses.

The last part of the book (Chapter 4) deals with processes related to the regional cerebral circulation. Such investigations focus mainly on the relationship between periodically fluctuating factors affecting limited areas of brain tissue. In these investigations, systems analysis is used to test the hypothesis of the interdependence of neurogenic and metabolic processes in regulating the regional cerebral circulation.

Many of the problems dealt with in this monograph can rightfully be regarded as physiological since there is no hard and fast separation between the biophysics and physiology of the cardiovascular system as a whole. Many biophysical processes in the circulatory system are directly related to its function and regulation. Strictly speaking, we have examined a group of processes related to the physiology of the intracranial circulation. Therefore, it is simplest to describe our task as the explanation of those biophysical aspects of the intracranial circulation which are essential for an understanding of its normal and abnormal function.

CHAPTER 1

Methods of Investigation of the Intracranial Circulation

Publisher Summary

This chapter discusses the methods of investigation of the regional or total cerebral blood flow from the point of view of systems analysis. The systems analysis approach means treating the object of investigation as a complex system. This approach involves the examination of the system as a whole while simultaneously giving due consideration to the interaction of all its functionally significant components. The systems analysis involves special principles and methods, one of which is mathematical modelling that has wide applications. It can be the most appropriate method where the activities of a particular functional unit are well-enough understood to predict their direction and to assess its functional state at any given time. The systems approach is based on a clear delineation of the functional system under investigation and the identification of the channels by which it communicates with other systems. The channels through which it receives external influences are its input; the results of its activities are its output.

INVESTIGATIONS of the blood supply to the brain and its underlying biophysical processes must adhere to the same principles which apply to investigations of functional systems in general, i.e., the information obtained must throw light on the functional processes as well as the quality of the functioning of the system. The above proposition follows from a systems analysis approach, i.e., from treating the object of investigation as a complex system. By contrast with traditional physiological methods of examining separate factors within a functional unit, the systems analysis approach involves the examination of the system as a whole while simultaneously giving due consideration to the interaction of all its functionally significant components. Systems analysis involves special principles and methods, one of which is mathematical modeling which has very wide applications. Systems analysis can be the most appropriate method where the activities of a particular functional unit are well enough understood to predict their direction and to assess its functional state at any given time. The systems approach is based on a clear delineation of the functional system under investigation and the identification of the channels by which it communicates with other systems. The channels through which it receives external influences are its input, the results of its activities are its output. (Fig. 1)

FIG. 1 General principles of physiological investigations from a systems point of view.

In studies of functional systems by the method of systems analysis, three groups of variables must be recorded simultaneously. These are: (1) variables which characterize the changes caused in the system by way of channels connecting it with other systems or its input; (2) variables which characterize the results of its activities or its output; (3) variables which characterize the means by which the system solves its functional tasks or the changes in its state.

It is evident that an understanding of the first two groups of variables makes it possible to assess the quality of the functioning of the system in question. The third group makes it possible to understand the mechanisms by which the functional task is accomplished.

This general approach to investigations of complex systems is useful in studying complex physiological systems, such as the intracranial circulation, and should be accepted as one of the valid biophysical approaches to this problem. Consequently, use is made by us of conclusions drawn from a systems approach when appraising the methods of investigation of the cerebral circulation in this chapter.

In regard to the intracranial circulation as a functional unit, both flow of blood into the cranium and out of it must be regarded as input, since the cerebral blood flow is determined by both arterial pressure and venous drainage. In examining the functioning of separate regions of the brain whose activity fluctuates constantly, the input is the functional activity of the region under investigation. The output both at the level of the whole brain and of its separate regions is the level of blood flow.

Under normal physiological conditions and in the absence of external stimuli, the input and output of a system are obviously in a state of balance. In order to assess the quality of its functioning, the state of the system under investigation must be changed by altering the input and observing the output. This can be achieved by a variety of functional interventions. The success of the investigation largely depends on selection of appropriate intervention. The use of functional tests is also essential for the study of the mechanisms underlying the functioning of the system under investigation, but in that case they serve the purpose of elucidating the role of individual factors which contribute to the total functioning of the system. It is important for functional tests to be quantifiable and to have a well-defined effect on the input or the state of the system.

One way of representing the organization of investigation of the intracranial circulatory system is by means of a scheme as illustrated in Fig. 2. Such a scheme envisages automated processing of results and the plan of the experiments as well as the variables and experimental intervention mentioned above. It is evident that the measurements which must be recorded to study the functioning of the regional cerebral circulation are different from those required in studies of the total cerebral circulation. In the case of the former, the input is the functional state of a particular part of the brain, in the latter it is the flow of blood into and out of the brain, i.e., the level of the systemic arterial and venous pressures. The variables which describe the state of the regional or total cerebral circulation are more alike. For example, in both cases changes in blood volume are a good indication of the tone of blood vessels and their hydraulic resistance (Moskalenko, et al., 1976a). Additional information on the state of the total cerebral circulation can be gained by measuring the intracranial pressures (ICP). The state of regional blood flow is reflected in the tensions of oxygen (PO2) and carbon dioxide (PCO2) in brain tissue. The output of the regional as well as of the total blood supply to the brain can be determined by recording the intensity of blood flow in part or the whole of the brain.

FIG. 2 Scheme of investigation of the cerebral circulatory system. LCBF, local cerebral blood flow; Ap, arterial pressure; Vp venous pressure; EPG, electroplethysmography; ICP, intracranial pressure; TCBF, temperature recording of the blood flow.

Experimental interventions which help to demonstrate the special features of the functioning of the cerebral circulation are indispensable. Such procedures can affect the flow of blood into and out of the brain, intracranial pressure, acid-base balance of the CSF, etc., i.e., they affect the input into the system and its state depending on the objectives of the investigation. Naturally occurring processes, such as periodic fluctuations of the arterial and venous pressure, related to cardiac and respiratory activity, also belong to the factors which can be studied profitably. As shown in Fig. 2, it is possible to vary the functional interventions according to the state of the system under investigation. This can also be achieved by using a computer in the experimental design. It is also very useful in analyzing experimental results.

The effectiveness of investigations of the cerebral circulation is determined not only by the sophistication of methods, but also by the selection of optimal experimental procedures, such as selection of appropriate stimuli. Experiments based on such principles make it possible to elucidate the biophysical characteristics of the regulatory system of both the regional and general cerebral circulation from the changes observed in the input and output of the system in response to certain experimental interventions. The selection of appropriate parameters makes it possible to understand the mechanisms underlying the observed phenomena.

Methods of Recording Variables of the Total Cerebral Circulation

The brain requires a copious blood supply and maintains a fairly constant high level of blood flow under most diverse physiological conditions that affect the perfusion pressure. According to our view of the system of the total cerebral circulation, its most basic parameter is the intensity of blood flow. This, in turn, depends on the arterial and venous blood pressures, the tension of blood gases, and on the state of the system itself which is determined by the blood volume within the cranial cavity, the ICP, the tone of cranial blood vessels, the consumption of oxygen and glucose by the brain, its functional activity, etc. The functioning of the system can only be assessed by simultaneously recording all these variables since, for example, the volume of the total cerebral circulation does not by itself reflect prevailing hemodynamic conditions. Similarly, the arterial and venous pressures, i.e., the input into the system, give little indication of the cerebral blood volume or the rate of blood flow.

Methods of recording variables which characterize the total cerebral circulatory system are presented in this chapter. The most widely used of these methods, sometimes modified, are also used to study the regional cerebral circulation. For this reason, only the general principles of these methods are discussed. Details of methods used to study the regional blood flow are deferred to the next section.

Recording of Intracranial and Intravascular Pressures

Pressure measurements provide information of two kinds. Measurement of the pressure in cavities filled with CSF yield information on the state of the system in question, whereas measurements of the internal pressure of blood vessels supplying the brain characterize the input into that system. The transducers used may be the same for both, but the techniques of measurement are different.

Since the end of the last century, the cerebrospinal pressure has been measured both experimentally and clinically by connecting a manometer tube to a needle introduced into the subarachnoid space. The level of fluid in the tube has been used to determine the pressure. The pressure recorded in this way is less than the true pressure by ΔP, which is calculated by the following formula:

(1)

in which S is the area of the cross-section of the manometer, n is the height of the liquid within the tube, α is the coefficient of elasticity of the craniospinal cavity, V0 is the volume of fluid within that cavity.

A number of measures has been proposed to overcome these defects. Belenovsky (1959) and Teregulov (1959) have suggested that the tube first be filled with saline solution. Ugryumov et al. (1957) have proposed the use of a compensating air chamber. A substantial advance came with the introduction of various types of membrane manometers using electrical recording of displacements of the membrane. This has made it possible to devise manometers which are sensitive, require a small working volume, and possess the required frequency characteristics which make them useful for recording rapid pulsatile fluctuations.

Electromanometers are classified according to the principle by which pressure is translated into piezo-electric, mechano-electric, photoelectric, tensometric, or inductive energy. The piezo-electric principle has been used to record ICP by Naumenko (1957), Belekhova (1958), and others. Piezo-manometers are very sensitive, but do not record actual pressure. They record the rate of pressure changes. Therefore, they cannot be used to record either the true form of fluid pulsations or slow changes in absolute pressure levels. The mechano-electric principle of changes in fluid pressure proposed by Moskalenko (1959) reproduces the form of the pulsatile fluctuations fairly accurately, is very sensitive and linear, but cannot be used in the presence of vibrations. Strain-gauge manometers make use of the fact that the ohmic resistance of certain metals is proportional to their flection caused by pressure. Commercially produced strain-gauge manometers of various types can be attached to the manometer membrane (Liberman, 1958; Antonov et al., 1961; and others).

In manometers of the inductive type, the membrane is tightly connected to the mobile core of the coil. Its movement causes changes in the inductive resistance of the coil (Fig. 3). Such devices are widely used to record fluid pressure experimentally and clinically (Bering, 1955; Lundberg, 1960; Gilland, 1962; Sergienko,