raised intracranial andcerebral bloodflow · intracranial pressure wasraised to levels of...

Journal of Neurology, Neurosurgery, and Psychiatry, 1974, 37, 392-402

Raised intracranial pressure and cerebral blood flow3. Venous outflow tract pressures and vascular resistances in

experimental intracranial hypertensionI. H. JOHNSTON AND J. 0. ROWAN

From the Medical Research Council Cerebral Circulation Research Group at the Institute of NeurologicalSciences, Glasgow, and the Wellcome Surgical Research Institute, University of Glasgow

SYNOPSIS Pressure changes within the venous outflow tract from the brain were studied inanaesthetized baboons. Segmental vascular resistance changes were also calculated and the resultscorrelated with the changes in cerebral blood flow, measured by the 133Xenon clearance method.Three different methods were used to raise intracranial pressure: cisterna magna infusion, a supra-tentorial subdural balloon, and an infratentorial subdural balloon. A close correlation was foundbetween the cortical vein pressure and intracranial pressure with all methods of raising intracranialpressure: the overall correlation coefficient was 0-98. In the majority of animals sagittal sinuspressure showed little change through a wide range of intracranial pressure. In three of the sixanimals in the cisterna magna infusion group, however, sagittal sinus pressure increased to levelsapproaching the intracranial pressure during the later stages of intracranial hypertension. Jugularvenous pressure showed little change with increasing intracranial pressure. The relationship betweencerebral perfusion pressure and cerebral blood flow differed according to the method of increasingintracranial pressure. This was due to differing patterns of change in prevenous vascular resistance asvenous resistance increased progressively with increasing pressure in all three groups. The presentresults confirm, therefore, the validity of the current definition of cerebral perfusion pressure-that is,cerebral perfusion pressure is equal to mean arterial pressure minus mean intracranial pressure-bydemonstrating that intracranial pressure does represent the effective cerebral venous outflow pressure.

Raised intracranial pressure is known to cause areduction in cerebral blood flow, although thequantitative aspects of the relationship remainpoorly defined. Attempts have been made toestablish a correlation between perfusion pres-sure and blood flow and to identify critical levelsof perfusion pressure below which blood flowbegins to fall (Zwetnow, 1968, 1970). Bothclinical and experimental observations have,however, shown that no such direct relationshipexists (Miller et al., 1972; Johnston et al., 1972,1973). This may reflect the inadequacy of thepresent definition of cerebral perfusion pressureor dependence of the nature of vascular resist-ance changes on the type of increase in intra-cranial pressure.The aim of the present study has been to

measure directly the pressure changes occurringin different segments of the venous outflow tractfrom the brain when the intracranial pressure is

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raised in various ways. Thus the validity of thedefinition of cerebral perfusion pressure as meanarterial pressure minus mean intracranial pres-sure can be examined by determining whetherintracranial pressure accurately represents theeffective venous outflow pressure in differentcircumstances. At the same time, the changes invascular resistance can be calculated and thenature of these changes related to the varyingeffect on cerebral blood flow of the differentforms of intracranial hypertension seen in theearlier studies.

METHODS

Thirteen baboons, weighing between 8 and 13 kg,were used. Anaesthesia was induced with phencycli-dine hydrochloride (10 mg intramuscularly) andthiopentone sodium (60 mg intramuscularly) andmaintained with phencyclidine hydrochloride andnitrous oxide/oxygen mixture. The animals were

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Raised intracranial pressure and cerebral bloodflow

paralysed with suxamethonium chloride and ventila-tion was controlled using a Starling pump deliveringa tidal volume adjusted according to end-tidal CO2and arterial blood gas levels.The following parameters were measured:

CEREBRAL BLOOD FLOW (CBF) A polyethylene can-nula was placed in the proximal stump of the rightlingual artery after ligation of the right externalcarotid artery. Serial measurements of blood flowwere made using a slug injection of the radioisotope133Xenon dissolved in 0-45 to 0-55 ml. 0.900 saline at37.40 C. The rate of clearance of gamma activity wasmonitored using a collimated 1 in. sodium iodidecrystal scintillation detector placed over the rightparietal region. Cerebral blood flow was calculatedboth from the initial slope of the clearance curve andfrom the ratio of peak height to the area under thecurve. In addition, carotid artery blood flow wasmonitored continuously, using an electromagneticflow probe of 2-5 to 3 5 mm diameter (Nycotron) onthe exposed right common carotid artery.

VENOUS OUTFLOW TRACT PRESSURES The followingpressures were measured continuously by means ofindwelling catheters inserted as described below andconnected to strain gauge transducers.

Cortical vein pressure (Co VP) A small craniectomy,extending from the midline immediately behind thecoronal suture was made on the right side. A duralflap was reflected, hinged medially, to expose one ofthe large cortical veins in the area of entry into thesuperior sagittal sinus. Using the Zeiss operatingmicroscope the vein was freed of arachnoid mem-brane for 1-2 mm, a small incision was made in thevein wall, and a fine polyethylene catheter insertedfor a distance of 1-2 cm, directed away from themidline. The placement of the catheter in the veinwas checked by irrigating with small volumes of0-9%4 saline under vision and also by observing back-flow of venous blood into the catheter. The catheterwas secured to the dura mater with a suture and tothe cranium with dental cement. The dural incisionwas closed around the catheter with a continuoussuture.

Superior sagittal sinus pressure (SSP) A fine poly-ethylene catheter was inserted into the superiorsagittal sinus through a needle puncture 2 cm behindthe bregma and the catheter threaded a further 2 cmalong the sinus towards the torcular.

Jugular bulb pressure (JVP) A polyethylene catheterwas inserted in retrograde fashion, into the jugular

bulb from the exposed internal jugular vein in theneck.The craniectomy defect was sealed using dental

cement.

OTHER PARAMETERS Ventricularfluidpressure (VFP)was measured using a polyethylene cannula insertedinto the frontal horn of the right lateral ventricle viaa twist drill hole on the coronal suture 1 cm lateral tothe bregma.

Cisterna magna pressure (CMP) was measured insome experiments using a polyethylene cannulainserted by puncture of the atlantooccipital mem-brane under direct vision.

Arterial blood pressure (BP) was measured from thecatheter in the right lingual artery. In some experi-ments, when a poor tracing was obtained from thiscatheter due to damping, arterial pressure wasmeasured from a catheter inserted into the abdominalaorta via the left femoral artery.

End tidal C02 was continuously monitored using aninfrared analyser (Capnograph).

Arterial blood gases (PO2, pCO2, and pH) wereestimated at frequent intervals, as were sagittal sinusP02 and pH, using direct reading electrodes (Radio-meter).

Venous PCV and Hb were estimated at frequentintervals.

Intracranial pressure was raised in one of threedifferent ways: (1) by infusion of mock cerebrospinalfluid (CSF), at constant temperature, into the cisternamagna (six animals); (2) by expansion of a supra-tentorial subdural balloon in the right parietalregion (six animals); and (3) by expansion of aninfratentorial subdural balloon in the right cerebello-pontine angle (one animal). In each group of experi-ments the pressure was raised in increments of 10-20mmHg at approximately 30 minute intervals.

RESULTS

PRESSURE CHANGES Cortical vein pressure Themean control values for all measured variablesare shown in Table 1. With infusion of fluid intothe cisterna magna, cortical vein pressure roseprogressively with increasing intracranial pres-sure up to extreme levels of intracranial hyper-tension. The linearity of the relationship isshown in Fig. 1 a in which cortical vein pressuresare plotted against intracranial pressures for all

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TABLE 1MEAN CONTROL VALUE3 AND MEAN VALUES AT MAXIMUM INTRACRANIAL PRESSURE IN EACH OF THE THREE GROUPS

ICP Co VP SSP J VP BP CPP CBF

Cisterna magna infusionControl 9.1 11 4 4-8 3-6 90 7 81-8 41-5At max. ICP 114-3 113-4 43-6 6-3 129-7 15 0 11-5

Supratentorial balloonControl 5-6 9 1 8-3 4 5 71 2 64-2 49 0At max. ICP 74-3 77-7 11-2 3-8 91-3 17-0 15.0

Infratentorial balloonControl 11 7 17-0 -- - 75 3 63-7 38-9At max. ICP 47-0 51-0 - - 1330 86-0 66-0

(All values in mmHg except CBF, ml/100 g/min.)

coVpmmHg

ICP mmHg ICP mmHg

(a) (b)ICP mmHg

(c)

FIG. 1. Cortical vein pressures during increased intracranial pressure. (a) Cisterna magna infusion. (b) Supra-tentorial subdural balloon. (c) Infratentorial subdural balloon. Data from all experiments in each group.

TABLE 2SUMMARY OF CORRELATIONS BETWEEN CORTICAL VEINPRESSURE AND INTRACRANIAL PRESSURE FOR EACH METHOD

OF RAISING INTRACRANIAL PRESSURE

Type of ICP Regression Correla- t p Sy nincrease equation tion

coefficient

Cisternamagnainfusion y= 103x+ 28 0-98 32 '40001 7 95 39

Supratentorialballoon y=0 905x+2-7 0 97 22 40001 6 58 33

Infratentorialballoon y=0-89x+6-9 0-96 10 40 001 2-88 14

All y=0 997x+2 5 0 98 41 40 001 6-75 86

simultaneous measurements of the two pressuresin the cisterna magna infusion experiments. Thecorrelation coefficient, 0-98, is highly significantand the regression line closely parallel to the lineof identity. The positive intercept on the corticalvenous pressure axis, at 2-8 mmHg, reflects thetendency of vein pressure to remain slightlyhigher than intracranial pressure. A similar,linear, relationship between cortical vein pres-sure and intracranial pressure was also seenwhen the latter was increased by expansion ofeither a supratentorial or infratentorial balloon(Figs lb, c). The data from all three methods ofincreasing intracranial pressure are summarized

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SUPRATENTORIAL BALLOON

------ -

I. n - n --.-- --

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I nin

FIG. 2. Correspondence of transient changes in cortical vein pressure and intracranial pressure(supratentorial balloon). First arrow indicates balloon expansion, second arrow indicates range

change on recorder to 120-20 mmHg.

in Table 2. Transient induced changes in intra-cranial pressure were also closely mirrored bysimilar changes in cortical vein pressure (Fig. 2).A positive pressure gradient existed between

cortical vein and superior sagittal sinus undercontrol conditions. This gradient increased pro-

gressively with all methods of raising intracranialpressure, although the magnitude of the increasewas much less in three animals in the cisternamagna infusion group in which a progressiverise in sagittal sinus pressure occurred. In theseanimals sinus pressure rose to the level of corticalvein pressure for a short time, during the laterstages of intracranial hypertension.

Superior sagittal sinus pressure Mean controlvalues for all three groups are given in Table 1.With cisterna magna infusion two distinct typesof response were seen. In three out of six animalssagittal sinus pressure rose only slightly as the

intracranial pressure was raised to levels ofapproximately 40 mmHg. At this point sagittalsinus pressure began to rise rapidly and pro-gressively as intracranial pressure was further in-creased to reach maximum levels of 60, 80, and118 mmHg at intracranial pressure levels of 94,112, and 111 mmHg respectively. In these threeanimals, during the later stages of intracranialhypertension, transient changes in sagittal sinuspressure were also seen. These changes wereoften of considerable magnitude and wereapparently independent of changes in any of theother measured variables (Fig. 3). In the otherthree animals in the cisterna magna infusiongroup sagittal sinus pressure remained lowthroughout and, although there was a slight riseduring the later stages of intracranial hyper-tension levels, the pressure always remained lessthan 20 mmHg. Small fluctuations in sinuspressure in these three animals were predomi-

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tentorial subdural balloon. Data from all experiments in each group.

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Raised intracranial pressure and cerebral blood flow

nantly reflections of changes in cerebral bloodflow as shown by the carotid artery flowmeter.The two different patterns of response areapparent from Fig. 4a, which is a summary ofall simultaneous measurements of sagittal sinusand intracranial pressure in the cisterna magnainfusion experiments.When intracranial pressure was raised by

expansion of either a supratentorial or an infra-tentorial subdural balloon, sagittal sinus pres-sure remained low throughout (Fig. 4b). Inaddition, there were no transient, apparentlyspontaneous, changes in sagittal sinus pressure ofthe type seen with cisterna magna infusion.A substantial gradient between sagittal sinus

and jugular bulb pressures was seen only inthose animals showing a marked increase insagittal sinus pressure during the later stages ofintracranial hypertension.

Jugular bulb pressure Mean control values areshown in Table 1. With cisterna magna infusionthere was a slight but progressive increase injugular bulb pressure as intracranial pressurewas increased. In the later stages of each experi-ment, however, jugular bulb pressure fell as botharterial blood pressure and cerebral blood flowfell. With expansion of either a supratentorial orinfratentorial balloon, there was little change injugular bulb pressure with increasing intracranialpressure: some animals showed a slight increase,others a slight decrease.

Blood pressure and cerebral perfusion pressureWith cisterna magna infusion all animals showeda marked increase in blood pressure, startingduring the initial stages of intracranial hyper-tension, reaching a maximum at intracranialpressure levels between 40 and 90 mmHg, thenfalling as intracranial pressure was further in-creased. Likewise, with both types of balloonthere was a blood pressure response, a transientresponse occurring with each addition of fluid tothe balloon, in addition to a sustained increaseover the course of each experiment. The magni-tude of the sustained response was, however,less than with cisterna magna infusion.

Changes in cerebral perfusion pressure,whether calculated as the difference betweenblood pressure and cortical vein pressure, orbetween blood pressure and jugular bulb pres-

sure depended largely on the time of onset andmagnitude of the blood pressure response. Withcisterna magna infusion cerebral perfusionpressure (blood pressure-cortical vein pressure)rose steadily in three of the six animals, reacheda maximum at intracranial pressure levels of 36,49, and 65 mmHg respectively, then fell pro-gressively as the intracranial pressure was furtherincreased. In the other three animals in thisgroup there was an early fall in cerebral perfu-sion pressure, at intracranial pressure levels of25, 29, and 41 mmHg, after which perfusionpressure returned to approximately controllevels as intracranial pressure was further in-creased. In all six experiments in this groupcerebral perfusion pressure fell in the laterstages, as the blood pressure fell progressively.With the supratentorial subdural balloon

changes in cerebral perfusion pressure (bloodpressure-cortical vein pressure) were more uni-form. Values remained around control levels upto intracranial pressure levels from 38-93mmHg, then fell as intracranial pressure was in-creased beyond these levels. There was no rangeof intracranial pressure during which perfusionpressure tended to be greater than control levels.

If cerebral perfusion pressure was calculatedas the difference between blood pressure andjugular bulb pressure, there was also a differentresponse according to the way in which intra-cranial pressure was increased. With cisternamagna infusion perfusion pressure increasedwith the initial increases in intracranial pressure,then remained well above control levels as intra-cranial pressure was further increased. With thesupratentorial balloon there was also an initialincrease in perfusion pressure of smaller magni-tude, after which perfusion pressure remainedwithin a relatively narrow range, only slightlygreater than the control range, as intracranialpressure was further increased.

RESISTANCE CHANGES When cerebrovascularresistance was calculated as the ratio of cerebralperfusion pressure to cerebral blood flow therewas considerable variation in the changes in thecisterna magna infusion group. In two of the sixanimals cerebrovascular resistance fell pro-gressively with increasing intracranial pressure.In the remaining four animals the level of vascu-lar resistance varied considerably. The different

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FIG. 5. Mean values for cerebral perfusion pressure (CPP), cerebral bloodflow (CBF) and segmenital vascularresistanice (total resistance Rt, arterial resistance Ra, and venous resistance Rv), for 10 n1mHg ranges ofintracranial pressure. (a) Cisterna magna infusiont. (b) Supratentorial subdural balloon.

patterns of response did not coincide withdifferences in the blood flow response, althoughthe two animals showing a progressive fall incerebrovascular resistance were those in whomthe superior sagittal sinus pressure remained lowthroughout.With the supratentorial subdural balloon,

changes in cerebrovascular resistance were more

uniform, five of the six animals showing an

initially steady level, followed by a slight, butprogressive fall. In the sixth animal vascularresistance started to fall with the first increase inintracranial pressure, but then rose slightly to-wards the end of the experiment.When arterial and venous resistances were

calculated separately a more uniform pictureemerged. With cisterna magna infusion all ani-mals showed a progressive increase in venousresistance with increasing intracranial pressure(Fig. 5a). In three of the six animals, the majorlocus of venous resistance remained betweencortical vein and sagittal sinus, whereas in the

other three animals the main venous resistanceshifted to the sagittal sinus during the latterstages of intracranial hypertension. In all sixanimals the arterial resistance tended to fall pro-gressively (Fig. 5a).With the supratentorial subdural balloon a

different type of response was seen. Whereas a

progressive increase in venous resistance, similarto that seen with cisterna magna infusion, didoccur (Fig. Sb), the major locus of resistance re-

mained between the cortical veins and the sagittalsinus in all instances. The main contrast was,however, provided by the arterial resistancewhich showed much less tendency to fall withincreasing intracranial pressure when comparedwith the cisterna magna infusion group (Fig. 5b).

BLOOD FLOW CHANGES Control values for eachgroup are shown in Table 1. The basic patternsof response were similar to those described indetail in the earlier studies (Johnston et al., 1972,1973). In addition, the relationships between

CPP

CBF

CVR

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TABLE 3VALUES FOR CEREBRAL BLOOD FLOW (CBF), CEREBRAL PERFUSION PRESSURE (CPP), AND SEGMENTAL VASCULAR RESISTANCE,AT CONTROL LEVELS AND AT MAXIMUM CEREBRAL BLOOD FLOW, FOR INDIVIDUAL EXPERIMENTS IN CISTERNA MAGNA

INFUSION GROUP

Expt. CBF CPP Rt Ra Rv CBF CPP Rt Ra Rv(ml./100 glmin) (mmHg) (ml./100 glmin) (mmHg)

1 28 72 2-88 2-44 0 40 39 76 2-56 1-82 0 742 46 79 1*86 1*74 0 12 61 98 2 54 1-47 1 073 42 66 1-73 1 52 0-21 71 103 2-21 1-24 0974 56 99 1-90 1 55 035 83 98 1-80 0-96 0-845 45 84 1*91 1*87 0 04 55 121 3-01 2-12 0-896 39 87 2-22 - - 110 81 0-74 - -Mean 42-7 81-2 2-08 1-82 0-22 69-8 96-2 2-14 1-52 0 90SD 9-2 11-65 0-42 0 37 0-15 24-6 16-2 0-80 0-46 0 13

blood flow and perfusion pressure (bloodpressure minus cortical vein pressure) were thesame as those described earlier, there being adifferent relationship with each method of raisingthe intracranial pressure. The period of hyperae-mia seen with cisterna magna infusion wasassociated in three out of six animals, with anincrease in cerebral perfusion pressure. In two ofthese three animals arterial resistance fellslightly, while in the others it increased. In theother three animals in this group cerebral perfu-sion pressure was at approximately controllevels at the time of maximum hyperaemiawhich was associated with a marked fall inarterial resistance (Table 3).

DISCUSSION

In trying to explain why different ways of raisingintracranial pressure lead to different patterns ofchange in cerebral blood flow, and quite distinctrelationships between cerebral perfusion pres-sure and blood flow, two factors are important.Firstly, it is necessary to examine the validity ofthe current concept of cerebral perfusion pres-sure. Secondly, the nature of the vascularresistance changes occurring in the differentforms of intracranial hypertension must be moreclearly understood. To meet these requirements,it was decided to extend the existing observationon intracranial venous outflow tract pressures,since direct measurements of cortical veinpressures had not been made over a wide rangeof intracranial pressure and observations onsagittal sinus pressure changes have been quiteconflicting. Apart from elucidating the vari-ability in blood flow changes referred to above,

direct pressure measurements in various seg-ments of the venous outflow tract might, it wasthought, provide information about other aspectsof brain function affected by raised intracranialpressure.The present results clearly show that the

pressure within the large cortical veins rises pro-gressively with increasing intracranial pressure,in linear fashion, with vein pressures tending toremain at slightly higher levels than intracranialpressures. These findings are in accord with theearlier studies that cortical vein pressure in thelower ranges of intracranial pressure is in-creased (Shulman, 1965; Shulman and Verdier,1967). A slight positive differential between thetwo pressures is, of course, essential in maintain-ing the patency of the veins.The pressure within the posterior part of the

superior sagittal sinus showed a less uniformresponse with progressive intracranial hyper-tension. With cisterna magna infusion a numberof animals showed a considerable rise in sinuspressure, starting at intracranial pressure levelsaround 40 mmHg and continuing as intra-cranial pressure was further increased. Otheranimals in the same group did not show this in-crease in sinus pressure, nor did any of theanimals in the other two groups. Those animalsin which sinus pressure rose markedly showedlarge transient fluctuations in pressure unrelatedto changes in any of the other measured pres-sures. These have not been described previouslyand may represent intermittent opening andclosing of the lumen of the sinus under theinfluence of the surrounding intracranial pres-sure.

In attempting to relate the present observa-

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tions on sagittal sinus pressure changes to pre-vious findings it is difficult to achieve a satisfac-tory synthesis. Under normal conditions thepressure within the sinus would be expected to beless than the intracranial pressure and to dependlargely on the right atrial pressure (Davson,1967). This has been confirmed, both by directmeasurement and by other methods (Wegefarth,1914; Weed and Flexner, 1933; Bedford, 1942;Shulman et al., 1964). Observations during in-creased intracranial pressure have, however,given quite variable results. Some studies haveshown little change in sagittal sinus pressure(Becht, 1920; Weed and Flexner, 1933), somehave shown a decrease in sinus pressure (Wright,1938; Bedford, 1942), while others have shownan increase in sagittal sinus pressure with in-creasing intracranial pressure (Dixon and Hali-burton, 1914; Langfitt et al., 1966). Clinicalmeasurements in acute intracranial hypertensionand both clinical and experimental observationsin chronic intracranial hypertension have alsoshown that sagittal sinus pressure may rise withincreasing intracranial pressure (Shulman et al.,1964; Kinal, 1966; Osterholm, 1970). It seemsprobable that the pressure within the sagittalsinus reflects the sum of several variables inclu-ding mechanical factors affecting sinus com-pressibility, the level of blood flow through thesinus, and the central venous pressure. The rela-tive importance of each factor may, in turn, de-pend on the exact site of measurement, thespecies studied, and the method of increasingintracranial pressure which will act throughdifferences both in local distorting forces andblood flow levels.

In the present study jugular bulb pressureshowed little variation whatever method wasused to raise intracranial pressure, findings whichagree with earlier reports of both jugular bulband torcular pressures (Bedford, 1942; Langfittet al., 1966). Any changes which do occur injugular bulb pressure will depend on a combina-tion of changes in central venous pressuresecondary to the effects of raised intracranialpressure on cardiovascular function (Brown,1956) and on the level of cerebral bloodflow.Some of the main aspects of brain function

which may be influenced by these changes inintracranial venous pressures include cerebral

blood flow, capillary filtration, and CSFcirculation.

Initial studies of cerebral blood flow in raisedintracranial pressure attempted to relate levels ofblood flow directly to levels of intracranialpressure (Kety et al., 1948; Noell and Schneider,1948). More recently, cerebral perfusion pressurehas been put forward as the major determinantof cerebral blood flow (Zwetnow, 1968; Haggen-dal et al., 1970; Zwetnow, 1970). If a clearrelation between either intracranial pressure, orcerebral perfusion pressure, and cerebral bloodflow could be established it would have obviousvalue for the clinician who, being able tomeasure these pressures, could predict whatchanges in cerebral blood flow might be occur-ring in different clinical circumstances. Bothclinical and experimental studies, referred toearlier (Miller et al., 1971; Johnston et al., 1972,1973), have clearly shown, however, that no suchdirect relationship can be defined. This may bedue both to the shortcomings of the presentdefinition of cerebral perfusion pressure and tothe variable patterns of resistance change whichmay occur in different forms of intracranialhypertension.The close correspondence between cortical

vein and intracranial pressures in the presentstudy establishes the validity of the assumptionthat intracranial pressure represents the effectivevenous outflow pressure through a wide range ofintracranial pressure. Providing that there is noappreciable change in the magnitude of thepressure drop between the major extracranialarteries and their intracranial extensions, thepresent definition of cerebral perfusion pressureis acceptable (Kanzow and Dieckhoff, 1969). Itis, therefore, to the different patterns of responseof the intracranial vascular resistance that atten-tion must be directed in an attempt to explainthe variability of cerebral blood flow in differentforms of intracranial hypertension.With measurements of intravascular pressures

at a series of points and assuming a uniformityof flow through each section, it is possible tocalculate segmental resistances for the bloodvessels supplying and draining the brain. Suchcalculations show a progressive increase invenous resistance with increasing intracranialpressure with the major locus of resistance be-tween cortical veins and superior sagittal sinus.

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The uniformity of the direction of changes invenous resistance regardless of the method usedto raise intracranial pressure suggests that it isdifferences in the prevenous resistance whichdetermine the different patterns of change incerebral blood flow. Calculated values supportthis view showing, for example, a marked fall inarterial resistance when intracranial pressure israised by cisterna magna infusion, whereas witha supratentorial balloon arterial resistance tendsto remain relatively high.What is not clear, however, is how such

differences in behaviour in the prevenous resist-ance vessels are brought about, although this isof central importance to an understanding ofautoregulation in the cerebral circulation.Various theories have been proposed to explainautoregulation, metabolic, myogenic, neuro-genic, and tissue pressure hypotheses (Green etal., 1964), yet the matter remains unresolved.The present studies do not permit any distinctionbetween the extant theories. All that can be saidis that, while changes in venous resistance appearto depend directly on the level of intracranialpressure, changes in prevenous resistance varyaccording to the way in which the intracranialpressure is increased.Another factor which will clearly be influenced

by alterations in cortical venous pressure iscapillary filtration within brain tissue. The rateof net transcapillary fluid movement will dependon the factors originally defined by Starling,which include the hydrostatic capillary and inter-stitial fluid pressures, the colloid osmotic pres-sures of plasma and interstitial fluid, and thecapillary filtration coefficient (Mellander andJohansson, 1968). The hydrostatic capillarypressure will, in turn, depend on arterial inflowand venous outflow pressures as well as the ratiobetween post and pre-capillary resistances(Pappenheimer and Soto-Rivera, 1948), whilethe interstitial fluid pressure will depend on theintracranial pressure. If these values are calcu-lated from the present data it is apparent thatthere is a progressive increase in hydrostaticcapillary pressure, which, although partlycounterbalanced by the increase in interstitialfluid pressure would lead to an increase in netcapillary filtration, if changes in colloid osmoticpressures can be neglected. Such changes offer anexplanation of the progressive brain swelling

which accompanies sustained intracranial hyper-tension.As a compensatory mechanism there is, how-

ever, a change in the pressure differential,thought to control the transfer of CSF from sub-arachnoid space to venous sinus (Davson, 1967;Davson et al., 1970). Thus, in the present experi-ments, a progressive increase occurred in thepressure gradient between the subarachnoidspace and the superior sagittal sinus. Even inthose experiments where sagittal sinus pressureincreased markedly, a significant gradient wasstill maintained in all but one instance.

In summary, therefore, a number of pointsemerge from the study of segmental pressurechanges in the brain vasculature during raisedintracranial pressure. It is clear, firstly, that aprogressive increase in intracranial pressure willresult in a similar increase in cortical veinpressure with the vein pressures staying slightlyabove the ambient intracranial pressure, therebypreserving the patency of the veins. In themajority of instances neither sagittal sinus norjugular bulb pressures change appreciably,although sinus pressure may show a marked in-crease when intracranial pressure is raised bycisterna magna infusion. These findings meanthat the current definition of cerebral perfusionpressure is valid, provided that the magnitude ofthe pressure drop between extracranial and intra-cranial arteries does not alter significantly asintracranial pressure is increased. A corollary ofthese findings is that there is a progressive in-crease in intracranial venous resistance with in-creasing intracranial pressure which is inde-pendent of the way in which the intracranialpressure is raised, but directly related to thelevel of pressure. The differences in blood flowseen with different types of intracranial hyper-tension depend, therefore, on variations in theresponse of the prevenous resistance, althoughthe mechanism underlying such variations is notunderstood. The changes occurring in intra-vascular and extravascular pressures will alsoresult in a net increase in transcapillary fluidmovement from blood to brain, with increasingintracranial pressure. There will be, however, acompensatory increase in the pressure differen-tial favouring transfer of CSF from subarach-noid space to venous sinus, as intracranialpressure is increased.

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Finally, from the clinician's standpoint, thesefindings establish the validity of the currentdefinition of cerebral perfusion pressure, while atthe same time showing that clinical measure-ments of intracranial perfusion pressure do notallow conclusions to be drawn about the level ofcerebral blood flow in individual cases.

The authors wish to thank Professor W. B. Jennettand Dr. A. M. Harper for their advice and assistancethroughout this study. Our thanks are also due to thetechnical staff of the Wellcome Surgical ResearchInstitute.

REFERENCES

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