442

Hypotension As A Complication Of Hypoglycemia

Leads To Enhanced Energy Failure But No
Increase In Neuronal Necrosis
ROLAND N. A U E R , M . D . ,

P H . D . , PER H A L L , M . D . ,
AND B o K. SIESJO, M . D . ,

MARTIN INGVAR, M . D . ,

PH.D.,

PH.D.

SUMMARY The hypothesis that arterial hypotension aggravates hypoglycemic brain damage was tested.
Thirty minutes of insulin induced hypoglycemia with a flat EEG ("isoelectricity") was compared in seven
series of rats. In three series of animals, the energy state of the cerebral cortex was determined at blood
pressures of 140, 100 and 80 nun Hg respectively. Hypotension during hypoglycemia exacerbated cortical
energy failure. In the fourth to sixth series, blood pressure was adjusted during isoelectricity to 160,100 and
60 mm Hg, respectively. A seventh series had induced hypotension to 60 mm Hg only in the recovery period.
Quantitation of neuronal death was performed in the fourth to seventh series of rats by direct visual
counting of acidophilic neurons in sub-serially sectioned brains after one week survival. Although the first
three series demonstrated enhanced deterioration of the cerebral energy state with lower blood pressures
during hypoglycemia, the fourth to seventh series showed no augmentation of quantitated hypoglycemic
neuronal necrosis. The distinct distribution of hypoglycemic brain damage, suggesting a fluid-borne toxin,
was present at normal and reduced blood pressures, with no tendency toward an ischemic pattern of
pathology. In spite of previously demonstrated reductions of cerebral blood flow to Ischemic levels In regions
with pronounced loss of autoregulation, no regional exacerbation of neuronal necrosis was seen in these
brain areas. It is concluded that hypoglycemic brain damage is distinct from ischemic brain damage, and
that the two insults are not additive. Furthermore, moderate hypotension to 60 mm Hg does not aggravate
the damage in spite of an enhanced energy failure.
Stroke Vol 17, No 3, 1986

CONSIDERABLE INFORMATION NOW EXISTS

on the neurochemical effects of severe insulin-induced
hypoglycemia, as well as on the brain damage which
may be incurred as a result of the hypoglycemia. Observations in man, and in animal experiments, demonstrate that stupor and coma, or their EEG equivalents,
are accompanied by a reduced cerebral glucose utilization, at an unchanged or only slightly reduced oxygen
consumption.1"6 Subsequent experimental studies gave
detailed information on endogenous substrates utilized
by the glucose-deprived (for literature, see Siesjo and
Agardh). 7 These studies also showed that cessation of
spontaneous EEG activity ("isoelectricity") occurs
pari passu with deterioration of cerebral energy state,
eg. with reduction in phosphocreatine (PCr) and ATP
concentrations, and corresponding increases in ADP
and AMP concentrations.8"" The energy failure also
leads to loss of ion homeostasis, since massive cellular
efflux of K + l0 and uptake of Ca + 12'13 are observed.
Several observations suggest that hypoglycemia
does not normally encroach upon cellular oxygen supply. Thus, studies designed to provide information on
oxygen and glucose utilization (see above) showed that
cerebral blood flow (CBF) is well maintained. Subsequent autoradiographic CBF measurements corroboFrom the Laboratory for Experimental Brain Research, University
Hospital, S-221 85 Lund, Sweden.
Supported by grants from the Swedish Medical Research Council
(I2X-03020) and the National Institutes of Health of the United States
Public Health Service (5 R01 NSO7838).
Dr. Roland N. Auer is the recipient of a Medical Research Council of
Canada Fellowship.
Address correspondence to: Roland N. Auer, M.D., Health Sciences
Centre, University of Calgary, 3330 Hospital Drive N.W., Calgary,
Alberta, Canada T2N 1N4.
Received April 19, 1985; revision # 1 accepted November 1, 1985.

rated these observations. 1415 In fact, these studies

showed that if blood pressure is maintained at values
of 140-160 mm Hg, CBF is generally increased, in
many structures to 200-300% of control.14'15 Furthermore, analysis of neurochemical variables suggest that
cellular redox systems are oxidized during hypoglycemia.4- l6
All these studies allowed tight control of physiological variables such as blood pressure and arterial oxygenation. This has neither been the case in clinical
material which has documented neuronal necrosis as a
result of hypoglycemia,17"21 nor in earlier experimental
studies confirming the clinical observations.22"24 Indeed, hypotension and/or hypoxia as contributing
causes seemed likely. Thus, hypoglycemic and ischemic brain damage were considered identical,25"29 and
hypotension was assumed to exacerbate hypoglycemic
brain damage. 28 ' M Hypoglycemia was thought to be a
form of hypoxia. 26 ' 2729
The advent of a physiologically controlled animal
model which allows the delivery of purely hypoglycemic insults, followed by long term survival, has
brought new information on the density and distribution of hypoglycemic neuronal necrosis. 3031 It has
been shown that neuronal necrosis does not occur unless the EEG becomes isoelectric,30 suggesting that
energy failure and loss of ion homeostasis are prerequisites for damage to be incurred. Furthermore, a
comparison between hypoglycemic and ischemic insults in the same species demonstrates that the distribution of neuronal necrosis is not identical in the two
conditions. 3132
Although these results demonstrate that hypoglycemic brain damage can be incurred in the absence of
cellular hypoxia, they do not provide an answer to the

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HYPOTENSION AND HYPOGLYCEMIAMuer et al

important question of whether arterial hypotension

will aggravate hypoglycemic brain damage. Some recent results provide hints that this could be the case.
Thus, experiments on cerebral acid-base regulation in
severe hypocapnia (PaCO2 15 mm Hg) showed that
moderate hypotension further aggravated the deterioration of cerebral energy state, caused by hypoglycemia.33 Finally, it could be shown that vascular autoregulation was lost during hypoglycemia, and that even
relatively moderatereductionsin blood pressure could
severely reduce local CBF.13
With this background, we wished to test the hypothesis that hypoglycemic brain damage, defined as
neuronal necrosis, is exacerbated by hypotension.
Seven groups of animals were studied. In three, the
influence of hypotension during hypoglycemia on the
cortical energy state was investigated. To that end,
blood pressure was held at 160, 100, and 80 mm Hg in
three separate groups, during a 30 min period of
isoelectricity, and labile phosphates were analyzed in
neocortical tissue. In four groups, rats were subjected
to a standard hypoglycemic insult at varying blood
pressures, and were then allowed to recover one week
before perfusion fixation, followed by quantitative histopathological examination.
Materials and Methods
Seventy six male Wistar rats weighing 290-345 g
were used (M0llegaard Breeding Center, Copenhagen). The animals for the metabolite series were divided into groups with high (group A, about 140 mm Hg),

443

medium (group B, 100 mm Hg), and low (group C, 80

mm Hg) blood pressures (table 1). At each pressure,
brains were frozen in situ for metabolite measurements
after 5 and after 30 min isoelectricity. Normoglycemic
control brains were similarly analyzed at 140-160 mm
Hg and 100 mm Hg.
The animals for the histopathology series were also
divided into high (D), medium (E), and low pressure
(F) groups (table 1). However, to ensure that the high
pressure group had high cerebral perfusion rates, the
animals were regulated to a pressure of at least 140
mm Hg. Furthermore, to ensure that the low pressure
animals had enhanced deterioration of cerebral energy
state, they were kept at a blood pressure of 60 mm Hg
during the period of isoelectricity.
A seventh series (G) was also examined by quantitative histopathology. Here the blood pressure was held
at 140 to 160 mm Hg during the isoelectric period, but
was lowered to 60 mm Hg in the recovery period.
A previous publication describes more completely
the model used.30 Briefly, the rats were fasted overnight with free access to tap water. The next day, they
were given 9-21 I.U./kg of regular insulin (Actrapid,
Novo Industri A/S, Copenhagen), immersed in 3%
halothane, intubated, and mechanically ventilated with
0.8% halothane in a 2:1 N2O:O2 mixture. Two tail
veins, and the tail artery were then cannulated, and
continuous paralysis maintained via an i.v. infusion of
suxamethonium. A bipolar interhemispheric electroencephalogram (EEG) was continuously monitored.
The halothane was discontinued, the animals were

TABLE 1 Physiologic Parameters During Hypoglycemia

Blood
No. of
PO2
PCO2
MABP
glucose
Temp
animals (mm Hg)
Group
(mm Hg)
(mM)
(mm Hg)
pH
CO
8
7.35 0.05
103ll
1369
37.0 + 0.6
Control 1*
35.41.2
7.390.04
968
978
37.20.5
Control 2*
32.91.5
6
37.0 + 0.2
A 5'
7.340.04
6
143+6
1009
32.01.6
7.340.04
142 4
6
101 7
34.5 + 3.0
37.0 + 0.3
A 30'
7.360.17
B 5'
101 2
36.8 0.4
10810
30.510.4
6
4
B 30'
37.0 + 0.3
32.92.1
7.31 0.07
101 6
110 + 20
37.1 4.4
7.290.O9
6
800
1069
C5'
36.9 + 0.3
7.29O.O3
8
C30'
792
105 5
37.0 + 0.3
32.02.7
7.38 + 0.05
15912
D
93 + 24
37.3+0.3
37.24
0.530.17
6
7.37 0.05
0.41 0.15
8
37.3 + 0.2
35.72
105 10
1042
E
7.41 0.06
37.30.2
33.8 + 3
F
0.350.09
6
602
946
37.5 + 0.4
37.44
7.380.06
0.310.12
6
G
1099
636t
The values are taken at the end of the given EEG isoelectric period.
All values are given as mean standard deviation.
Control 1 denotes a normoglycemic group with spontaneous blood pressure of 140 to 160 mm Hg. Control 2 denotes a
normoglycemic group exsanguinated to a blood pressure of 100 mm Hg.
Group A: High BP, metabolite analysis.
Group B: Medium BP, metabolite analysis.
Group C: Low BP, metabolite analysis.
Group D: High BP, histologic analysis.
Group E: Medium BP, histologic analysis.
Group F: Low BP, histologic analysis.
Group G: Low BP in recovery only, histologic analysis.
Mean arterial blood pressure in the first 30 min of recovery.

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STROKE

444

160
140
a
E 1 20
E

100
3

80

13

o
m

eo
40
20 -

15

10
Hlnutai

of

20

25

30

l>o*lctrlclty

FIOURE 1. Blood pressure as a function of duration of isoelectricity for each group. All values are standard deviation.

ventilated on a 2:1 N2O:O2 mixture, and a flat EEG

("isoelectricity") was awaited.
During isoelectricity, blood pressure was held at the
desired level through controlled exsanguination and
re-infusion of blood. The actual blood pressures
throughout the period of isoelectricity are given in
figure 1 for the histopathology series D to F. The
temperature, arterial PO2, PC0 2 , and pH were maintained within the physiological range.
The animals in which the energy metabolites were
studied had a funnel fitted onto the skull. The brain
was then frozen in situ according to Ponte"n et al.34
After removal of the brain from the skull it was kept at
80C until analyzed. Fragments weighing approximately 25 mg were dissected from the parietal cortex at
20C, and were extracted in HCl-methanol and subsequently in perchloric acid at 0C. After neutralization, the metabolites were determined fluorometrically.35 The conditions for the anlayses have been
previously described.3637
After thirty minutes of EEG isoelectricity the animals in the histopathology series were recovered with
an infusion of 0.2 ml of 50% glucose, given by hand
over one minute. A 50% glucose infusion was then
tapered over the ensuing hours, and substituted with
25% glucose in Krebs-Henseleit solution overnight, in
order to maintain a plasma glucose of between 5 and 10
mM/1. Following extubation, usually one to three
hours after glucose induced recovery, blood glucose,
blood gases and pH were checked finally in the awake,
conscious animal before removal of the tail catheters.
The animals were weighed and examined daily, and

3, MAY-JUNE

1986

were allowed to survive one week. They were sacrificed by perfusion fixation with 4% phosphate buffered formaldehyde under 1% halothane anesthesia.
The brains were left in situ at 4C and were removed
the following day. After processing in graded ethanols
and xylol, they were embedded in paraffin and subserially sectioned at 8 fim.
Sections were double stained with acid fuchsin and
cresyl violet, and the number of acidophilic neurons
was assessed by direct visual counting of sections at
standardized control levels of the brain.30
The crude damage index (CDI) was generated as
follows: For the caudate nucleus, subiculum, CA1 pyramidal neurons, and dentate granule neurons, the following numbers were assigned for the per cent neuronal necrosis: <10% = 1, 10-50% = 2, and
50-100% = 3. For the cerebral cortex, 10 to 100
necrotic neurons per section was assigned the number
1,100 to 1000 the number 2, and > 1000 the number 3.
These integers were added to produce the CDI for each
brain.

100

VOL 17, No

Results
Physiologic parameters during EEG isoelectricity
are shown in table 1. All animals were normothermic
and normoxic, and their PCO2 and pH values showed
little deviation from control. Results from the metabolite series demonstrate that mean arterial blood pressure was kept constant between the 5th and the 30th
minute. Corresponding blood pressure data from the
histology series are shown in figure 1. The blood pressure in the recovery period in the post-insult hypotension group was comparable to that shown during isoelectricity in the low blood pressure group, i.e. roughly
60 mm Hg.
1. Cerebral Metabolites
Cerebral metabolic changes were similar after 5 and
30 min of isoelectricity, demonstrating that a new
steady state is reached soon after cessation of EEG
activity."138 Due to this constancy, we will discuss the
30 min data only. Furthermore, since the hypotensive
control animals had values identical to normotensive
ones, only the latter are shown in table 2, which gives
tissue metabolites. In all isoelectric animals, tissue
glucose concentrations were very low. In the normotensive group, PCr and ATP concentrations decreased
to about 10% and about 25% of control, respectively,
with corresponding increases in ADP and AMP concentrations. As expected, lactate and pyruvate concentrations were reduced.

TABLE 2 Cerebral Cortical Concentrations of Labile Energy Metabolites During Insulin Induced Hypogtycemia in Animals Subjected to
Different Blood Pressures During the Hypoglycemic Period
Group
Control
A(BP140)
B(BP100)
C(BP80)

Glucose

PCr

ATP

2.25 + 0.39
0.07+0.03
0.140.11
0.03 + 0.01

4.460.18
0.570.11
0.5O0.08
0.22 + 0.05

2.830.04
0.81 0.11
0.720.14
0.360.05

ADP

O.275O.O08
0.9150.091
0.821 0.075
0.7240.028
The values are given in ^imol g ' wet weight and represent means

AMP

Energy
charge

0.0660.012 0.9370.003
0.4470.025 0.5800.026
O.575O.O56 0.5320.027
0.7680.027 0.3700.021
standard error of the mean.

Lactate

Pyruvate

1.51 0.11
0.41 0.09
O.380.O8
0.330.04

0.1080.007
0.0360.OO2
O.O19O.OO5
0.0220.002

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44S

HYPOTENSION AND HYPOGLYCEMIAMiarr et al

Hg, 0.53 at 100 mm Hg, and sank to 0.37 at 80 mm

Hg. In order to illustrate the pressure-dependent deterioration of cerebral energy state, individual values for
ATP and energy charge were plotted against blood
pressure (fig. 2). The results demonstrate a significant
correlation (p < 0.01). At a blood pressure of 80 mm
Hg, PCr and ATP concentrations were reduced to 5
and 10% of control respectively.

1.50 r-

o> 1.00

a.
L

<

0.60

0.00

eo

ao

100

120

100

0.7
0.6
O.S

. 0.4
U
" 0.3
r 0.77
p 0.0 1

0.2
0.1
0.0 eo

80

100
120
140
Blood p t i i i g n tnmHg

180

FIGURE 2. Tissue level of ATP and energy change as a function of blood pressure in animals subjected to 30 min ofhypoglycemia with an isoelectric EEC

The results of table 2 demonstrate that hypotension

further reduced PCr and ATP concentrations, as well
as the calculated adenylate energy charge, as defined
by Atkinson.39 The cortical energy charge during hypoglycemia was 0.58 at a blood pressure of 140 mm

2. Hlstopathotogy
The density of neuronal necrosis was determined by
direct visual cell counts in each of the major brain
regions. The data are summarized in table 3.* As the
results demonstrate, no effect of hypotension in enhancing neuronal necrosis was seen. The results obtained in the group maintained hypotensive for 30
min in the immediate recovery period were likewise
negative.
Figure 3 plots the crude damage index, derived from
the number of necrotic neurons in each brain region
(see Material and Methods) against the blood pressure.
It is apparent that there was considerable variation in
brain damage within each group, but the degree of
damage was unchanged by lowering the blood pressure
to either 100 mm Hg or 60 mm Hg.
Not only the density of brain damage, but also the
distribution of hypoglycemic brain damage was unaltered by lowering the blood pressure to 100 or to 60
mm Hg. Affected areas included the dentate gyrus (fig.
4), the cerebral cortex (fig. 5) and septal nuclei (fig. 6)
in a pattern identical to that seen after hypoglycemia at
a blood pressure of 160 mm Hg. Thus, the crest and the
external blade of the dentate gyrus were affected first.
The superficial cerebral cortical layers showed the
most damage, with a superficial to deep gradient seen.
The cerebellum was affected near the foramena of
Luschka, with numerous necrotic Purkinje cells seen

to
9

CA1

o a
o
s
4
3

1
60
SO
100 120 140
Blood pr*tsar mm Hg

FIGURE 3. Crude damage index as a function of mean BP

during 30 min isoelectricity. Neither lowering the BP to 100,
nor to 60 had an effect on the quantitated brain damage.

FIGURE 4. Histologic appearance of hippocampal damage,

one week after 30 min of hypoglycemic isoelectricity complicated by hypotension to 60 mm Hg. The distribution is identical to
that seen after hypoglycemic isoelectricity accompanied by a
BP of 100 or 160. There is neuronal necrosis at the crest and
external blade of the dentate gyrus (D), and in the CA1 pyramidal cells (CA1), especially medially near the subiculum (S).
Acid fuchsinlCresyl violet. Bar = 200 fun.

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446

STROKE

VOL

17, No

3, MAY-JUNE

1986

SEPTAL NUCLEI

I
\,

FIOURE 5. The cingulate gyri (CING), structures showing

marked loss of autoregulation, and a consequent drop in blood
flow to ischemic levels during hypogfycemia accompanied by
hypotension to 60 mm Hg, nevertheless show relative sparing
compared to the neuronal necrosis seen in the surrounding
superficial cortex (arrows). Acid fuchsinlCresyl violet. Bar =
250 tun.

over the hemispheres in some animals (not shown).

Infarction was never seen.
No features regarding the distribution of neuronal
necrosis serve to distinguish the brain damage observed in the present study from that previously reported in normotensive hypoglycemia.31 However, due to
the marked regional differences in the degree of remaining autoregulation, special attention was focussed
on certain brain regions histologically. The cingulate
gyrus is known to have an ischemic flow rate during
hypotensive hypoglycemia as studied here,15 and increased neuronal necrosis might therefore be expected
in this region. However, the cingulate gyrus showed
sparing, rather than enhancement of neuronal necrosis
(fig. 5), a distribution pattern also seen in hypoglycemia at normal blood pressure levels.31
In contrast to the cingulate gyri, the septal nuclei
show relative preservation of autoregulation, and
hence blood flow, in the range of blood pressures tested.15 They might therefore be expected to show sparing, if blood flow factors are operant in causing neuronal necrosis in hypoglycemia. Nevertheless, the
septal nuclei demonstrated selective neuronal necrosis
histologically (fig. 6).
Discussion
Hypotension has long been assumed to exacerbate
hypoglycemic brain damage.28'N The present experiTABLE 3 Summary of Histologic Data*
Dentate
Caudate
Group
%
%
D (BP 160)
796
143
837
E (BP 100)
195
154
F (BP 60)
806
787
G (BP 60 in recovery)
126
All values mean standard error of the mean.
No statistically significant differences were noted

FIGURE 6. The septal nuclei, a brain region showing relative

preservation of autoregulation during hypoglycemia, consequentty undergoing only minor decreases in blood flow secondary to hypotension, nevertheless show neuronal necrosis (arrows). Acid fuchsinlCresyl violet. Bar = 500 fjun.

ments were designed to test this hypothesis, and are

based on an animal model which allows tight control of
physiologic parameters, as well as long term survival.
The former was considered necessary to unequivocally
dissect out cause and effect relationships between the
physiologic and metabolic data during and after the
insult, and the consequent neuronal damage. The latter
was deemed necessary to allow for the unequivocal
signs of neuronal necrosis to develop.
The results demonstrate a very marked dichotomy
and are somewhat surprising. The metabolic part of
this study showed enhanced deterioration of the cereCA1
%

178
117
266
21 + 13

Subiculum
%
777
885
933
829

Tabulated data from each animal may be found in the Appendix.

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Cortex,
cells
145 78
11537
201 85
10971

447

HYPOTENSION AND HYPOGLYCEMIAMuer et al

bral energy state when low blood pressure accompanied hypoglycemia. However, there was no effect of
hypotension to 60 mm Hg, either during or after the
period of isoelectric EEG, on either the density or the
distribution of hypoglycemic neuronal necrosis.
As stated in the introduction, results obtained in
severely hypocapnic animals demonstrated a relationship between blood pressure and the adenylate energy
charge of neocortical tissue, suggesting that even moderate hypotension will aggravate the deterioration of
cellular energy metabolism during hypoglycemia.40
Results obtained with measurements of extracellular
K + activity were in line with this conclusion.33 These
results, and those showing regional loss of vascular
autoregulation in many brain structures during hypoglycemia,15 suggest that hypotension during hypoglycemia leads to a reduction in flow rate from hyperemic14- " levels which are of sufficient magnitude to
further reduce glucose delivery to the substrate-deprived cells. The present results indicate that these
events do not increase neuronal necrosis.
It is of considerable interest that a reduction of ATP
concentration to 0.36 0.05 mol-g~' of tissue, as
occurred in the group C, did not aggravate hypoglycemic neuronal necrosis. In fact, since the histopathology group F had an even lower blood pressure (60 mm
Hg) than the metabolite group C (80 mm Hg), it would
seem that a more severe reduction of ATP concentration causes no aggravation of the neuronal death. The
results suggest that the events which lead to hypoglycemic neuronal necrosis occur already at a normal or
reduced blood pressure, and are not dependent on
blood flow. Such events include a reduction of ATP
concentration to about 25% of control, marked increases in ammonia concentrations,1 aspartate41 and in
free fatty acid concentrations,42 massive depolarization
of cells with release of K + , 10 ' 33 and reductions of extracellular Ca 2+ concentration to very low levels, probably because of influx into cells.12-13
It now seems established that hypoglycemia leads to
neuronal necrosis with a different distribution in the rat
from that observed in ischemia.30"32 The ischemic pattern of distribution shows involvement of the middle
cortical layers, uniform involvement of the CA1 pyramidal cell band of the hippocampus, but conspicuous
sparing of the dentate gyms until damage is very
severe.32
The hypoglycemic pattern of distribution involves
an affectation of the superficial layers" of neocortical
cells, medial CA1 pyramidal cells of the hippocampus,
and heavy affectation of cells at the crest of the dentate
gyms, the conspicuous relationship of neuronal necrosis to tissue fluid and CSF pathways suggesting the
participation of a fluid-borne toxin.31 Dark neurons are
seen acutely, and acidophilic neurons subsequently, in
all these brain regions.43^5 Although the dark neurons
may potentially recover,43 the acidophilic neurons are
established as necrotic by their mitochondrial flocculent densities and absent cell membranes, and by their
subsequent removal from the tissue.43-t5 It is this acidophilic neuronal necrosis which was quantitated at one

week survival in the present study, rather than acute,

potentially reversible neuronal changes.43
Since the distribution of neuronal necrosis is not the
same in ischemia and hypoglycemia, it is possible to
distinguish hypoglycemic31 and ischemic32 patterns of
brain damage. Lowering the blood pressure during,
and after the period of hypoglycemic isoelectricity
might theoretically have given rise to an ischemic pattern of brain damage, a hypoglycemic pattern of brain
damage, or even a combination of the two. It is of
interest that hypotension did not alter the pattern of
distribution of neuronal necrosis from one typical of
hypoglycemia to one more characteristic of ischemia.
Since the density of hypoglycemic brain damage was
also unaffected by hypotension, one may conclude that
formation of the hypothetical toxin is not enhanced
when ATP concentrations are further reduced.
Infarction was not seen in the present study. Pannecrosis of all cell types of the CNS, comprising brain
infarction, has been linked to lactic acid production.46"50 In hypoglycemia, lactic acid formation is impossible due to glucose deficiency. Since the addition
of hypotension to hypoglycemia actually caused ischemic blood flow rates in areas such as the cingulate
cortex,15 and since such areas were relatively spared of
damage, the present results may be construed as demonstrating that profound hypoglycemia actually protects against infarction.
Acknowledgments
The authors appreciate the technical assistance of Helene Wilhelmsson, Karin Hansson, Kerstin Beirup, Lille-Mor Lindestrdm, Marianne
Forssen, and Maud Salomonsson, and the secretarial skill of Donna
Wilson in typing the manuscript.

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HYPOTENSION AND HYPOGLYCEMIAMwrr et al

449

Appendix
Hypotension and Hypoglycemia
Data available on request
Glucose
30-iso
8809
0.62 mM 15 min
BP 153
12 I.U./kg
0.61 mM 28 min
30-iso
8835
0.76 mM 15 min
BP 177
17 I.U./kg
0.81 mM 28 min
30-iso
8847
0.49 mM 15 min
BP 159
16 I.U./kg
0.43 mM 28 min
8855
0.72 mM 15 min
30-iso
BP 152
21 I.U./kg
0.47 mM 27 min
30-iso
8872
0.58 mM 15 mm
BP 167
15 I.U./kg
0.18 mM 28 min
30-iso
8959
0.35 mM 15 min
BP 144
9 I.U./kg
0.30 mM 28 min
30-iso
8807
0.53 mM 15 min
BP 102
13 I.U./kg
0.25 mM 28 min
30-iso
8821
0.73 mM 15 min
BP 107
11 I.U./kg
30-iso
8979
0.52 mM 15 min
BP 105
11 I.U./kg
0.40 mM 25 min
30-iso
8980
0.56 mM 15 min
BP 103
11 I.U./kg
0.21 mM 27 min
30-iso
8983
0.35 mM 15 min
28 min
BP 105
12 I.U./kg
0.36
30-iso
8986
0.18 mM 15 min
BP 103
11 I.U./kg
0.22 mM 28 min
30-iso
8987
0.46 mM 15 min
BP 103
11 I.U./kg
0.31 mM 28 min
30-iso
8989
0.50 mM 15 min
BP 102
12 I.U./kg
0.29 mM 27 min
30-iso
8911
0.53 mM 15 min
BP56
10 I.U./kg
0.42 mM 25 min
30-iso
8982
0.45 mM 15 min
BP63
11 I.U./kg
0.30 mM 25 min
30-iso
8984
0.29 mM 15 min
BP59
11 I.U./kg
0.14 mM 28 min
30-iso
8985
0.32 mM 15 min
BP59
12 I.U./kg
0.28 mM 28 min
30-iso
8988
0.47 mM 15 min
BP61
0.30 mM 28 min
10 I.U./kg
30-iso
12030
0.32 mM 15 min
BP61
12 I.U./kg
0.36 mM 28 min
30-BP 50 12043
0.88 mM 0 min
in Rec
6 I.U./kg
0.34 mM 26 min
30-BP 60 12047
0.60 mM 0 min
in Rec
5 I.U./kg
0.40 mM 26 min
30-BP 60 12048
0.75 mM 0 min
in Rec
0.50 mM 26 min
5 I.U./kg
30-BP 60 12049
0.68 mM 0 min
in Rec
5 I.U./kg
0.19 mM 26 min
30-BP 80 12053
0.80 mM 0 min
in Rec
5 I.U./kg
0.20 mM 20 min
30-BP 80 12054
1.1 mM 0 min
in Rec
5 I.U./kg
0.25 mM 25 min

Caud
iso
iso
ISO

iso
iso
iso
ISO

iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
ISO

iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
ISO

iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
iso
ISO

iso
iso
iso

85%
94%
55%
91%
67%
97%
94%
80%
70%
79%
68%
66%
87%
86%
48%
90%
89%
96%
91%
90%
90%
88%
98%
99%
43%
45%
95%
98%
78%
68%
90%
71%

63%
56%
98%
90%
98%
97%
74%
77%

90%
61%
91%
99%
62%
69%
86%
78%
95%
86%
44%
71%

Dent
2.8%
3.5%
16%
19%
14%
28%
13%
15%
23%
24%
6%
6%
29%
30%
8.2%
8.2%
12%
10%
8%
9%
19%
19%
22%
15%
4%
3%
49%
54%
13%
2%

9%
9%
12%
15%
32%
31%
9%
7%
13%
24%
1.8%
2.3%
1.5%
2.6%
4%
4%
19%
12%
41%
42%
5%
7%

CA1

Sub

II-III

IV-VI

0.85%
0.55%

47%
36%
88%
86%

cells
cells
cells
cells
cells
cells
cells
cells
cells
cells
6 cells
10 cells
120 cells
95 cells
58 cells
51 cells
24 cells
16 cells
76 cells
129 cells
7 cells
9 cells
294 cells
186 cells
58 cells
104 cells
284 cells
341 cells
70 cells
19 cells
141 cells
188 cells
85 cells
204 cells
312 cells
286 cells
740 cells
364 cells
2 cells
1 cells
45 cells
65 cells
23 cells
42 cells
12 cells
18 cells
16 cells
44 cells
420 cells
535 cells
25 cells
67 cells

0 cells
0 cells
9 cells
9 cells
0 cells
0 cells
4 cells
3 cells
3 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
2 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
22 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells
0 cells

58%
49%
21%
37%
10%

2.3%
14%
13%

1.8%
2.3%
24%
12%

1.4%
1.3%
0.35%
5%

0.65%
0.51%
0.74%
0.7%
4%
5%

0.16%
0.09%
62%
54%
8%
22%
27%
22%
35%
37%
34%
37%
37%
50%

0.3%
7%
0%

.07%
81%
81%
3%
12%
0%

0%
36%
30%
2.6%
3.2%

81%
94%
94%
78%
82%
94%
71%
76%
90%
79%
85%
89%
90%
90%
98%
98%
99%
99%
95%

99%
60%
50%
98%
98%
91%
89%
90%
97%
70%
94%
99%
99%
95%

100%
95%

100%
44%
45%

100%
100%
72%
95%

53%
76%
100%
100%
100%
95%

108
70
624
238
14
423
107
21
70
50

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Hypotension as a complication of hypoglycemia leads to enhanced energy failure but no

increase in neuronal necrosis.
R N Auer, P Hall, M Ingvar and B K Siesjo
Stroke. 1986;17:442-449
doi: 10.1161/01.STR.17.3.442
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 1986 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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