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Variceal pressure, measured at endoscopy, but not portal pressure correlates with the risk of bleeding from oesophageal varices in cirrhosis
237 D I S T R I B U T I O N
A N D R E G U L A T I O N OF I S O E N Z Y M E S OF ~ A L A T E D E H Y D R O G E N A S E (NAD) IN T H E M O U S E L I V E R A C I N U S ~ H . R i e d e r t P.J. S t o w a r d . I. Dept. of M e d i c i n e , U n i v e r s i t y of M a i n z , G e r m a n y a n d +Dept. of A n a t o m y , Univ. of D u n d e e , S c o t l a n d . In h e p a t o c y t e s ~ n e r e are at l e a s t two f o r m s of N A D - l i n k e d m a l a t e d e h y d r o ~enase a mltochondrial (mMDH) and a c y t o p l a s m i c or s o l u b l e e n z y m e ( s M D H ) . A c c o r d i ~ g to the c o n c e p t of m e t a b o l i c z o n a t i o n of the l i v e r p a r e n c h y m a the distinct metabolic f u n c t i o n s of t h e s e e n z y m e s s h o u l d r e s u l t in a d i f f e r e n t localization and regulation. To v a r i f y this h y p o t h e s i s m M D H was l o c a l i z e d selectively by immunohistochemistry using a PAP-technique, and the a c t i v i t y of both e n z y m e s t o g e t h e r was v i s u a l i z e d by e n z y m e h i s t o c h e m i c a l means. Reactions were e v a l u a t e d in the p e r i p o r t a l (pp) and p e r i v e n o u s (pv) z o n e s by m i c r o p h o t o m e t r y . A d u l t a n i m a l s of e i t h e r sex s h o w e d a b o u t 2.5 t i m e s as m u c h s t a i ning i n t e n s i t y in the pp t h a n in the p v zone. In f a s t i n g (up to 64 h) m a l e mice the o v e r a l l r e a c t i o n i n t e n s i t y i n c r e a s e d a b o u t 50%, w h i l e the g r a d i e n t remained almost unchanged. The t o t a l M D H a c t i v i t y was h o m o g e n e o u s l y distributed in the l i v e r p a r e n c h y m a of n o r m a l l y fed a n i m a l s b u t d r o p p e d by a b o u t 30% in the p v z o n e in m a l e s f a s t e d f o r 16 h. P r o l o n g e d f a s t i n g r e s u l t e d in a s t e a d y i n c r e a s e of the pp a c t i v i t y , w h i l e the p v a c t i v i t y s l o w l y r e t u r n e d to the p r e f a s t i n g level. As u n d e r the e n z y m e h i s t o c h e m i c a l a s s a y c o n d i t i o n s both enzymes contribute a b o u t e q u a l l y to the m e a s u r e d a c t i v i t y , it c a n be c o n c l u ded t h a t the s M D H is a b o u t twice as a c t i v e in the pv z o n e and its a c t i v i t y d e c r e a s e s d u r i n g f a s t i n g by 50% and 6 5 % in the p v and pp zone, r e s p e c t i v e l y . In c o n j u n c t i o n w i t h the m a l i c e n z y m e sMDH has a r o l e in l i p o g e n e s i s , therefore the b e h a v i o u r of t h e s e two i s o e n z y m e s is a f u r t h e r p r o o f of the v a l i d i ty of the m e t a b o l i c zonation: with a predominantly gluconeogenic pp z o n e rich in m i t o c h o n d r i a and m M D H w h i c h a c t i v i t y i n c r e a s e s d u r i n g f a s t i n g and a predominantly l i p o g e n i c p v zone r i c h in sMDH s h o w i n g the o p p o s i t e b e h a v i o u r .
238 VARICEAL PRESSURE, MEASURED AT ENDOSCOPY, BUT NOT PORTAL PRESSURE CORRELATES WITH THE RISK OF BLEEDING FROM OESOPHAGEAL VARICES IN CIRRHOSIS. J. Rigau, J. Bosch, J.g. Bordas, R. Mastai, J. Bruix, D. Kravetz and J. Rod,s Liver Unit. Hospital Clfnico y Provincial. University of Barcelona. Spain It has been recently suggested that pressure in oesophageal varices can be safely measured at endoscopy using a pressure gauge attached to the distal end of a fiberscope. This study was aimed to evaluate this technique, and to examine the relationship between endoscopically measured variceal pressure and portal pressure, risk of variceal bleeding and endoscopic findings. Endoscopically measured pressure closely correlated with true pressure in an artificial varix system (r=0.998, n=lO0). Measurements in vivo were performed during routine endoscopy in 33 cirrhotics with oesophageal varices (20 with recent variceal bleeding). Variation of repeated measurements in 24 patients was 4.3+0.8% (M+SE). All patients had portal pressure measured as WHVP-FHVP within 24 h. Variceal pressure (12.9~0.4 mmHg) was significantly lower than portal pressure (20.5+1 mmHg, p~O.O01) and both were poorly correlated (r=0.30). Patients with varicoal bleeding had similar portal pressure than patients without bleeding (19.5+1.3 vs 21.6+1.3 mmHg, NS). However, variceal pressure was higher in patients with previous bleeding (13.9~0.5 mmHg) t h ~ in those without (11.9+0.5 mmHg, p&O.02). Variceal pressure was higher in big varices (@,6mm, 13.6+0.5 mmHg) t h ~ in small varices (~(6mm, ll.O+l.l mmHg, p(O.02) and bleeding was more frequent in patients with big varices (18/23) than in those with small varices (2/10) (p(O.O01). Tension of variceal wall, calculated as the product of pressure and radius of the varix, was much greater in bleeders than in non bleeders (60Z4 vs 35~6, p(O.O01). Our results show that contrarily to measurement of portal pressure', endoscopic measurement of variceal pressure may be helpful to define those patients with a high risk of variceal haemorrhage.
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A N D R E G U L A T I O N OF I S O E N Z Y M E S OF ~ A L A T E D E H Y D R O G E N A S E (NAD) IN T H E M O U S E L I V E R A C I N U S ~ H . R i e d e r t P.J. S t o w a r d . I. Dept. of M e d i c i n e , U n i v e r s i t y of M a i n z , G e r m a n y a n d +Dept. of A n a t o m y , Univ. of D u n d e e , S c o t l a n d . In h e p a t o c y t e s ~ n e r e are at l e a s t two f o r m s of N A D - l i n k e d m a l a t e d e h y d r o ~enase a mltochondrial (mMDH) and a c y t o p l a s m i c or s o l u b l e e n z y m e ( s M D H ) . A c c o r d i ~ g to the c o n c e p t of m e t a b o l i c z o n a t i o n of the l i v e r p a r e n c h y m a the distinct metabolic f u n c t i o n s of t h e s e e n z y m e s s h o u l d r e s u l t in a d i f f e r e n t localization and regulation. To v a r i f y this h y p o t h e s i s m M D H was l o c a l i z e d selectively by immunohistochemistry using a PAP-technique, and the a c t i v i t y of both e n z y m e s t o g e t h e r was v i s u a l i z e d by e n z y m e h i s t o c h e m i c a l means. Reactions were e v a l u a t e d in the p e r i p o r t a l (pp) and p e r i v e n o u s (pv) z o n e s by m i c r o p h o t o m e t r y . A d u l t a n i m a l s of e i t h e r sex s h o w e d a b o u t 2.5 t i m e s as m u c h s t a i ning i n t e n s i t y in the pp t h a n in the p v zone. In f a s t i n g (up to 64 h) m a l e mice the o v e r a l l r e a c t i o n i n t e n s i t y i n c r e a s e d a b o u t 50%, w h i l e the g r a d i e n t remained almost unchanged. The t o t a l M D H a c t i v i t y was h o m o g e n e o u s l y distributed in the l i v e r p a r e n c h y m a of n o r m a l l y fed a n i m a l s b u t d r o p p e d by a b o u t 30% in the p v z o n e in m a l e s f a s t e d f o r 16 h. P r o l o n g e d f a s t i n g r e s u l t e d in a s t e a d y i n c r e a s e of the pp a c t i v i t y , w h i l e the p v a c t i v i t y s l o w l y r e t u r n e d to the p r e f a s t i n g level. As u n d e r the e n z y m e h i s t o c h e m i c a l a s s a y c o n d i t i o n s both enzymes contribute a b o u t e q u a l l y to the m e a s u r e d a c t i v i t y , it c a n be c o n c l u ded t h a t the s M D H is a b o u t twice as a c t i v e in the pv z o n e and its a c t i v i t y d e c r e a s e s d u r i n g f a s t i n g by 50% and 6 5 % in the p v and pp zone, r e s p e c t i v e l y . In c o n j u n c t i o n w i t h the m a l i c e n z y m e sMDH has a r o l e in l i p o g e n e s i s , therefore the b e h a v i o u r of t h e s e two i s o e n z y m e s is a f u r t h e r p r o o f of the v a l i d i ty of the m e t a b o l i c zonation: with a predominantly gluconeogenic pp z o n e rich in m i t o c h o n d r i a and m M D H w h i c h a c t i v i t y i n c r e a s e s d u r i n g f a s t i n g and a predominantly l i p o g e n i c p v zone r i c h in sMDH s h o w i n g the o p p o s i t e b e h a v i o u r .
238 VARICEAL PRESSURE, MEASURED AT ENDOSCOPY, BUT NOT PORTAL PRESSURE CORRELATES WITH THE RISK OF BLEEDING FROM OESOPHAGEAL VARICES IN CIRRHOSIS. J. Rigau, J. Bosch, J.g. Bordas, R. Mastai, J. Bruix, D. Kravetz and J. Rod,s Liver Unit. Hospital Clfnico y Provincial. University of Barcelona. Spain It has been recently suggested that pressure in oesophageal varices can be safely measured at endoscopy using a pressure gauge attached to the distal end of a fiberscope. This study was aimed to evaluate this technique, and to examine the relationship between endoscopically measured variceal pressure and portal pressure, risk of variceal bleeding and endoscopic findings. Endoscopically measured pressure closely correlated with true pressure in an artificial varix system (r=0.998, n=lO0). Measurements in vivo were performed during routine endoscopy in 33 cirrhotics with oesophageal varices (20 with recent variceal bleeding). Variation of repeated measurements in 24 patients was 4.3+0.8% (M+SE). All patients had portal pressure measured as WHVP-FHVP within 24 h. Variceal pressure (12.9~0.4 mmHg) was significantly lower than portal pressure (20.5+1 mmHg, p~O.O01) and both were poorly correlated (r=0.30). Patients with varicoal bleeding had similar portal pressure than patients without bleeding (19.5+1.3 vs 21.6+1.3 mmHg, NS). However, variceal pressure was higher in patients with previous bleeding (13.9~0.5 mmHg) t h ~ in those without (11.9+0.5 mmHg, p&O.02). Variceal pressure was higher in big varices (@,6mm, 13.6+0.5 mmHg) t h ~ in small varices (~(6mm, ll.O+l.l mmHg, p(O.02) and bleeding was more frequent in patients with big varices (18/23) than in those with small varices (2/10) (p(O.O01). Tension of variceal wall, calculated as the product of pressure and radius of the varix, was much greater in bleeders than in non bleeders (60Z4 vs 35~6, p(O.O01). Our results show that contrarily to measurement of portal pressure', endoscopic measurement of variceal pressure may be helpful to define those patients with a high risk of variceal haemorrhage.
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