(Stroke. 1996;27:720-728.)
© 1996 American Heart Association, Inc.
Articles |
Alterations of Regional Cerebral Blood Flow and Oxygen Saturation in a Rat Sinus-Vein Thrombosis Model
From the Institute for Neurosurgical Pathophysiology, Johannes Gutenberg University, Mainz, Germany.
Correspondence to Univ-Prof Dr med Oliver Kempski, Institute for Neurosurgical Pathophysiology, Johannes Gutenberg University Mainz, Langenbeckstr 1, 55101 Mainz, Germany.
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Background and Purpose The pathophysiology of sinus-vein thrombosis (SVT) in patients and experimental animals is still poorly understood. This study was designed to examine and further elucidate the pathophysiological sequence of events, especially the relationship between local and regional blood flow and hemoglobin oxygen saturation (HbSO2) detected at identical locations. The use of both parameters as outcome indicators should be compared.
Methods SVT was induced by ligation of the superior sagittal sinus (SSS) and slow injection of kaolin-cephalin suspension into the SSS in rats. Regional cerebral blood flow (rCBF) was assessed by laser-Doppler flowmetry together with regional HbSO2, which was measured by a microspectrophotometric technique at 48 identical locations for 90 minutes after SVT using a scanning technique. Fluorescence angiography was performed before and 30 and 90 minutes after SVT induction. After 48 hours the animals were killed for histology.
Results The fluorescence angiographic findings could divide animals into three groups: (1) group A, with a solitary SSS thrombus (n=8); (2) group B, with a thrombosis of SSS and cortical veins (n=10); (3) group C, animals that had undergone sham operation (n=5). Decreases of rCBF and HbSO2 and brain damage were seen in group B but not in group A. The reduction of local HbSO2 preceded the flow decrease after sagittal sinus ligation but before thrombosis. Blood pressure in group A was found to be significantly higher after SVT than in groups B and C.
Conclusions The brain with acute extension of a thrombus from the SSS into cortical veins experiences a critically reduced supply of blood and oxygen. CBF, local HbSO2, and repeated angiography can be helpful monitors for the early detection of critical conditions after SVT. Local HbSO2 has a greater sensitivity to predict outcome than lCBF. Moreover, therapies directed to improve perfusion pressure or reduce vascular resistance may open further therapeutic windows during SVT progression.
Key Words: cerebral blood flow • cerebral thrombosis • cerebral veins • microcirculation • rats
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After years of research on cerebral ischemia from arterial obstruction, growing attention has been paid recently to the study of cerebral injury subsequent to venous circulation disturbances.1 2 3 4 5 6 7 SVT is increasingly recognized as a much more frequent neurological disorder than it was in earlier days. SVT is often misdiagnosed because of the wide spectrum of its clinical manifestations: the clinical symptoms as well as the prognosis of SVT observed in patients and animal experiments are quite variable, ranging from no symptom at all to severe venous infarction. Thrombosis of the SSS may be relatively innocuous, especially if only its anterior end is thrombosed. On the other hand, the prognosis of cerebral venous thrombosis accompanied by severe hemorrhagic infarction in patients is still rather poor, and its suitable treatment and prevention remain controversial.8
Recent publications on experimental SVT have well documented that SVT causes brain damage only if draining cortical veins are involved.1 2 3 4 6 7 The monitoring of CBF has been useful for predictions of brain damage subsequent to SVT and cortical vein occlusion.5 7 Now, in a next step, the relationship between local and regional CBF and HbSO2 detected at identical locations should be evaluated. The use of both parameters as outcome indicators should be compared.
There are various animal models for SVT,1 2 3 4 5 6 7 9 but the rat model with a combination of SSS ligation and the injection of a thrombogenic material, kaolin-cephalin suspension (a reagent available for the partial thromboplastin time reaction), is currently best established. The model produces a clinically relevant SVT, not through simple mechanical obstruction but rather a true thrombotic process. It also permits long-term survival, which makes the long-term assessment of histological damage possible. Two recent SVT experiments using this model demonstrated that it regularly exhibits a dichotomy in histopathological findings that correlates well with changes in lCBF during the experiment and results in a similar percentage of animals (approximately 50%) with morphological manifestations after SVT induction.2 7
The goal of the present experiment was to investigate the pathophysiological changes occurring in the brain after SVT, especially the association of ischemia, local HbSO2, and subsequent outcome. To do so, rCBF was measured by LD flowmetry and local HbSO2 with a microspectrophotometric approach and a scanning technique. The advantages of the microspectrophotometric technique include the capability for continuous monitoring in living animals with minimal damage to the tissue.10 11 12 13 Moreover, the new "scanning" technique,14 15 16 17 which moves a probe attached to this system by a computer-controlled micromanipulator to multiple locations in a cranial window, provides lCBF recordings and corresponding local HbSO2 from identical locations. Additionally, this technique makes it possible to use the LD technique for the detection of low-flow areas14 and to assess rCBF from these lCBF data.17
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Materials and Methods |
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The present study was conducted according to the German animal protection legislation and was reviewed by the regional ethics committee (Bezirksregierung Rheinhessen-Pfalz, AZ 177-07/93120).
Twenty-three male Wistar rats (260 to 370 g body weight)
were premedicated with 0.5 mg atropine. Anesthesia was
introduced with ether and continued by
intraperitoneal injection of chloral hydrate (36
mg/100 g body wt). During the experiments, spontaneous ventilation was
maintained, and rectal temperature was controlled at 37°C by means of
a feedback-controlled homeothermic blanket control unit (Harvard).
Polyethylene catheters were inserted into the tail artery and the right
femoral vein under an operating microscope (OP-microscope; Zeiss). The
arterial line served for continuous registration of
arterial blood pressure via a pressure transducer (Gould
134615-50) and for blood gas analysis.
PaO2,
PaCO2, and arterial pH were
measured with an ABL3 blood gas analyzer (Radiometer). The
venous line was used for administration of fluid and drugs. Each rat
was mounted on a stereotaxic frame (Stoelting). After a
2.0-cm midline skin incision was made, a cranial window (9x6 mm) was
made between the coronal and lambdoid sutures bilaterally with a
high-speed drill under the operating microscope. During the
craniotomy, the drill tip was cooled continuously with
physiological saline to avoid thermal injury to the
cortex. The dura was left intact, and the SSS and bilateral
parasagittal cortex were exposed (Fig 1
). Then,
fluorescence angiography was performed for examining
epicortical vessel structures. A 2%
Na+-fluorescein solution (0.5 mL; E. Merck) was
injected intravenously. A photomacroscope with
magnification from x5.8 to x35.0 (M 420; Wild) furnished with a 50-W
mercury lamp and fluorescence filter (I2; Leitz) was used for
fluorescence angiography, which was carried out before and 30
and 90 minutes after induction of SVT. The images were recorded on
videotape (HS-S5600E[RS], Mitsubishi), permitting a careful
reevaluation. To minimize damage by fluorescence excitation,
illumination of dura and underlying cortex was restricted to
angiography.
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lCBF was measured using a Vasomedics laser flow blood perfusion monitor (model BPM 403a) with a 0.8-mm needle probe. lCBF is expressed in LD units. The LD system used has a reproducibly low biological zero,17 and with the scanning technique described below data from individual animals and locations may be compared.7 14 16 17 The local HbSO2 in percent was measured with the EMPHO II SSK-BB (Bodenseewerk Gerätetechnik GmbH). The EMPHO monitor consists of four modules: a light source, a micro-lightguide, the detector, and a computer.18 19 Parallellized light from a xenon high-pressure lamp is transmitted to the tissue surface by a central fiber surrounded by a hexagon of six detecting fibers. Light transmitted by these detecting fibers passes a fast rotating interference band-pass filter disk (502 to 628 nm) and then illuminates a photomultiplier. The raw spectrum thus obtained is corrected on-line with the dark spectrum and with the spectrum obtained from excitation light reflected from a mirror at a set distance.19 The response spectrum is used for the evaluation of the tissue spectra from which local HbSO2 is calculated. To do so, the spectra are digitized in 2-nm increments from 502 to 628 nm. The relative amounts of oxyhemoglobin and deoxyhemoglobin normalized for light scattering are estimated as parameters using an iterative best-fit procedure based on the theory of Kubelka and Munk.20 These are relative concentrations because of light scattering, but they do permit calculation of the percentage of oxyhemoglobin saturation.19 20
lCBF and HbSO2 were measured at 48 (8x6) identical locations in a scanning procedure by means of a computer-controlled micromanipulator. Thus, the random registration of 48 individual measurements results in one scanning procedure with information from 48 different locations, each at a distance of 400 µm.
The SSS was ligated first rostrally and then caudally close to the
confluens sinuum using 9-0 prolene sutures, without damage to the
adjacent brain tissue. After lCBF and HbSO2 were scanned, a
Hamilton microsyringe with a 27-gauge needle attached to a
micromanipulator was used to puncture the SSS between the two sutured
points just in front of the dorsal ligature. A kaolin-cephalin
suspension (100 µL, partial thromboplastin time reagent;
Boehringer Mannheim) was injected into the SSS over 5 minutes
in fractionated 10-µL portions at 30-second intervals (Fig 1
).
Thereafter, the multiple scanning was repeated at identical coordinates every 15 minutes for 90 minutes. Subsequently, after the third fluorescence angiography the needle was removed without or with minor bleeding, the resected bone flap was repositioned, and the skin wounds were closed. The rats were returned to individual cages and allowed free access to water and food. Two days after the operation, clinical manifestations were observed, and the rats received an injection of 2.0% Evans blue solution (1 mL/kg). After 1 hour, the rats were submitted to perfusion fixation with 4% paraformaldehyde under general anesthesia with chloral hydrate. The brain was then removed from the skull. Coronal brain blocks from the parietal cortex were embedded in paraffin. Sections were prepared and stained with hematoxylin and eosin.
In addition, five rats served as sham-operated controls, which received only craniotomies without SSS ligation or injection of kaolin-cephalin.
Data are expressed as mean±SD for physiological variables and as mean value±SD of the median lCBF and HbSO2 from the 48 data sets from each rat. ANOVA for multiple comparison or the Mann-Whitney rank-sum test was used for between-group comparisons. Time sequences were evaluated by ANOVA followed by Dunnett's test for repeated measures. Statistical significance was accepted at an error probability of P<.05.
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According to the pattern of the fluorescence angiography, which provided information on the quality of venous blood flow and the extension of the growing thrombus, animals could be divided into three groups: (1) group A, in which the SSS was occluded without any sign of cortical vein thrombosis (n=8); (2) group B, in which the thrombus extended from the SSS into cortical veins (n=10, Fig 2A
and 2B); and (3) group C, animals that had undergone sham operation
(n=5). The third angiography regularly revealed a spotty extravasation
of fluorescein in the parasagittal cortex in group B
only.
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Physiological variables showed no significant
changes of blood gases (eg, PaO2,
PaCO2, and pH) (Table 1)
before and after SVT induction or among the groups. Mean
arterial blood pressure was not significantly changed by
thrombosis induction and thereafter stayed at an approximately 15%
higher level in group A compared with groups B and C (P<.05
from 15 to 90 minutes; Table 2).
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The calculation of median rCBF values from the 48 locations in each
animal demonstrated no change of rCBF in groups A and C comparing
groups or estimated by ANOVA for repeated measures. In group B, rCBF
significantly decreased after the injection of kaolin-cephalin
suspension compared with group A (P<.01). The control rCBF
value of group B was 44.2±13.9 LD units, and the maximal and highly
significant drop was to 21.5±7.5 LD units by 15 minutes after SVT
induction. Thereafter, a gradual incomplete recovery was found, with
29.9±11.7 LD units after 90 minutes (Fig 3). In group C
(sham operation), rCBF was 48.6±9.7 LD units at the beginning and then
remained constant, with 51.6±4.9 LD units at the end of the
experiment.
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), there were no
significant changes. In group B (
), however, rCBF significantly
decreased after 15, 30, and 45 minutes (*P<.05) and,
compared with rCBF in group A, after injection of the
kaolin-cephalin suspension (P<.01). a, Ligation of SSS;
b (shaded bar), injection of kaolin-cephalin suspension.
The median of the local HbSO2 values collected at the 48
locations in each animal revealed no difference of HbSO2 in
groups A and C either between these groups or estimated by ANOVA for
repeated measures. Under control conditions before SVT induction, group
A had a regional HbSO2 of 56.2±9.1%; 90 minutes after
SVT, it was measured at 52.5±5.1% (Fig 4). In group C
(sham operation), regional HbSO2 was 49.1±9.5% at the
beginning and stayed at that level throughout the experiment, yielding
50.4±8.4% at the end. In group B, however, HbSO2 had
already significantly decreased after the ligation of the SSS. Compared
with group A, the decrease was significant after 45 minutes until the
end of experiment (P<.05). The maximum drop was from
51.7±7.0% before SVT to 35.9±11.2% after 90 minutes, which is
significant (Fig 4).
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The fact that repeated measurements were collected at 48 identical
locations in each animal allowed us to study
oxygenation changes at these spots during the course of
the experiment. For data evaluation, control HbSO2 values
were subtracted from values sampled at given time points after SVT, and
frequency histograms were calculated. The histograms display a gaussian
distribution, with a mean change of 0.01±8.3% after ligation in group
A (ie, no change; Fig 5a, white bars) and a minor
-2.8±9.7% reduction at the end of the experiment (Fig 5f, white
bars). In group B, however, a -4.8±9.3% shift of the
distribution to the left (ie, toward lower saturation values) was
already found after SSS ligation (Fig 5a, black bars;
P<.001 versus group A). With progressing time, the shift
became more evident, reaching a mean reduction of -16.1±13.2%
at the end of the experiment (Fig 5f, black bars).
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There were no differences between the distributions of lCBF and local
HbSO2 in groups A and B before induction of SVT (Figs 6a and 7a). After SSS ligation,
HbSO2 decreased only in group B, although rCBF was still
unchanged (Fig 7b). With progressing time after SVT, rCBF decreased
together with regional HbSO2 in group B but not in group A
(Fig 7). At the conclusion of the experiment, 90 minutes after SVT
induction, the number of measuring points with low CBF (<20 to 30 LD
units) and low local HbSO2 (<30 to 40%) had substantially
increased (Fig 6b, left), whereas the distributions in group A did not
change (Fig 6b, right).
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A detailed analysis of the sequence of events after SVT
induction is possible with an adequate spatial and temporal resolution
only if individual cases are analyzed. Fig 8
illustrates the changes of lCBF and HbSO2 immediately after
SSS ligation in a case with subsequent thrombosis progression. As
easily recognized, lCBF is reduced only in the immediate vicinity of
the underlying vein, whereas more distant regions even display moderate
hyperperfusion (Fig 8a). Similar perfusion patterns were often
observed. Fluorescence angiography regularly revealed complex
collateral pathways at these locations, surprisingly often associated
with flow reversal. With the current techniques, however, it was not
possible to link these angiographic data with the LD scan information
in a statistically satisfactory way. Respective studies are under way.
The findings may explain why median flow values remained unaffected at
this time point. HbSO2, on the other hand, was
moderately reduced in the whole region (Fig 8b). Interestingly, the
lowest readings were seen in the more proximal venous sections, which
may serve as another indication that flow reversal occurred.
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Taken together, the data are consistent with a severe
disturbance of the microcirculation including flow reversal,
which explains the unchanged or moderately reduced median rCBF, whereas
saturation was reduced at a very early point in time. Only later, after
the thrombus had expanded, was the reduction of rCBF as prominent as
the saturation decrease. Fig 9 compares flow and
saturation data 90 minutes after SVT induction in the most severe case.
Here, HbSO2 has reached ischemic values at some
locations. lCBF, on the other hand, was low but clearly remained above
the biological zero. Although the large veins were completely occluded,
some collateral flow appeared preserved. It should be stressed that in
most other cases and even in most individual scanning points
HbSO2 did not decrease that far (Fig 6).
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Histologically thrombotic material was routinely found in the SSS, and thrombosed intraparenchymal vessels are typical for group B. The sham-operated rats showed no histological change at all. The rats from group A revealed no or mild histological change such as slight brain edema. Bilateral parasagittal infarction is characteristic for group B, and such alterations already have been reported for this model.2 Petechial hemorrhage around the dilated capillaries was also observed in some animals, but massive hemorrhages and widespread extravasations of Evans blue were not apparent.
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Discussion |
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Research on cerebral venous circulation disturbances has been limited partly by the lack of animal models that produce consistent venous infarction. There have been several reports on SVT using various animal models.1 2 3 4 5 6 7 9 21 Dogs, cats, pigs, and rats have been used, involving direct SSS occlusion using ligation, ballooning, coagulation, and/or injection of obstructing or thrombotic materials as obstructing techniques. Those models implying a true thrombotic process are more similar to human SVT, and therefore are to be preferred.2 7 A minor problem associated with the rat model used in the present study is the immediate decrease of systemic blood pressure after injection of the kaolin-cephalin suspension. This, however, appears benign, is rapidly reversible, and is not responsible for brain damage from SVT.2 7 Both groups A (without brain damage) and B (with brain damage) had comparable decreases of systemic blood pressure in this study, although the outcome from SVT was different.
The present study has methodological advantages over previous ones because the use of a scanning technique14 15 16 17 for the assessment of lCBF and local HbSO2 allows a detailed analysis of the spatial heterogeneity. CBF assessment by conventional single-spot LD is highly dependent on the localization of the LD probe because of its small spatial resolution (1 to 2 mm3). The accuracy of repeated scans using a stepping motor-driven micromanipulator has been excellent.14 16 17 The analysis of LD data by frequency histograms and cortical mapping represents a useful tool, providing information on the regional CBF variability that is not available from a single stationary probe. In a recent simulation study,17 the number of measurements necessary to assess rCBF by local LD recording has been evaluated, revealing that sample sizes above n=25 are necessary to obtain reliable information on rCBF, a number well surpassed in the present experimental paradigm. Here, the scanning technique was expanded by including HbSO2 assessment from the same locations, a procedure made possible by the similar sampling volumes of both techniques.
There were five major findings in this study. (1) Only animals with the extension of a thrombus from the SSS to the cortical veins after induction of SVT had brain damage. (2) In these cases, regional HbSO2 as well as rCBF decreased after the induction of SVT. (3) The reduction of HbSO2 preceded the flow decrease. (4) A partially preserved flow in individual cortical locations accompanies a critically depressed HbSO2 at that site. (5) Blood pressure of the animals tolerating SVT without brain damage was higher than that of the animals with brain damage. Of these, observations 3 through 5 are quite novel.
Some authors have already reported a decrease of CBF after SVT below the ischemic threshold that occurs only if the thrombus expands from the sinus into bridging and cortical veins.4 6 7 21 Ungersböck et al7 observed a significant decrease of lCBF after ligation of the SSS in the same rat SVT model. Our results are in general agreement with these previous reports. We, in addition, found a significant reduction of local and regional HbSO2. The sole ligation of the SSS does not cause brain damage but would be expected to cause changes of local hemodynamics. Interestingly enough, we found that the reduction of HbSO2 seemed to precede the flow decrease. At this early time point, the two outcome groups—with and without subsequent brain damage—could already be separated, as evidenced by regional HbSO2. Individual variations in the cerebral venous drainage are currently considered to be the most likely reason. Our data underline that at a high spatial resolution, above-threshold flow values may accompany critically low oxygen saturation values. Flow, therefore, in conditions of venous obstruction, appears to be a less sensitive parameter, which is not surprising, since drainage of desaturated blood via complex collateral pathways, although nonnutritive, is also detected as "flow."
One might argue, on the other hand, that the apparent superior
sensitivity of HbSO2 is a technological artifact rather
than a physiological difference. A technological
problem might arise from the fact that the laser flowmeter used
monitors red cell flux at 780 nm, which is not an isosbestic point but
is close to the 760-nm peak for deoxyhemoglobin. Because
HbSO2 changes, and cerebral blood volume is expected to
increase, the flow monitor might be inaccurate under these conditions
and fail to detect a true flow decrease. The flowmeter, however,
calculates red cell flux from red cell velocity and from the ratio of
moving versus nonmoving structures ("volume fraction").
Therefore, red cell velocity, which is determined only from the
Doppler shift and not from absolute signal intensities, should
decrease if red cell flux would be decreased under conditions of a
stable or even increased7 volume fraction signal. If
HbSO2 data are plotted against red cell velocity in a
manner similar to the approach chosen in Fig 6 for HbSO2
and lCBF, the decline of HbSO2 again occurs earlier than
the velocity decrease (data not shown). Since volume fraction does not
change or increases slightly after sinus ligation,7 our
data support the contention that a true
physiological difference is monitored.
Another technological pitfall might arise from the
microspectrophotometric technique used to assess HbSO2.
Although the technique has been used in various organs18
including the brain,19 an exact validation for brain
tissue (eg, using conditions of varied total hemoglobin together with
altered oxygenation) is not available so far. Changes
in light scattering, CSF turbidity, or effects of chromophores other
than hemoglobin might violate some of the assumptions in the theory of
measurement and thereby add unknown error. These possible errors,
however, will only affect the absolute HbSO2 readings or
the variability of the results but not basic findings such as
reductions of HbSO2 below the control level. The decrease
of HbSO2 especially, together with the low lCBF readings
after SVT found in group B (Fig 6d) but not in group A, cannot be
attributed to methodological errors that would be expected to occur in
both groups. Similarly, the observation that HbSO2
decreased after SSS ligation in group B (Fig 7b) cannot be explained by
insufficient validation but must be considered a true phenomenon.
Moreover, the absolute readings collected by EMPHO under control
conditions are very well comparable to data sampled with other
techniques: with a microreflectometric system, Watanabe et
al22 found hemoglobin saturation over capillary regions at
values of 50% to 70%, which changed depending on hematocrit and
inspired oxygen concentrations. Venous oxygen saturation as assessed by
microspectrophotometry in frozen sections showed a high regional
heterogeneity, with mean values of 51.8% or 55.7% in
anterior or posterior cortex of conscious rats.23 The
coefficient of variation (SD/meanx100) was 23, which compares well
with a value of 19 calculated for the present study. With a
three-wavelength spectrophotometric method, Narita et
al24 obtained a regional HbSO2 of
approximately 55%. A minor portion of the HbSO2
readings—and likewise of LD measurements—will derive from
arteries or arterioles. The degree of this contribution, however,
remains small, since the microcirculation and the venous system contain
more than 80% of cerebral blood volume and therefore also contribute
to a similar degree to HbSO2 recordings. Because it
currently is not possible to evaluate the exact contribution of
individual vessel segments to the local HbSO2 or lCBF
readings, we prefer to either study correlations between both
parameters without reference to the underlying
anatomy, as in Fig 6, or express the medians of locally
obtained data as regional HbSO2 or rCBF, respectively.
Recently, Frerichs et al2 demonstrated by electrical
tissue impedance the rapid development of cytotoxic edema after SVT,
more rapid than expected after cerebral ischemia where edema
development can progress only after recirculation or in the penumbra.
In SVT, the uninterrupted arterial blood supply is the
basis for a net influx of water and for early intracranial pressure
changes. Our data illustrate that, in addition, SVT also has a
metabolic component: flow reversal and the decreased
velocity in the microcirculation7 go along with extended
residence times of individual red cells and hence a reduction of the
microvascular HbSO2. It should be emphasized that the
spread of cerebral thrombosis apart from the known macrovascular events
involves changes in the microcirculation that may determine outcome of
individual cases. In most animals with thrombosis progression,
HbSO2 decreased to critically low values in a fraction of
the 48 scanning points relatively early after SVT induction and
remained at that level (Figs 7 and 8). Tissue function will suffer only
if HbSO2 drops below a critical threshold at which the
tissue oxygen supply cannot be maintained via an increased extraction
fraction. Taken together, the cerebral cortex after SVT appears to be a
good model for a penumbralike situation with a critical reduction of
flow and oxygen supply, which may be observed and evaluated
considerably longer than respective cases after arterial
occlusion. It must remain a goal for future studies to establish
critical thresholds of lCBF and HbSO2 by correlating local
histological damage with local
hemodynamic data.
Another significant pathophysiological component, which may vary in individual animals, is cerebral perfusion pressure. Arterial blood pressure of animals without brain damage in group A was approximately 15% higher than that of sham-operated rats and animals with brain damage. This observation confirms earlier data.7 Especially at critical levels of perfusion pressure, the brain is considered to be sensitive to small changes of arterial, venous, or intracranial pressure. Wagner and Traystman25 stressed that in their experiments with variations of venous pressure only animals with a cerebral perfusion pressure lower than 60 mm Hg showed a reduced hemispheric CBF. Similar observations on the effect of varied venous pressures on cerebral autoregulation have been reported by McPherson et al.26 Because the rats in the present experiments were moderately hypercapnic and slightly hypotensive because of the chosen anesthetic regimen, small increases in venous pressure may decrease CBF more in this model than in normocapnic, normotensive patients. This cautionary point should be made before far-reaching conclusions for the clinical setting are drawn.
Still, the question remains why in the present study did blood pressure increase only in subgroup A (animals without brain damage). A better understanding of this intriguing mechanism may open an additional therapeutic window for SVT. In patients, cerebral perfusion pressure should be carefully monitored, and any reduction should be treated. A moderate hypervolume/hypertension therapy as suggested for the treatment of vasospasm27 can be supported only if anticoagulation has been successfully initiated before. Further studies are necessary to examine whether SVT patients could benefit from an increased cardiac output as shown for focal cerebral ischemia.28
In conclusion, a given fraction of experimental animals and probably also SVT patients present with an acute extension of the thrombosis from the SSS into cortical veins. This subgroup has an unsatisfactory outcome and a high risk of infarcts. The kinetics of infarct development are different from arterial obstruction and resemble those seen in the periinfarct penumbra zone. Changes of rCBF, angiographic demonstrations of thrombosis growth, and occurring most early, decreases of regional cortical HbSO2 can be linked closely to outcome after SVT. The assessment of these parameters could be useful in a clinical setting, using near-infrared spectroscopy,12 for example, to monitor early changes and to detect patients at risk after SVT.
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Acknowledgments |
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The authors would sincerely like to thank Professor Karl Ungersböck at Wien University for his introduction to the experimental model, Dr Klaus Frank from BGT (Überlingen/Germany) for the generous permission to use EMPHO, Monika Westenhuber for the excellent secretarial assistance, and Michael Mahlzahn, Laszlo Kopacz, and Andrea Schollmayer for the flawless technical help and support.
Received August 14, 1995; revision received January 3, 1996; accepted January 11, 1996.
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