Cerebral Blood Flow Determined by Hydrogen
Clearance During Middle Cerebral Artery
Occlusion in Unanesthetized Monkeys
R.
B. MORAWETZ, M.D.,
R. G.
OJEMANN, M.D.,
AND R.
U. DEGIROLAMI,
F. W.
M. CROWELL,
MARCOUX,
143
M.D.,
B.S.,
M.D.
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SUMMARY Unanesthetized macaque monkeys were subjected to
middle cerebral artery (MCA) occlusion. Local cerebral blood flow
(ICBF) was measured with a hydrogen clearance technique. Mean
arterial blood pressure, arterial blood gases, and intracranial
pressure were monitored serially. Two weeks after ischemic insult, a
neuropathologic examination documented cerebral infarction and its
relation to CBF recording sites.
Unanesthetized monkeys hyperventilated and became hypocapneic,
particularly after MCA occlusion (mean Paco 2 fell from 33 to 26
mm Hg). Intracranial pressure remained normal except in massive
fatal infarction, where it rose dramatically.
Responses to MCA occlusion were strikingly variable; some
animals showed little ICBF reduction and no deficit or infarction,
while others sustained marked ICBF reduction with hemiplegia and
massive fatal infarction. Extent of ICBF reduction correlated well
with infarct size. Since the extent of ICBF reduction reflects
collateral circulation, variation in collateral supply appears responsible for variation of infarction.
Re-opening of MCA occlusion always led to restoration of normal
or above normal ICBF. Thus, no evidence for impaired reperfusion
was observed. Post-ischemic CBF markedly above normal was
associated with eventual severe infarction. Restoration of MCA flow
led to improvement of hemiparesis after moderate reduction in ICBF,
but fatal infarction occurred despite restored flow after severe reduction in ICBF. "No reflow" was not observed.
When ICBF fell below 12cc/100gm/min for 2 hours or longer,
local infarction resulted. Flow above this infarction threshold
prevented irreversible damage.
IMPROVED THERAPY for ischemic strokes will depend
on enhanced understanding of their pathophysiology. In particular, the defining characteristics of irreversible damage 12
need to be identified, since treatment will be most useful only
before reversible changes become permanent. Some function
of cerebral blood flow (CBF) reduction and its duration
probably defines a threshold for irreversible infarction. In
turn, the extent of CBF reduction after cerebrovascular
occlusion likely reflects the availability of collateral circulation.1
An animal model offers the best opportunity to examine
the CBF threshold for irreversible damage after cerebrovascular occlusion. To be most useful, such a stroke model
must (1) use a cerebrovascular system similar to that of
man,1'3"4 (2) avoid the unphysiologic effects of anesthesia,4"8 (3) monitor ischemia-modifying variables such as
blood pressure and blood gases,7 (4) monitor sequential
changes in local CBF following occlusion, 1 ' 7 " (5) assess
ischemic change by neurologic examination and irreversible
damage by morphologic evaluation,4"5 and (6) utilize temporary occlusion to determine maximum tolerable occlusion
time. 34
We report here a pilot study in an animal model designed
to meet these criteria. In unanesthetized Macaca irus
monkeys, the middle cerebral artery (MCA) was occluded
temporarily. Arterial blood pressure and blood gases were
monitored. Serial measurements of local CBF (ICBF) were
made at 6 sites by hydrogen clearance. Neurologic status
was examined sequentially. Neuropathologic evaluation was
performed 2-3 weeks after MCA occlusion to identify infarction and its relation to sites of ICBF recording.
Results suggest the model is useful. Responses to MCA
occlusion varied strikingly, but extent of ICBF reduction
correlated well with infarct size. A threshold for infarction
was identified: when ICBF fell below 12cc/100g/min for 2
hours or longer, local infarction occurred.
From the Microneurosurgery Laboratory of the Neurosurgical Service,
Massachusetts General Hospital and Harvard Medical School, Boston, MA
02114.
Dr. Morawetz's present address is: Division of Neurosurgery, University of
Alabama Medical Center, Birmingham, AL 35294. Dr. DeGirolami's present address is: Department of Pathology (Neuropathology), University of
Massachusetts Medical Center, 55 Lake Ave. N., Worcester, MA 01605.
Supported in part by the National Institute of Neurological and Communicative Disorders and Stroke through grants NS 13165 and NS 10828,
and Teacher-Investigator Award NSI1001 to Dr. Crowell.
Methods
We studied 8 Macaca irus monkeys, unselected for sex
and weighing 3.5-4.5 kg. A preparatory operation was performed under general anesthesia to install an aortic catheter,
platinum electrodes for measurement of ICBF, epidural
transducers for measurement of ICP (intracranial pressure),
and a ligature around the right middle cerebral artery. After
surgery, the animal was placed in a standard primate
restraining chair. The following day, baseline data were
gathered, and the MCA ligature was tightened for intervals
of 120, 150 or 180 minutes (permanent occlusion in 1 case)
to produce temporary occlusion. Before and during occlusion and after deocclusion we monitored mean arterial
pressure, arterial blood gases, neurologic status, ICBF, and
intracranial pressure. ICBF was monitored immediately
after deocclusion, and at 24, 48, 72 hours, and 7, 10 and 14
days. In some cases late measurements were made. Fortyeight to 72 hours after occlusion the monkey was returned to
its cage. Neuropathologic evaluation utilizing horizontal
serial sections identified infarcts and their relation to ICBF
recording sites.
Technique of MCA Occlusion
Under phencyclidine anesthesia (Bio-ceutic Laboratories,
Inc., St. Joseph, MO) Macaca irus monkeys underwent
144
STROKE
right orbital exenteration and posterior orbital craniectomy
for exposure of the carotid bifurcation.9 Using the operating
microscope, a 10-0 nylon snare ligature was passed around
the right MCA at its origin and brought through the orbit
via a PE-10 polyethylene catheter (Clay Adams, Parsippany, NJ). The suture was then tied around an additional
short segment of PE-10 catheter, and the amount of traction
necessary for occlusion was determined.4 The orbit was
sealed with acrylic (Caulk Grip Cement, L.D. Caulk Co.,
Milford, DE) in watertight fashion, and periorbital tissues
were reapproximated. Twenty-four hours later 6 monkeys
were subjected to focal cerebral ischemia, and an additional
2 animals served as controls.
Local Cerebral Blood Flow
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1CBF was measured using a hydrogen clearance technique.8- " 13 Electrodes were made of 70% platinum 30%
iridium wire (Medwire Co., Mt. Vernon, NY), .010 inch in
diameter and Teflon-coated save for a 2mm bare tip. An
array of electrodes was placed stereotactically in the area
known to be ischemic after MCA occlusion." Five electrodes were implanted in the right posterior frontal region
with a sixth control electrode in the left posterior frontal
region. Electrode number 1 was placed in the globus pallidus
using stereotactic technique, and electrodes 2 through 5 were
placed at 2.5-3 mm intervals moving laterally in the right
hemisphere (see fig. 5). Electrode 6 (control) was placed in
the left hemisphere. A reference electrode was placed in the
anterior frontal skull. Extracranial microconnectors were
imbedded in acrylic and fixed to the skull; this arrangement
allowed the monkey to be returned to his cage between
determinations. Hydrogen gas (about 4%) was fed into a
plastic breathing chamber placed over the monkey's head. A
vacuum venting system permitted prompt evacuation of
hydrogen from the chamber at the cessation of hydrogen inhalation. Electrodes were polarized at + 0.65 volts according to a modification of the voltage clamp circuit of Willis et
al.13 The first 40 seconds of hydrogen washout were disregarded to avoid problems of recirculation.12
Other Monitoring Methods
Intracranial pressure (ICP) measurements were made
using a modification of the epidural pressure transducer
system described by O'Brien and Waltz.15 In each parietal
region an epidural pressure transducer was placed coplanar
to the dura and fixed to the skull. A pressure in the epidural
space of 0 mm of mercury was assumed for the normal
monkey in the upright position. Statham® Model P-23
transducers (Gould-Statham,® Hato Rey, PR) were used to
measure pressures. A femoro-aortic arterial line allowed
monitoring of mean arterial pressure and arterial blood gases. A Grass polygraph (model 7B, Grass Medical
Instruments, Quincy, MA) recorded 1CBF, blood pressure,
and ICP.
Observations During Focal Ischemia
On the day following preparatory surgery, we carried out
a neurological examination on the monkey in a restraining
chair. Baseline determinations were made for 1CBF, ICP,
mean arterial pressure and arterial blood gases. MCA occlu-
VOL. 9, No
2, MARCH-APRIL
1978
sion was then achieved by applying traction to the snare
ligature; traction was maintained with aneurysm clips. After
120-180 minutes of occlusion, ischemia was reversed by
releasing traction on the snare ligature. (A single animal underwent permanent MCA occlusion.)
Neuropathology
Monkeys which did not expire acutely were sacrificed 2-3
weeks after the onset of the ischemic insult. Monopolar
cauterization was applied to each electrode to help in identification of electrode tip sites. Brains were fixed in situ by
trans-cardiac perfusion with 10% phosphate-buffered formalin. The right internal carotid artery was catheterized in
the neck and injected with Mifcrofil® to document patency of
the right MCA at the point of temporary occlusion. In every
case the vessel was patent with the exception of the permanently occluded vessel. The brains were removed and immersed in the perfusion fixative for an additional 2 to 3
weeks. The brain stem was then severed at the midbrain and
the entire brain was embedded in celloidin. The whole brain
was then serially sectioned in the horizontal plane in 15
micron sections. The sections were sequentially identified
and stained in the following fashion: the first 8 sections were
segregated in a "stain bottle" and the subsequent 17 sections
were labelled "save." Sections from the "stain bottle" were
stained with hematoxylin and eosin, cresyl violet and Loyez
stain for myelin. The procedure was repeated for the entire
brain so that, in effect, sections available for microscopic
review were at 3.75 millimeter intervals. Sections were examined sequentially to locate the electrode tracts and tips
(cauterized tissue) and to identify size, location, and
character of infarction in relation to the electrodes.
Results
Systemic Factors
These monkeys showed variable levels of alertness, ranging from calm to agitated with vocalization and tail
movements. Moderate hypertension (cf. table 1) was
probably related to agitation. Likewise, agitation caused
hyperventilation and a persistent alkalotic hypocapnea,
which was more pronounced during and after MCA occlusion. Pao 2 measurements demonstrated normal oxygenation for all animals. Hematocrits tended to fall gradually
TABLE 1 Summary of Blood Gases, Blood Pressures and
Hemalocrils Before, During and After MCA Occlusion (where
applicable). Mean Values with Standard Deviations
Before
occlusion
During MCA
occlusion
After MCA
occlusion
MAP
(mm Hg)
Pao8
(mm Hg)
121
±12.8
96.4
±15.5
122
±14.7
110
± 9.6
93.4
± 9.6
89.0
±11.7
Pacoj
33.0
± 5.8
26.0
± 6.4
28.3
± 5.0
(mm Hg)
PH
±
Hct
%
7.43
.04
30.0
± 1.0
±
7.52
.04
28.5
± 4.6
±
7.44
.04
26.1
± 3.6
145
CBF DURING MCA OCCLUSION/A/orawefr et al.
over the study period (from a mean of 30% down to
probably related to frequent arterial blood gas sampling.
Local CBF Studies
ICBF studies generally produced monoexponential
washout curves, with occasional biexponential exceptions.
Baseline ICBF values for electrodes in basal ganglia or insula ranged from 34 to 101 cc/lOOg/min. Serial values of
ICBF from control electrodes varied up to ± 15% over the
2-3 week survival period.
Response to MCA Occlusion
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MCA occlusion led to a neurologic deficit within 3
minutes in all 6 animals. Five of the animals developed a
complete left facial paralysis, flaccid left upper limb distal to
the shoulder, markedly paretic left lower limb, with turning
of head and eyes to the right and unresponsiveness to threat
or food presented from the left. In 1 animal, MCA occlusion
produced only mild upper limb paresis.
MCA occlusion led to an immediate decrease in ipsilateral ICBF in all animals (table 2, figs. 1-3). Residual
flow at individual electrodes ranged from 9% to 107% of preocclusion values (average 42%). Residual flow in the most
lateral and medial electrodes tended to be slightly higher,
and, in a single instance, an elevated value was recorded
(107% in globus pallidus in Exp. 1). ICBF in the contralateral control electrode (caudate or putamen) rose in 5 of 6
animals, ranging from 95% to 167% of pre-occlusion values
(average 122%). In chronic infarcts, ICBF tended to fall over
the 2 week follow up interval (fig. 2).
During temporary MCA occlusion, neurologic status and
ICBF (2-3 determinations) remained stable. In the single
animal with permanent occlusion, mild left upper limb
paresis and diminished ICBF returned to normal by 24 hours
(fig. 1). Permanent occlusion in this animal was verified at
autopsy.
Response to MCA De-occlusion
After de-occlusion at 2-3 hours, 3 animals showed prompt
neurologic improvement, readily discernible within 30-60
minutes. Two monkeys (#3 and #6) with severe ischemia
(ICBF less than 15 ml/lOOg/min) improved promptly to a
moderate hemiparesis with further gradual improvement up
to the time of sacrifice (fig. 2). One monkey (#1) with
moderate ischemia (ICBF more than 15ml/100g/min) made
an immediate full recovery (fig. 1). After de-occlusion in
these animals, ICBF rose to levels above normal at most
electrodes and ICP remained normal.
Two monkeys (#4 and #5) with profound focal ischemia
(less than 5ml/100g/min) showed no improvement after deocclusion but instead develbped progressive drowsiness with
death at 24 and 72 hours (fig. 3). These were the only
monkeys sustaining slight subarachnoid hemorrhage during
ligature placement. Both animals demonstrated marked
reactive hyperemia, which appeared immediately in 1 and at
24 hours in the other. The latter monkey demonstrated a
marked terminal rise in ICP (> 1000 mm water). Animals
not expiring acutely (#1-3 and #6) showed no rise in ICP.
Neuropathologic findings
Serial horizontal sections through all the brains allowed
precise mapping of the electrode tracts (fig. 5).
Distinguishing between infarcted tissue and cauterization
necrosis was sometimes difficult — impossible in 1 animal
that died acutely (#4). In general, electrode 1 lay in the internal capsule, 2 in the putamen, 3 and 4 in the insular white
matter, 5 in the insular cortex and 6 in the contralateral
putamen (table 2).
Histopathological changes were typical of ischemic infarcts of 2 weeks duration (fig. 5), with the exception of Experiment #5 in which a hemorrhagic infarct was found, and
Experiment #4, where acute ischemic infarction was present.
Infarcts varied in size and location: Experiment #1 showed
TABLE 2 Summary Chart Showing Duration of Occlusion, Clinical Findings, Electrode Site, Flow During
MCA Occlusion, and Pathology for Each Monkey
Exp.
no.
Duration of
ischemia (min)
1
120
2
3
4
5
6
Clinical response
Hemiparesis during occlusion, complete resolution
after de-occlusion
Electrode
Site*
CBF
ml/lOOgm/min.
Infarct
Permanent Transient mild hemiparesis,
Site
complete resolution
CBF
Infarct
Hemiparesis during occlu188
Site
sion, partial resolution
CBF
Infarct
Hemiplegia, no improve123
Site
ment; death at 72 hrs.
CBF
Infarct
Hemiplegia, no improve126
Site
ment; death at 24 hrs.
CBF
Infarct
Hemiplegia, partial
157
Site
resolution
CBF
Infarct
ICBF and Pathology
2
3
4
5
GP
P
I
I
CX
40
0
AIC
26
27
0
P
40
0
P
11.5
36
0
P
31
0
I
25
-j-
±
P
4
38
0
I
49
0
I
14
0
I
3
-fI
5
+ (hem)
I
43
0
CX
43
0
CX
12
0
CX
3
1
d=
AIC
6
AIC
9
-f?
15
0
AIC
10
?
14
0
P
8
P
3
-fP
5
+ (hem)
I
10
+
+
+
-j-
0
+
CX
13
?
CX
42
0
•Abbreviations: GP =' globus pallidus; P = putamen; I = insular white matter; CX sa insular cortex and AIC - anterior limb
VOL 9, No 2, MARCH-APRIL
STROKE
146
1978
Electrode
120
»—••»
no
•
100
2
•
3
t>—a
4
5
6
90
so
70
60
50
40
30
20
10
0
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-Ui
j i
PRE- ^ T " | M M E - 24hrs
occ
OCC.
11
48 hrs
(2 hrs.)
20
72 hrs
FIGURE 1. Good collateral supply — no infarction. Above: (Monkey #1}: Hemiparesis
during two-hour ischemia. Full recovery after
deocclusion and no infarction.
Below:
(Monkey #2): Minimal hemiparesis and
modest ischemia early after permanent occlusion. Recovery in 24 hours and no infarction.
7d 10d 14doys
DIATE
POST-OCCLUSION
-
II
PREOCCLUSION
DAY OF
OCCLUSION
PERMANENT
OCCLUSION
24hrs
4Bhrs
JL_T
72hrs
JL
^
todays (5boys
POST-OCCLUSION
an infarct 50-75 microns in diameter in the deep gray matter
of the globus pallidus distant from the electrode tips. Experiment §2 showed an hourglass-shaped infarct in the anterior
limb of the internal capsule and deep medial globus pallidus.
This 100 micron infarct came close to electrode 1 but did not
touch it. Experiment #3 showed an infarct less than 1 cm in
diameter involving electrodes 2, 3, and 4. Experiment #4
showed acute infarction of the entire territory of the middle
cerebral artery with massive edema and poor localization of
the electrode tips. Experiment #5 showed a 2 cm hemorrhagic infarct with extension to insular cortex and poor electrode localization. Experiment #6 showed a 1.5 cm. ischemic
infarct surrounding electrodes 1 and 2 and adjacent to electrode 3.
Physio-pathologic Correlations
1CBF during MCA occlusion correlated closely with infarct size. The greater the residual 1CBF (which can only
come from collateral circulation), the smaller the infarct
(see table 2). In animals with good collateral circulation (#1
and #2, fig. 1), 2 hours and permanent occlusion led to little
or no infarction. In animals with moderate collateral (#3 and
#6, fig. 2), 2-3 hour occlusion caused medium-sized infarction. In animals with poor collateral (#4 and #5, fig. 3), 2
hour occlusion produced massive fatal infarction.
When 1CBF during MCA occlusion remained above
12cc/100g/min, tissue around the recording electrode
showed no infarction (see fig. 4). (Two exceptions involved
electrodes which lay on the edge of an infarction and thus
may have recorded higher flow from nearby preserved
tissue.) When residual 1CBF fell below 12cc/100g/min for 2
hours or more, infarction invariably occurred around the
electrode tip. In our animals, the infarction threshold was
about 30% of pre-occlusion 1CBF. No definite correlation
could be drawn between hemorrhagic infarction and 1CBF
values.
CBF DURING MCA OCCLUSION/A/oraw/z et al.
147
120
110
100
90
eo
\
70
§
60
5
\°
<J
40
30
20
10
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oL
PREOCCLUSION
" T " Immediate
OCCLUSION
(188 nun.)
T2hrs 8doys22*jys
POST-OCCLUSION
FIGURE 2. Moderate collateral supply —
moderate infarction. Above: (Monkey §3):
Marked hemiparesis during 3-hour severe
ischemia. Partial recovery after deocclusion
and moderate infarction. Below: {Monkey §6):
Marked hemiparesis during 2'A hour severe
ischemia. Partial recovery after deocclusion
and moderate infarction.
120
110
100
90
i
80
70
60
50
40
30
20
10
0
24 hrs PRIOR PRE- T *
toOCC.
IMME-
OCC.^^DIATE
24hrs
1
48hrs
72 hrs
1
6 Days
POST-OCCLUSION
Discussion
Unanesthetized Monkey Model
Our unanesthetized monkey preparation presents several
advantages for the study of focal cerebral ischemia. This
primate species simulates closely the human cerebrovascular system, and the snare ligature technique eliminates the
confusing effects of general anesthesia.4"5 This snare ligature
method uniquely permits precisely reproducible temporary
MCA occlusion. 56 Ischemia-modifying factors' can be
readily monitored in this preparation, and neurologic examinations can be performed.
The most notable deviations from normal in these animals
were the hypertension and hypocapneic alkalosis induced by
variable hyperventilation. In this sense, the unanesthetized
state is itself a variable for such cerebrovascular studies. It
may be possible to limit agitation by conditioning monkeys
to the restraining chair and strictly limiting sensory stimulation. Another deviation from normal was the declining
hematocrit, probably resulting from repeated blood gas
sampling. Monitoring of end-tidal CO 2 and placement of intraarterial oxygen electrodes may decrease need for blood
sampling and thus eliminate the fall in hematocrit.
Local Cerebral Blood Flow
The values of ICBF recorded here in basal ganglia are less
than those reported by others.8'12> 16 This is likely related to
chronic hyperventilation in these awake monkeys and to the
large size of our electrodes (2mm exposed tip). Some of the
variation in ICBF recorded from a single electrode may be
related to changes in alertness. The monoexponential character of most wash-out curves suggests a restricted locus of
STROKE
148
VOL 9, No
2, MARCH-APRIL
1978
Electrode
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PREOCCLUSION
OCCLUSION
(123min.)
POST-OCCLUSION
POSTOCCLUSION
OCCLUSION
(126min.)
FIGURE 3. Poor collateral supply — massive fatal infarction. Left: (Monkey §5): Marked hemiparesis
during 2 hour profound ischemia. Fatal course with marked hyperemia after deocclusion: massive hemorrhagic infarction. Right: (Monkey §4): Marked hemiparesis during 2 hour profound ischemia. Fatal course
with delayed marked hyperemia after deocclusion; massive infarction. Note that only monkeys §4 and §5
had subarachnoid hemorrhage during ligature placement.
501-
40
o
o
5
\
§
Response to MCA Occlusion
30
\
20
5!
blood flow monitoring. That the electrodes indeed determine flow in largely uninjured tissue is suggested by the
relative stability of 1CBF values over time, the preservation
of autoregulation and C0 2 responsivity and the limited
histological reaction.
8
10 -
120
150
180
PERM.
TIME, min.
FIGURE 4. Infarction threshold. Pooled data from 6 monkeys.
Open circles stand for electrodes lying in preserved tissue, black
squares are electrodes lying in infarcted tissue, and half-black
squares are electrodes on the edge of infarction. Note the infarction
threshold at about
I2cc/IOOgm/min.
As in the cat,5 MCA occlusion caused immediate deficit
and ischemia. Residual 1CBF generally stayed constant during 2-3 hour MCA occlusion; that is, early failure or
enhancement of collateral was not seen.1 Diaschisis was not
observed; in fact, most animals showed contralateral
hyperemia during occlusion.
Slight subarachnoid hemorrhage during preparatory surgery occurred in 2 animals and was associated in both with
profound ischemia and infarction. Vasospasm, though
asymptomatic before occlusion, may well have compromised the collateral supply in these animals. We suspect
that massive infarction may have been a byproduct of unwanted surgical subarachnoid bleeding, not of a pre-existing
paucity of collateral supply.
Response to De-occlusion
Since MCA de-occlusion always led to normal or
hyperemic 1CBF, no evidence for impaired reperfusion2 was
CBF DURING MCA OCCLUSION/A/orawfz et al.
FIGURE 5.
149
Horizontal
sections
of
brain.
Loyez stain for myelin. A. Experiment §3. Infarcled tissue is outlined by thick arrow heads.
Electrode tracts seen as holes are numbered
1-6. Electrodes I and 2 are within the infarcted zone, electrode 3 borders the infarct.
and electrode 6 is the control electrode in the
putamen contralateral to the occluded middle
cerebral artery. B. (Inset) Experiment §2.
Electrode tracts 1-5 in non-infarcted tissue.
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observed in these experiments. In 3 animals with moderate
ischemia, restoration of flow led to improved 1CBF and
neurologic status, but in 2 monkeys with profound ischemia,
restoration offlowwas probably deleterious (cerebral edema
and hemorrhagic infarction,fig.3).3 Marked reactive hyperemia heralded infarction, but in 1 case moderate reactive
hyperemia was associated with full recovery.
Physiologic-Pathologic Correlations
The close correlation of residual 1CBF from collateral
with infarct size supports the concept that variability in
strokes is related to variable collateral supply.1' '• "
In these experiments, infarction occurred in unanesthetized monkey brain after MCA occlusion if 1CBF fell
below 12cc/100g/min for 120 to 180 minutes. This infarction threshold corresponds roughly to the level of about
lOcc/lOOg/min below which substantial release of K + occurs in the brain.18 Ischemic injury probably is related to the
time of exposure to a level of ischemia and the duration of
exposure to that level of ischemia. Therefore, infarction requires lower flow values if exposure time is short. Further
experiments will be needed to establish this point.
Conceivably, such an infarction threshold could be used to
diagnose irreversible damage and aid selection of cases for
surgical revascularization. A threshold for temporary functioned derangement is likely significantly higher. When
CBF falls below 17-18cc/100g/min in anesthetized humans,
major abnormalities appear.19
Acknowledgment
We thank Drs. Adelbert Ames, Richard Masland, Thomas Jones, and
Jonathan Shay for helpful comments, Mrs. Edith Tagrin for the illustrations,
and Ms Mary Pat Kingsbury and Ms. Kay Hynds for typing the manuscript.
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R B Morawetz, U DeGirolami, R G Ojemann, F W Marcoux and R M Crowell
Stroke. 1978;9:143-149
doi: 10.1161/01.STR.9.2.143
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