108
STROKE
tension caused by bleeding. Acta Physiol Scand 87: 1-14, 1973
37. Hamar J, Kovach AGB, Reivich M, Nyary I, Durity F: Effect of
phenoxybenzamine on cerebral blood flow and metabolism in the
baboon during hemorrhagic shock. Stroke 10: 401-407, 1979
38. Ruff RL, Talman WT, Petito F: Transient ischemic attacks associated with hypotension in hypertensive patients with carotid artery
stenosis Stroke 12: 353-355, 1981
39. Hulse JA, Taylor DSI, Dillon MJ: Blindness and paraplegia in
VOL
15,
No
1, JANUARY-FEBRUARY
1984
severe childhood hypertension. Lancet 2: 553-556, 1979
40. Britton M, deFaire U, Helmers C: Hazards of therapy for excessive
hypertension in acute stroke. Acta Med Scand 207: 253-257, 1980
41. Auer LM, Sayama I, Johansson BB: Cerebrovascular effects of
dihydralazine in hypertensive and normotensive rats. In Strandgaard S, Barry DI (Eds) Cerebral blood flow, Hypertension and
antihypertensive treatment. Acta Med Scand Suppl. 678, p73—81,
1983
Local Vascular Response to Change in Carbon
Dioxide Tension. Long Term Observation in
the Cat's Brain by Means of the Hydrogen
Clearance Technique
Downloaded from http://stroke.ahajournals.org/ by guest on July 31, 2017
RlJDIGER V. KUMMER, M . D .
SUMMARY Thirty six small hydrogen sensitive electrodes were inserted into the brains of 6 cats to
evaluate the local vascular response to change in PaCO 2 , of cortex, subcortical white matter, and caudate
nucleus. Repeated measurements (617) of local cerebral blood flow (ICBF) were performed over a period of
12 weeks. Within a PaCO 2 range from 19 to 96 mmHg the local response of CBF was linear in most of the
regions measured. The absolute local CO 2 reactivity (CO2-R) showed a positive correlation to ICBF at
PaCO 2 = 40 mmHg (ICBF40) with the regression line: absolute CO2-R = 0.02 ICBF^ + 0.22, r = 0.71 (p
< 0.01). Therefore relative ICBF change was calculated in relation to ICBF40 to make comparisons between
the CO 2 response of different measuring days and of different regions examined. No significant change in
relative CO 2 -R was observed during the 12 weeks interval. Differences of relative CO2-R between investigated regions were insignificant. The uniformity of relative CO 2 response might support the hypothesis of a
direct effect of PaCO 2 or pH on the vessel wall. For comparison of CBF, the individual determination of
CBF40 and relative CO 2 -R would be necessary.
Stroke Vol 15, No I, 1984
ALTHOUGH ARTERIAL carbon dioxide tension
(PaCO2) has often been confirmed as a prominent factor of circulatory control in the central nervous system
(CNS) since regional CBF measurements were performed,1"12 the quantitative relationship between local
cerebral blood flow (ICBF) and PaCO2 is not yet clear.
Within physiologic ranges of PaCO2, the vascular response has been described to be linear2"5 l0 " but also
as an exponential function.' 8 9 n This has led to uncertainty in calculations of CBF when adjustments for
changes in PaCO2 are necessary. It is also uncertain
whether CCyreactivity (CO2-R) in different regions of
the CNS is uniform or not.6-7 '3 '6 Recently Meyer et
al17 stated from stable xenon-CT measurements that
ICBF of both gray and white matter decreased "diffusely and homogenously throughout the brain," although they registered a 3.9% flow reduction/mmHg
PaCO2 change in occipital cortex but only a 2.6% flow
reduction/mmHg PaCO2 change in occipital white
matter.
For these reasons the present study was designed to
determine the quantitative response of ICBF to PaCO,
From the Neurologische Universitatsklinik Heidelberg.
Address correspondence to: Dr. R. v. Kummer, Neurologische Universitatsklinik, Voss-Str. 2, D-6900 Heidelberg, West-Germany.
Received January 6, 1983; revision accepted June 22. 1983.
change in gray and white matter as well as in the deep
nuclei of the brain. The hydrogen clearance technique
was chosen for lCBF-determination because this method enables direct and repeated measurements. As previous observations18 l9 and preliminary data of this
study showed,20 the vascular reactivity is not impaired
by small hydrogen sensitive electrodes. To minimize
and measure any possible influence of tissue trauma, in
this study the electrodes were implanted chronically
and the CO2-R was repeatedly determined over a period of 12 weeks.
Methods
The experiments were carried out in 6 cats of either
sex within the weight range of 2.4 to 3.7 kg. Anesthesia was induced with sodium pentobarbital (30 mg per
kg) and maintained with 70% N2O-30% O2-gas via an
endotracheal tube. The animals were paralyzed with
pancuroniumbromide administered intravenously, repeated as necessary. Ventilation was maintained by a
Schuler pump. Where the PaCO2 was to be raised, this
was done by adding CCygas to the input of the pump.
Systemic arterial blood pressure and central venous
pressure were recorded continuously via polyethylene
catheters inserted into a femoral artery and vein and
connected to Statham pressure transducers. PaO2,
109
RELATIONSHIP BETWEEN LOCAL CBF AND PACOj/Kummer
PaCO 2 , and pH were measured intermittently before,
during and after each lCBF-determination. An electric
blanket was used to maintain body temperature.
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ICBF-determination
ICBF was measured at 6 sites of the cat's brain
simultaneously by means of the hydrogen clearance
method.21 The measuring circuit consists of 6 epoxy
and glass insulated platinum wire electrodes with a
bared conical tip of 0.3 mm length and 0.2 mm diameter, a subcutaneous AgAgCl reference, six separate
amplifiers (Nanoamperemeter Knick) and an eightchannel pen recorder (Rikadenki). The electrodes were
introduced stereotactically after fixation of the animal's head in a stereotactic apparatus (David-KopfInstruments). Stereotactic placements were calculated
from the atlases of Reinoso-Suarez.22 The electrodes
were inserted into cortex, subcortical white matter and
caudate nucleus of each hemisphere and fixed to the
skull by dental cement. Great care was taken to avoid
any bleeding into the subarachnoidal space. ICBF
measurements were carried out on 4 experimental days
2 to 3 hours after surgery, one week, four weeks and 12
weeks later. Postoperatively and between the days of
ICBF determination the animals were housed in cages
and closely observed. Routinely they were given Ampicillin (40 mg per kg) daily for three days to prevent
infection.
Hydrogen gas was administered via the input of the
ventilation pump so that the hydrogen concentration of
the inhaled gases was 5-10% and the O2 concentration
was not altered. In each measurement hydrogen was
allowed to come to a saturation equilibrium during an
inhalation time of 15 to 20 min.lCBF was calculated
from the clearance curve using the height-over-area
formula of Zierler.23 The partition coefficient for hydrogen has only been determined in kidney tissue
where it is close to unity.21 Therefore it is assumed to
be 1 from brain.14
At the end of the study the brains were carefully
sectioned to confirm the electrode's position and to
observe any tissue alterations.
electrodes in each animal on each day over the range of
PaCO2 values observed on that day. By this 36 successful regression lines were obtained postoperatively,
34 after one week, 36 after four weeks and only 30
after 12 weeks because one cat lost the cranial attachment after 5 weeks so that further ICBF measurements
were not possible.
From trie regression lines absolute CO2-R was computed, defined as the change in ICBF divided by the
change in PaCO2. lCBF^ was obtained by reading off
the blood flow corresponding to a PaCO2 of 40 mmHg.
Percent ICBF change was computed from the equation
percent ICBF change =
1CBF
~
1CBF
4Qy ioo
where ICBF was obtained from the actual measurement.
Relative CO2-R was defined as percent ICBF change
divided by the PaCO2 difference from 40 mmHg.
The data were analyzed by paired t tests and the 0.05
level was accepted as significant.
Results
The condition of 617 ICBF determinations are given
in table 1. The postmortem brain examination revealed
that in two cats the caudate nucleus electrodes did not
reach the desired region and were localized in white
matter.
Table 2 shows the mean ICBF of each region under
different conditions. A linear response (p < 0.05) of
ICBF to PaCO2 was obtained from 19 of 36 electrodes
2 to 3 hours postoperatively, from 27 of 35 electrodes
one week later, from 26 of 36 electrodes 4 weeks after
surgery and from 19 of 30 electrodes 12 weeks after
electrode implantation.
Data Analysis
On each of the four experimental days ICBF measurements were repeated 3 to 7 times so that a regression line could be fitted to the raw data of each of the 6
TABLE 1 Conditions of ICBF-measurements in Cortex, Caudate
Nucleus and White Matter of the Cat's Brain
ImplanMaBP
PaCO2
(mm Hg) (mm Hg). No. of measurements in
tation
period mean ± SEM range Cats C NC WM Total
141±14
52 33 69 154
2-3 h
27-80
6
1 week
150±22
19-93
60 36 71 167
6
4 weeks 144±14
19-65
58 36 77 171
6
42 24 59 125
12 weeks 145±14
21-96
5
Total
212 129 276 617
6
C = cortex
CN = caudate nucleus
WM = white matter
20
40
60
80
100
l per lOOg m m ]
FIGURE I. Absolute COi-reactivtty versus ICBF40 in the cat's
brain. The equation of the regression line is y = 0.02x + 0.22,
r = 0.71 (p < 0.01). Each data point represents the averaged
value of each implanted electrode (n - 36) which was obtained
from the regression analysis of4 days when ICBF was measured
after different periods of electrode implantation.
110
TABLE 2
STROKE
*ICBF in <"ortex.
1
MaBP
(mm Hg)
PaCO,
(mm Hg)
160
27
160
120
hours
ICBF (ml/100 g/min)
WM
NC
C
1 week
MaBP
(mm Hg)
PaCO 2
(mm Hg)
Downloaded from http://stroke.ahajournals.org/ by guest on July 31, 2017
4
5
6
C
NC
WM
35
45
14
72
118
24
70
79
135
31
67
—
20
160
135
29
62
—
19
150
135
28
63
—
21
160
48
—
170
28
45
—
160
19
52
—
85
20
36
23
22
24
25
36
29
49
16
44
16
145
80
54
94
44
160
35
44
56
22
165
155
3
ICBF: (ml/100 g/min)
28
50
44
32
26
93
27
47
28
36
66
160
2
15, No 1, JANUARY-FEBRUARY 1984
Caudate Nucleus
,
and WhiteMatter after Different Periodsof Electrode Implantation
Implantation period
2-. i
Cat
VOL
145
51
82
—
38
170
150
47
76
—
38
140
37
53
25
18
48
35
14
142
—
51
—
92
—
53
—
106
135
40
140
32
69
105
31
160
54
43
53
23
29
45
68
23
108
75
73
90
35
28
45
66
23
128
29
21
34
II
115
20
18
27
11
32
130
51
120
135
140
145
33
44
52
63
180
32
59
55
160
48
128
102
103
190
40
64
59
31
160
41
93
94
118
185
43
63
55
43
160
33
69
84
132
185
40
55
49
32
150
29
54
62
100
130
38
32
83
46
120
72
58
66
34
125
72
46
104
46
120
68
56
53
32
125
49
38
104
44
120
28
15
18
10
125
36
31
82
36
120
22
17
15
9
120
36
28
87
34
145
65
76
—
46
160
42
39
—
21
160
59
67
—
52
150
65
62
—
43
145
44
40
—
33
150
72
81
—
53
150
40
35
—
30
130
22
23
—
14
155
31
28
—
15
• I C B F I represents the mean value of each reei(an measured bv 1-4 electrodes
C = cortex
CN = caudate nucleus
WM = white matter
To examine the relationship between lCBF^ and
absolute CO2-R the values of lCBF^ and absolute CO2R obtained from the regression analysis of all days
were averaged for each electrode and plotted against
each other (fig. 1). As figure 1 shows, absolute CO2-R
increases with increasing lCBF^. With a correlation
coefficient of 0.71 the relationship is considered to be
linear (p < 0.01).
Figure 2 shows the linear relationship between percent lCBF-change (lCBF^ = 100%) and PaCO2 after
different periods of electrode implantation from 2 to 3
hours until 12 weeks. To compare the individual relative CO2-R data from the cat which was followed only
for 4 weeks were rejected. The mean relative CO2-R of
all measuring points in 5 cats was 2.33 ± 1.33 %/
mmHg 2 to 3 hours after surgery, 2.79 ± 0.76 %/
mmHg after one week, 2.77 ± 1.38 %/mmHg after 4
weeks and 2.61 ± 1.57 %/mmHg after 12 weeks. The
slight increase of relative CO2-R during the first week
was not significant (p > 0.05). No significant change
was registered over the 12 week period.
Figure 3 shows the linear relationship between percent lCBF-change (lCBF^ = 100%) and PaCO2 in
cortex, caudate nucleus, and white matter. The mean
relative CO2-R was 2.37 ± 1.70 %/mmHg in cortex,
2.17 ± 1.30 %/mmHg in caudate nucleus, and 2.64
± 1.08 %/mmHg in white matter. No significant differences were found between cortex and caudate nu-
RELATIONSHIP BETWEEN LOCAL CBF AND PACOJKummer
TABLE 2
111
(Continued)
Implantation period
4 weeks
MaBP
(mm Hg)
12 weeks
1CBF (ml/100 g/min)
C
NC
WM
Downloaded from http://stroke.ahajournals.org/ by guest on July 31, 2017
MaBP
(mm Hg)
155
160
165
160
PaCO 2
(mm Hg)
34
44
32
21
135
160
155
150
155
42
38
12
10
59
70
64
49
44
75
68
35
32
41
68
47
33
30
45
39
19
16
—
—
—
18
30
41
17
17
145
140
150
130
115
160
160
155
150
150
140
PaCO2
(mm Hg)
49
57
65
60
53
43
50
51
31
29
30
66
90
103
92
91
45
48
59
46
49
46
72
44
81
85
70
—
—
—
—
—
—
25
32
39
35
30
25
34
45
20
21
18
140
160
140
140
54
50
23
24
70
68
27
27
116
86
32
31
155
155
160
160
155
135
120
120
120
38
62
50
36
78
64
58
36
32
80
95
82
65
60
73
74
33
29
160
150
140
130
140
43
58
45
19
21
40
69
71
42
32
—
cleus (p > 0.2), cortex and white matter (p > 0.8), or
between caudate nucleus and white matter (p > 0.6).
Discussion
This paper presents long term observation of local
vascular responses to altered arterial carbon dioxide
tension. Before proceeding to the results the method of
1CBF determination used requires discussion. It should
be critically examined whether or not vascular reactivity is impaired by technical problems due to chronically implanted electrodes or by tissue alterations in the
vicinity of the electrode's tip. Also the possible influence of anesthesia on CO2-R must be considered. Few
studies are available concerning the influence of
chronic electrode implantation on vascular reactivity.
It has been shown that hydrogen electrodes function
1CBF (ml/100 g/min)
WM
C
NC
27
32
31
32
33
37
37
38
21
25
24
20
40
47
73
31
25
42
58
76
30
32
—
—
—
—
—
25
17
52
11
16
130
120
140
150
80
96
35
25
55
70
26
16
59
70
31
24
25
35
13
9
124
130
152
153
70
45
27
26
92
60
21
18
83
71
24
19
48
34
12
11
130
125
150
151
72
51
35
36
108
93
27
39
—
—
—
53
51
15
22
normally some weeks24"27 and even 30 months28 after
implantation. CO2-R was observed directly after electrode implantation15-l8 and until 2 weeks later.23-27 In
one goat a gradual decrease in flow was reported over
five weeks.26 No significant change in the flow rates
was registered in rats over a six-week implantation
period.24 Preliminary data of this study showed that
autoregulatory capacity is not impaired during the implantation period of 12 weeks, but 1CBF decreases
significantly in some of the examined regions during
the first week after implantation.20 The present investigation does not detect a significant alteration of the
relative CO2-R during the observation time of 12
weeks but cannot exclude the possibility that in all
measurements performed the CO2-R might be blunted
by anesthesia and/or by the applied technique. Con-
STROKE
112
B
A
/
100
60
j
/
'•
80
/ .
40
j
20
0
J
J•
J
4>
* J•
•
c
feioo
60
Downloaded from http://stroke.ahajournals.org/ by guest on July 31, 2017
20
j
-20
I*
y•
/•
*
7
20
/
• j.
*/
/
* • /"
./
o
~ 80
-40
fr
D
0
7
1
•'•4
-20
*
:
40
60
80 100
V
20
40
60
80 100
FIGURE 2. Percent ICBF change versus PaCO? 2 to 3 hours
after electrode implantation (A), one week later (B), 4 weeks
later (C), and 12 weeks later (C). The equations of the regression lines are A: v = 2.18x - 84.2, r = 0.90 (p < 0.01), B: v
= 2.71x - 106.1, r = 0.97 (p < 0.01), C: v = 2.61.x 102.9,r = 0.91(p<0.01),D:y
= 2.54x - 96.4, r = 0.92 (p
< 0.01). Each data point represents the mean value from 4 to 6
simultaneously measuring electrodes.
cerning the quantity of relative CO2-R only little comparable data is available from the literature. In the
brain," as well as in the spinal cord10 of dogs, 100%
increase in blood flow was found when PaCO2 was
changed from 40 to 80 mmHg, which means a relative
CO2-R of 2.5 %/mmHg. This is in very good agreement with the results of this report, which seems remarkable with respect to the different species and
methods of CBF determination.
Thus, it can be stated that early measurements after
electrode implantation might produce unstable ICBF
data, but vascular reactivity is not influenced by the
hydrogen clearance technique if small electrodes are
used.
The various methods and equations which have been
used to describe the PaCO2-CBF-relationship are listed
in table 3. Within the interval 20 to 80 mmHg a linear
correlation was found when CBF-change was expressed in percent of CBF^. 4 5 - 1 0 If absolute CBF was
correlated to PaCO 2 , an exponential function 1 - 8 - 912
and also linearity2 3- " were described.
These findings are not contradictory if the methods
of each investigation are considered. In the studies
VOL
15, No
1, JANUARY-FEBRUARY
1984
cited here the slope of the CBF-PaCO2-correlation was
calculated from mean CBF values of different animals
or humans. This, however, must lead to different results, if absolute CO2-R does depend on individual
CBF which is indicated by the present study. An exponential function of the CBF-PaCO2-relationship would
then be obtained by the variability of individual CBF
and linearity could be due to a homogenous CBF in the
studied subjects or to a small CO2-interval.3 Thus, to
compare CO2-R interindividually or interregionally
CBF-change should be expressed in percent of a definite CBF value, e.g. CBF^.
Observations of the local vascular reactivity in subcortical structures are rare and contradictory7-13~17-w-M
apparently due to the difficulties in quantification of
C0 2 -responses and/or to methodical problems.
Calculating ICBF from the two-compartmental
model of isotope clearance CO2-R of white and gray
matter cannot be independently assessed owing to a
shift in the fast clearing compartments at low flow
rates.16 Using the hydrogen clearance method Symon
et al15 found a percent CO2-R reactivity of 2.02%/
mmHg in the putamen, 2.31 %/mmHg in cortex and
3.44 %/mmHg in white matter and revealed no significant differences between gray and white matter. These
values are not strictly comparable to the present results
because they were related to "basal flow" and not to
In the caudate nucleus of 6 cats CO2-R was tested by
Fieschi and his colleagues.18 The absolute CO2-R calculated from their data shows a considerable variation
between 1.85 and 7.47 ml/100 g per min/mmHg. It
must be considered, however, that these absolute CO2R values base on two CBF determinations at different
PaCO2 only, which might give unstable results. Flohr
et al7 studied the CO2-R in various parts of the cat's
CNS by means of the 131-I-albumin method. They
found considerable differences in absolute CO2-R. Re-
uo
c
v
120
WM
CN
.
"•/
no
'if
•
• /
.
/
'
7:
•7
i
•}
»
S 0
-20
-to
-60
0
,'/
•
20
«)
/
/ •
|to
:
/
•f
si
*
60
80
CO
20
U>
60
80
DO'
0
20 tO 60 80 B0
P > C O J [mmHj]
FIGURE 3. Percent ICBF change versus PaCO2 in cortex (C),
caudate nucleus (CN), and white matter (WM) of the cat's
brain. The equations of the regression lines are: C: y = 2.54x
- 96.5, r = 0.90(p<0.01), CN:y = 2.32x - 92.6, r = 0.92
fp < 0.01), WM: v = 2.63x - 103.2, r = 0.93 (p < 0.01).
Each data point represents the mean value of the individual
region measured simultaneously by 2 to 4 electrodes.
RELATIONSHIP BETWEEN LOCAL CBF AND
PACO7/Kummer
113
TABLE 3 Quantitation of CO2 Reactivity in the Literature
Ref
no.
CBF-determinations
Species
1
man
2
monkey
3
man
4
dog
n
Technique
n
PaCO2
range
(mm Hg)
PaCO2-CBF-relationship
N2O
49
20-60
exponential
thermistor-flowmeter
81
5.3-418
asymmetric sigmoid distribution, between PaCO2 =
20-80 mm Hg approximately linear
13
85-Kr
24
19-56
linear, CBF = 1.37 PaCO2-5.08
41
85-Kr
302
10-100
sigmoid curve of percent CBF-change (CBF^ =
100%). Linearity between PaCO2 = 25-75 mm
Hg
8
6
(A-V)o2
Downloaded from http://stroke.ahajournals.org/ by guest on July 31, 2017
7
cat
15
8
cat
18
131-I-albumin
85-Kr
9
man
20
10
dog
9
95
90
linearity (r = 0.75) of percent CBF-change (controlCBF = 100%)
111
20-40
20-80
133-Xe, in).
44
19.5-63
133-Xe, direct injection
50
linearity in different CNS-regions
exponential logCBF = 0.0056 PaCO,-O.I27, r =
0.578
exponential, the relative CO2-reactivity was found
independent of the height of CBF
20-140
linearity of percent change in spinal cord flow
(SCBFJO = 100%), r = 0.87
11
monkey
23
H2-15-O
51
15-78
linearity
12
man
16
133-Xe, inj.
71
20-55
2 exponential functions merging into each other
calculation of their data reveals a rather uniform relative CO2-R between 2.47 and 3.72 %/mmHg.
Thus, in agreement with former studies, the present
results confirm that relative CO2 response is not different in various regions of the CNS. This would seem to
support the hypothesis that the CO2 response is due to a
direct effect of PaCO 2 or local tissue pH on arterial
blood vessels of the brain and the spinal cord31 32 and
not mediated through brain stem structures,33 because
identical control of all vasocompartments of the CNS
by one center is hardly possible.
2.
3.
4.
5.
The described uniformity of relative CO2-R means
that absolute C0 2 -responses are greater in better perfused areas, e.g. in gray matter than in white. Thus,
different opinions whether or not CO2-R is different in
various brain regions might be due to different methods
of CO2-R calculation.
6.
It would be of great interest if recalculation of the
CBF-PaCO2-relationship in the extensive literature
published until now could show that relative CO2-R is
about 2.5 %/mmHg also in the conscious man.
8.
In conclusion, this report stresses the importance of
determinating CO2-R in relation to a definite CBF value, e.g. CBF^ to avoid confusion. A valid comparison
of blood flow in different individuals and interregionally cannot be effected until the individual CBF^ has
been determined by repeated CBF measurements under different PaCO 2 .
7.
9.
10.
11.
12.
13.
Acknowledgments
The author acknowledges Miss M. Deiseroth for technical assistance
and Prof. A. Hartmann for his review of the manuscript.
The study was supported by the Deutsche Forschungsgemeinschaft
(Ku 417/1).
References
1. Kety SS, Schmidt CF: The effects of altered arterial tension of
carbon dioxide and oxygen on cerebral blood flow and cerebral
14.
15.
16.
oxygen consumption of normal young men. J Clin Invest 27: 484492, 1948
Reivich M Arterial PCO2 and cerebral hemodynamics. Am J
Physiol 206: 25-35, 1964
Alexander SC, Wollman H, Cohen PJ, Chase PE, Behar M: Cerebrovascular response to PaCO2 during halothane anesthesia in
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Cerebral Infarction Associated with Lupus
Anticoagulants — Preliminary Report
ROBERT
G.
HART,
M.D.,*
VINCENT
T.
MILLER,
VERA BRIL,
M.D.,t
BRUCE
M.
COULL,
M.D.,t
AND
M.D.§
SUMMARY Hypercoagulability may contribute to stroke in young adults. Lupus anticoagulants (LA)
were identified in six patients (4%) of 145 young adults with cerebral infarction. The clinical features of the
6 patients in this survey plus an additional patient from another institution with LA-associated stroke are
presented. Four had systemic lupus erythematosus and 3 had idiopathic LA; all had mild thrombocytopenia. In 2 patients, no other conditions associated with stroke were discovered after thorough evaluation.
Recurrent arterial thrombosis occurred in 4 of 7 patients during an average of two years of follow-up.
Evidence suggests that inhibition of prostacyclin formation may occur with LA, promoting a prothrombotic state.
Stroke Vol 15, No I, 1984
LUPUS ANTICOAGULANTS (LA) are acquired IgG
or IgM immunoglobulins which inhibit coagulation by
interfering with the phospholipid portion of the prothrombin activator complex. 1 2 Although it initially
described in patients with systemic lupus erythematosus (SLE) 30 years ago, they have been associated with
the use of phenothiazines, non-SLE autoimmune disease, neoplasms, and drug-induced lupus as well as
From the Department of Medicine (Neurology),* University of Texas
Health Science Center, San Antonio, Texas; the Department of Neurology,t Northwestern University Medical School, Chicago, Illinois; the
Department of Neurology,t Oregon Health Science University, Portland, Oregon; and Toronto General Hospital,§ Toronto, Ontario, Canada.
Address correspondence to: Robert G. Hart, M.D., Department of
Medicine (Neurology), University of Texas Health Science Center,
7703 Floyd Curl Drive, San Antonio, Texas 78284.
Received March 3, 1983; revision accepted June 21, 1983.
occurring idiopathically.1"5 The laboratory hallmark is
a prolonged partial thromboplastin time (PTT) which
fails to normalize when affected plasma is mixed with
normal plasma. Additionally, mild thrombocytopenia
and a false-positive VDRL are often associated with
LA.
Despite their function as in vitro anticoagulants, LA
are, paradoxically, most often associated with thrombosis and not abnormal bleeding.6 Mueh et al recently
reported thrombotic events in eight of 35 patients with
LA. 4 Most clinical events have involved venous
thromboembolism, but arterial thrombosis with attendant stroke (3 patients) and TIA (3 patients) has been
reported.2-4-7-9
We report the clinical features of cerebral infarction
associated with LA occurring in seven young adults.
Of these patients, 6 were identified in a retrospective,
population-based survey of 145 young adults with ce-
Local vascular response to change in carbon dioxide tension. Long term observation in the
cat's brain by means of the hydrogen clearance technique.
R von Kummer
Stroke. 1984;15:108-114
doi: 10.1161/01.STR.15.1.108
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