Acta Neurochir (Wien) (1991) 113:69-73
cta h -
u r o c lrurglca
9 Springer-Verlag 1991 Printed in Austria
The Effect of Very Early Cisternal Irrigation on Basilar Artery Spasm After SAH in the Rat Model
I. H. Aydin and A. Onder
Department of Neurosurgery, Atatfirk University Medical School, Erzurum, Tfirkiye
Summary
The authors have investigated the effect of very early irrigation of the cerebrospinal fluid (CSF) space in the haemorrhage rat model of vasospasm. Fifteen rats had basilar cistern irrigation with phys- iological saline for 3 hours after subarachnoid haemorrhage (SAH), and fifteen control rats had subarachnoid haemorrhage without ir- rigation of clot.
The changes in basilar arteries diameters were determined by angiograms obtained from the rats. The post haemorrhage anglo- grams showed significant basilar artery spasm in both groups (P ~< 0.0005, t-test). However in the last angiogram the basilar artery diameter was found to have the same value measured before sub- arachnoid haemorrhage in the irrigation group whereas no obvious change was observed in the control group. In the irrigation group the mean diameter of the basilar artery in the last angiogram was 0.412ram. (0.30ram to 0.50mm). None of the animals, treated by cisternal irrigation, showed angiographic vasospasm while the latter group did (P ~< 0.0005). Animals treated with physiological saline irrigation had a median clot grade of 0.40 (range grade 0 to 2);
control rats had a median grade 2.86 (range grade 1 to 4, P < 0.001, Mann-Withney U test), on the brain stem, indicating significant reduction of clot by lavage.
In conclusion, performance of experimental physiological saline irrigation at a very early time after subarachnoid haemorrhage pre- vents the arteriographic and morphological changes of both acute
and
late vasospasms.Keywords: Cerebral vasospasm; subarachnoid haemorrhage; cis- ternal irrigation; rat.
Introduction
T h e clear-cut r e l a t i o n s h i p b e t w e e n the a m o u n t o f b l o o d i n the b a s a l cisterns a n d the i n c i d e n c e a n d se- verity o f arterial s p a s m has b e e n d e m o n s t r a t e d by clin- i c o - r a d i o l o g i c a l studies u s i n g d a t a f r o m c o m p u t e d t o m o g r a p h i c (CT) e x a m i n a t i o n s as well as by recent
experimental investigations
2, 7, 15, 20, 21, 22These f i n d i n g s have
led
to e n d e a v o u r s to r e m o v e the b l o o d f r o m the cerebral cisterns a r o u n d the vesselsin o r d e r to i n h i b i t the a c c u m u l a t i o n o f high c o n c e n - t r a t i o n s o f s p a s m o g e n i c agents p r o d u c e d by b l o o d clot lysis, There is general a g r e e m e n t a b o u t the fact t h a t p o s t - h a e m o r r h a g i c clot lysis w i t h i n the s u b a r a c h n o i d space with c o n s e q u e n t release o f s p a s m o g e n i c m e t a b - olites, derived f r o m b r e a k d o w n p r o d u c t s o f b l o o d , plays a p i v o t a l role i n the d e v e l o p m e n t o f cerebral
vasospasm 4,
5, 8, 9, 10, 21, 22, 27It was o u r a s s u m p t i o n t h a t cisternal i r r i g a t i o n with saline at a very early p e r i o d after h a e m o r r h a g e w o u l d be a suitable m o d e o f s p a s m p r e v e n t i o n a n d t r e a t m e n t . T h e f o l l o w i n g e x p e r i m e n t s were p e r f o r m e d i n
order
to e x a m i n e the efficacy o f very early cisternal i r r i g a t i o n to p r e v e n t the d e v e l o p m e n t o f a n g i o g r a p h i c vessel n a r - r o w i n g i n a r a t m o d e l o f cerebral v a s o s p a s m .
Material and Method
In this study, 30 ZBZ Cara rats were used, each weighing ap- proximately 350 grams. The rats were anaesthetized by an intra- muscular injection of 0.1-0.2 ml/100 gr of Innovar-Vet (Cilag AG Schaffhausen-Switzerland) containing 0.4rag Fentanyl and 20mg Droperidol per miligram and anaesthetization was continued by giving very small dozes. The animals were laid down in supine po- sition on a standard rat operation board and fixed by the tails, legs, and teeth.
The abdomen was opened by vertical incision. The aorta was dissected under the operating microscope and catheterized distal to the renal artery origin. The catheter was pushed towards the level of the arch of the aorta. The panangiography was performed by injecting 1-2 ml of Urographine of 60% (Sehering AG Berlin Berg- kamen, W. Germany) through catheter. With the completion of this process, the rats were turned into prone position and their heads were slightly flexed downwards. Following the microsurgical dis- section of the atlanto-occipital membrane, the cisterna magna was punctured and 0.1 ml CSF was withdrawn. After withdrawal of au- tologous arterial blood from the aortic catheter, CSF and nonhe- parinized blood were mixed to prevent premature clotting and 0.1 ml
70 I . H . Aydin and A. Onder: The Effect of Very Early Cisternal Irrigation of Basilar Artery Spasm After SAH in the Rat Models
of the mixture was injected over a period of one minute into the cisterna magna. After blood injection, the operation table was tilted 30 ~ down to promote the distribution of blood within the basal cisterns.
After about ten minutes, a second panangiography was per- formed to demonstrate basilar and vertebral arteries. Then 15 rats were spared to evaluate the effects of cisternal irrigation and another 15 used for control.
The animals in the cisternal irrigation group were treated by a cisternal lavage 3 hours later by withdrawing 0.1 ml of CSF and injecting 0.1 ml physiological saline. This fluid exchange was repeated several times at intervals of 15-30 minutes until the CSF was clear.
A third angiogram was taken to observe especially the basilar artery diameter when the CSF was clear enough to demonstrate no blood elements.
Following the third angiography all the animals were sacrified and their brains were taken out for morphological evaluation.
Examinations of the changes in the angiographic diameter of the basilar artery were made using a Zeiss stereo microscope with 10- fold magnification. The diameter of the basilar artery was measured at three corresponding locations along the course of the vessel. Sta- tistical evaluation of the changes in the angiographic diameter of the basilar artery was performed using student's t test.
The amount of clot present in brains was graded on a scale of 0 to 4 according to the method described by Alexander
etal. 1,
and statistically evaluated by Mann-Withney U test.The animals with respiratory dysfunction and those which did not survive for different reasons were discarded and replaced by new ones. Only four of them had tracheotomy during the study.
R e s u l t s
Angiography
I n b o t h g r o u p s , f o l l o w i n g t h e c i s t e r n a l b l o o d i n j e c - t i o n , i t w a s o b s e r v e d t h a t t h e b a s i l a r a r t e r y d i a m e t e r w a s r e m a r k a b l y n a r r o w e d . T h e p a i r e d s t u d e n t ' s t t e s t b e t w e e n f i r s t t w o a n g i o g r a m s o f c i s t e r n a l i r r i g a t i o n a n d c o n t r o l g r o u p s g a v e v a l u e o f t = 7 . 9 5 3 a n d 8 . 4 5 8 re-
spectively which are statically significant (P < 0.0005) (Fig. 1).
In the third angiograms made after three hours of subarachnoidal haemorrhage, the vasospasm had clearly disappeared in the irrigation group, whereas the degree of basilar artery spasm was increased in the control group (P ~< 0.0005) (Fig. 2). Table 1 shows the comparison of changes in the diameter of the basilar artery between cisternal irrigation and control groups.
There was a mean reduction of 0.007 mm in basilar artery diameter in rats with irrigation, compared to a 0.133 mm reduction in control rats.
Morphological Changes
The morphological changes around the ventral brain stem and cisterns of the clots present in each of
0.60-
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0.~0
.~ 0.40-
~3
o30
~, 0.20-
rg
_~ 010
u~
e~
r n
0 before after 10 after 3 before after 10 after 3 SAH minutes hours Time SAH minutes hours Cisternal irrigation group Control group Fig. 2. Graphic presentation of the changes in the diameter of basilar artery. Comparison of cisternal irrigation and control groups.
Changes of the vessel diameter in the control group are statistically significant (P < 0.0005)
Fig. 1. Angiographic presentation of basilar arteries in irrigation
(right) and control group (left) Fig. 3. Postmortem brain specimens in control group
I. H. Aydin and A. Onder: The Effect of Very Early Cisternal Irrigation on Basilar Artery Spasm After SAH in the Rat Model
Table 1. The Comparison of Changes in the Diameter of the Basilar Artery Between Cisternal Irrigation and Control Groups
71
Cisternal irrigation group Control group
Pat. number Diameter of basilar artery
before after 10 after 3 difference: before after 10 after 3 difference:
SAH minutes hours before SAH SAH minutes hours before SAH
to after to after
3 hours 3 hours
A1 A2 A3 B1 B2 B3
1 0.44 0.32 0.42 - 0.02 0.41 0.37 0.35 0.06
2 0.37 0.28 0.38 + 0.01 0.40 0.35 0.30 0. I0
3 0.35 0.32 0.34 - 0.01 0.44 0.40 0.25 0. I9
4 0.52 0.35 0.50 - 0.02 0.48 0.40 0.30 O. t 8
5 0.34 0.28 0.33 - 0.01 0.51 0.42 0.32 O. 19
6 0.42 0.35 0.44 + 0.02 0.50 0.43 0.34 0.16
7 0.44 0.30 0.44 0.00 0.44 0.35 0.34 O. 10
8 0.50 0.28 0.49 - 0.01 0.47 0.41 0.28 O. 19
9 0.48 0.35 0.48 0.00 0.38 0.32 0.29 0.09
10 0.40 0.34 0.41 + 0.01 0.30 0.30 0.18 0.12
11 0.43 0.35 0.42 - 0.01 0.43 0.35 0.29 0.14
12 0.39 0.30 0.38 - 0.01 0.45 0.40 0.28 0.17
13 0.32 0.25 0.30 - 0.02 0.46 0.41 0.35 0.11
14 0.38 0.30 0.37 - 0.01 0.41 0.38 0.34 0.07
15 0.51 0.35 0.48 -0.03 0.37 0.34 0.25 0.12
Mean 0.419 0.315 0.412 0.007 0.430 0.375 0.297 0.133
The paired student's t test between A 1 and B 1 gave a value of t = 0.497 and had P 0.375. On the other hand the difference between A 3 and B 3 is very significant. (t = 5.749, P < 0.0005).
t h e c o n t r o l a n d c i s t e r n a l i r r i g a t i o n g r o u p s a r e s h o w n in T a b l e 2. I n t h e c o n t r o l g r o u p , p o s t m o r t e m i n s p e c t i o n o f t h e b r a i n s t e m u n d e r t h e o p e r a t i n g m i c r o s c o p e m a g - n i f i c a t i o n , c i s t e r n s a n d b a s i l a r a r t e r y r e v e a l e d in all
rats, b l o o d c l o t s filling t h e c i s t e r n a m a g n a w i t h b l o c k - a g e o f t h e f o u r t h v e n t r i c l e . T h e b a s i l a r a r t e r y w a s e m b e d d e d in t h i c k s u b a r a c h n o i d b l o o d c o l l e c t i o n s o f d i f f e r e n t g r a d e s w h i c h c o u l d be r e m o v e d b y m i c r o s u r - g i c a l d i s s e c t i o n (Fig. 3). I n c o n t r a s t , in t h e c i s t e r n a l i r r i g a t i o n g r o u p , n o r e l e v a n t s u b a r a c h n o i d c l o t c o l l e c - t i o n s e i t h e r w i t h i n t h e c i s t e r n a m a g n a o r a l o n g t h e c o u r s e o f b a s i l a r a r t e r y c o u l d b e d e t e c t e d ( M a n n - W i t h - n e y U test, u = 2, z -- -4.583, P < 0.001) (Fig. 4).
Fig. 4. Postmortem brain specimens in cisternal irrigation group
Discussion
T h e w e l l - f o u n d e d c o r r e l a t i o n b e t w e e n t h e p r e s e n c e a n d a m o u n t o f c l o t in t h e s u b a r a c h n o i d c i s t e r n s a n d t h e o c c u r e n c e o f v a s o s p a s m as w e l l as t h e c o n s e q u e n t s u g g e s t i o n t h a t c o m p o n e n t s o f b l o o d a r e r e s p o n s i b l e f o r t h e i n d u c t i o n o f v a s o s p a s m h a v e led t o e x t e n s i v e e f f o r t s e i t h e r b y s u r g i c a l a n d / o r p h a r m a c o l o g i c a l m e a n s t o e v a c u a t e t h e s u b a r a c h n o i d c l o t f r o m b a s a l c i s t e r n s in o r d e r to p r e v e n t t h e d e v e l o p m e n t o f is- c h a e m i c d e f i c i t s i, 18, 20, 21, 22, 24, 3o
I t w a s o n l y w i t h t h e i n c r e a s i n g use o f e a r l y o p e r a t i v e i n t e r v e n t i o n f o r c e r e b r a l a n e u r y s m c l i p p i n g in r e c e n t
72 I . H . Aydin and A. 13nder: The Effect o f Very Early Cisternal Irrigation o f Basilar Artery Spasm After SAH in the Rat Models
Table 2. Amount of clot Present around the Brain Stem at Sacrifice
Pat. number Clot grade
cisternal irrigation group control group
1 0 2
2 0 2
3 0 3
4 1 3
5 0 3
6 1 4
7 0 3
8 1 4
9 0 3
10 0 2
11 0 3
12 I 3
13 0 3
14 2 2
15 0 3
Mean 0.40 2.86
Grading scale system (1).
Grade 0: Total absence o f clot.
Grade 1: Trace amount o f clot present.
Grade 2: Minimal clot present (that is, two to six areas o f clot, no more than 2 to 4 mm across, randomly distributed over the ventral brain stem without predilection for the basilar artery).
Grade 3: Moderate clot present (that is, more and/or larger areas o f clot, with greater involvement o f the basilar artery).
Grade 4: Brain stem and basilar artery essentially encased in clot.
Mann-Withney U test is used for comparison o f two groups, and a very significant difference was found (u = 2, z = -4.583, P < 0.00 I).
years that the idea of aggressive intra-operative surgical lavage of cisterns was reinstituted and a concept of
"Scavenger Surgery" was proposed 6, 11, 12, 23
Experimental studies substantiated the fact that wash out of blood clots was supposed to be effective only when performed within a time limit of 48 hours after aneurysm rupture 5, 16. Despite the fact that, in a number of clinical studies the efficacy of cisternal ir- rigation to prevent the development of vasospasm at least during early cerebral aneurysm surgery could be demonstrated 3, 6,
14, 15, 19, 25the blood clots around cerebral vessels at the base of brain are sometimes so adherant that clot removal is not possible 17, 20, 21, 22 However, Alexander
e t a l .reported that this clot re- moval had no significant effect on the neuroradiol- ogical course or degree of angiographie spasm on day 8 1. Similarly, almost all of the morphological changes associated with chronic vasospasm in both autopsy and
experimental reports were uneffected by delayed lavage 13, 1~. On the other hand, Alexander
et al.reported that cisternal lavage 24 hours after haemorrhage has no effect on the angiographic vasospasm in spite of evi- dence of clot removal as seen at sacrifice I
The acute spasm is maximal at ten minutes and the late spasm is maxim.al at two days after subarachnoid haemorrhage. The time course Of spasm is shorter in the rat as compared to other species 24. Wilkins and Levitt did not see an acute phase in their canine blood injection model 29. Also the acute phase does not seem to occur in humans 26, 28. However, the longer the period after the haemorrhage is, the more unsatisfactory will be the wash out of the clot around the basilar cistern and basilar artery and its branches. Additionally, the important perforating arteries may be damaged. The most effective metabolites in vasospasm pathogenesis are produced by blood clot lysis. Such events may occur one after another following the bleeding, but with very early cisternal irrigation, such undesirable conditions may be prevented at the very beginning, and the blood elements around arteries and cisterns may be cleaned easily before clotting. We found that vasospasm had largely disappeared, when cisternal irrigation was ini- tiated within 15 minutes and continued until clear CSF was obtained and that no blood clot elements were observed either in the basal cisterns or around the ar- teries in the postmortem inspection. But in the control group, the arterial spasm continued or the basilar artery grew more spastic (Mean difference = 0.133,
t= 5.749, P < 0.0005), and the basal cisterns were largely covered with blood clot (u = 2, z = 4.583, P < 0.001). The gen- eral constriction ratio was 0,0167 in the irrigation group while it is 0,309 in the control group.
Although it has been stated that, the reduction of gross clot after lavage was associated with decreased endothelial desquamation and platelet adherence, with a trend toward reduced intimal fibroplasia, the relative roles of gross clot and adventitial blood cells in the genesis of vasospasm were not clear
I6, 26The present study shows that complete evacuation of blood clot at 3 hours after haemorrhage is very effective in pre- venting vasospasm in the rat model.
In conclusion, we can say that the clots which are
presumably the source of vasoactive substances, can
easily be cleaned before getting more sticky by em-
ploying cisternal irrigation in the very early period of
experimental subarachnoid haemorrhage. It should
also be possible to avoid acute vasospasms and so to
prevent the development of ischaemic deficits.
I. H. Aydin and A. Onder: The Effect of Very Early Cisternal Irrigation on Basilar Artery Spasm After SAH in the Rat Model 73
Acknowledgement
The authors gratefully acknowledge Dr. Ruhi Esengun for re- viewing the manuscript and Dr. Fatin Sezgin for analysing the sta- tistical data.
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Correspondence and Reprints: Ismail HaXki Aydin, M. D., P.
K. 299, Erzurum 25000, Ttirkiye.
