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P-326 Effect of central thyrotropin-releasing hormone (TRH) on the hepatic microcirculation
S118
Posters / International Hepatology Communications 3 Suppl. (1995) $37-S169
P-325 s r v o Y ON RELATION BETWEEN OXYGEN TENSION IN LIVER TISSUE AND THAT IN PORTAL VEIN AFTER ISCHEMIA I REPERFUSION A.Urakami, T.Ota, R.Hirai, T.Tsukazaki, H.Matsumoto, H.Soga, &Nawa,
N.Shimizu 2rid Dept. of Surgery, Okayama, Japan Introduction : Sclnce the oxygen supply to peripheral tissue is carried out in accordance with the mass-transport law of diffusion, the measurement of oxygen tension in tissue(PtO2) is useful to know the condition of oxygen supply. So we tried to evaluate the degree of oxygen diffusion disturbance after liver ischemia / repeffusion by measraing PtO2 and that in potal vein (PpvO2) with the ratio of them(Pt/PpvO2). Methods : Using mongrel dogs fully anesthetized, a partially (70%) ischemie liver model was prepared. We used arterial oxygen tension(PaO2), PtO2, PpvO2, Pt/PpvO2 as the indicators of oxygen diffusion, and serum GOT as tissue injury ; PtO2 was measured using a mass spectrometer ( MEDSPECT - II, Chemetron, USA ). The subjects were divided into three groups : group I ( n=6 ), isehemia for 30rain.; group II ( n=8 ), ischemia for 60min.;group Ill I n=6 ), ischemia for 90rain. Result : When ventilated with room air, PaO2, PtO2, PpvO2, and Pt/PpvO2 were 92.6±20.1, 29.0--+ 12.8, 55.3_+ 10.1 mmHg, and 0.55±0.29, respectively. When ventilated with 50%02, they were 200.1 ± 36.8, 52.3 415.9, 63.6± 15.2 mmHg, and 0.86-+ 0.29. After induction of isehemia, PtO2 immediately decreased with significance, presenting a plateau pattern after 15rain. in all groups. The lowest PrO2 were 9.4±4.4, 7.4--+ 1.3 and 6.6± 2.8mmHg in groupI, II and III, respectively. After starting repeffnsion, PtO2 in grouplII was significantly lower than groupI Oa < 0.05), and also Pt/PpvO2 in groupIII was lower than groupI (P < 0.05) at each time point. There was observed a trend that Pt/PpvO2 decreased as GOT was elevated. Conclusion : It was revealed that the recovery of PtO2 and Pt/PpvO2 after starting repeffusion was depressed when the isehemic lime was prolonged, and that Pt/PpvO2 tended to decrease as serum GOT was elevated. These result suggested that the severer was the tissue injury due to ischemia / reperfusion, the stronger was the oxygen diffusion disturbance.
P-327
ROLE OF NITRIC OXIDE ON HEPATIC ARTERIAL BLOOD FLOW IN RATS WITH CCL4-INDUCED LIVER I N J U R Y N.Tanaka, K.Tanaka, M.Kondo, T.Sakaguchi, M.Morimoto, K.Numata, H.Okazaki, M.Hoshino, H.Sekihara 3rd Dept. of Medicine, Yokohama City Univ. of Medicine Yokohama, Japan (Aim) We have reported that in patients with acute viral hapafitis, the hepatic arterial blood flow i n c r e a s e d s i g n i f i c a n t l y a n d it d i d c o r r e l a t e w i t h t h e speed of recover)" from the disease (Hepatology 1993; 18; 2 1 - 2 7 ) . In t h i s s t u d y , w e e v a l u a t e d t h e e f f e c t o f CC14induced acute hapatic injury on hapatic blood flow in rats under unstrained and concious state using microsphere method and investigated the effect of N i t r i c O x i d e (NO) o n h a p a t i c b l o o d f l o w u s i n g N G - n i t r o L - a r g i n i n e (NNA). ( M e t h o d s ) Exp. 1: SD r a t s w e r e t r e a t e d w i t h a n i n j e c t i o n o f CC14 ( 5 0 0 ~ t l / k g ) i n t r a p e r i t o n e a l l y . Hemodynamic studies were performed 24 hour, 3 days a n d 7 d a y s a f t e r . Ex-p.2: T o e v a l u a t e t h e e f f e c t o f NO o n h e p a t i c b l o o d f l o w 2 4 h o u r a f t e r i n j e c t i o n o f CC14, w e performed hemodynamic studies after administration o f NNA. ( R e s u l t s ) In CC14 r a t s , h e p a t i c a r t e r i a l b l o o d flow was significantly increased and peaked at 24 hours a f t e r i n j e c t i o n , t h e n d e c l i n e d a t 3 a n d 7 d a y s b u t still r e m a i n e d h i g h c o m p a r e d t o t h a t o f c o n t r o l s . NNA treatment decreased on hepatic arterial blood flow in a dose dependant manner. High dose of NNA(10-3M) d e c r e a s e d it t o t h e l e v e l o f t h e c o n t r o l s . ( C o n c l u s i o n ) We found that in CCl4-induced acute hepatic injury r a t s , t h e h e p a t i c a r t e r i a l b l o o d f l o w i n c r e a s e d a n d NO w a s s u g g e s t e d o n e o f t h e m e c h a n i s m s o f it.
P-326 EFFECT OF C E N T R A L T H Y R O T R O P I N R E L E A S I N G H O R M O N E ( T R H ) ON T H E HEPATIC MICROCIRCULATION K. Tamori, M. Yoneda, S. Yokohama, Y. Sato, K. Nakamta-a, M, Fujita, A. Kimura, K. Baba, H. Salto, K, Akiyama and I. Makino Department of Internal Medicine II, Asahikawa Medical College, Japan Central neuropeptides plays a role in many physiological and pathophysiological regulations through autonomic nervous systems. TRH is known to be distributed in the central nervous system and act as neurotransmitter to regulate gastric functions through vagal and muscasinic pathways. Liver is also richly innervated and a role of central neuropeptide in hepatic functions is expected. However, still very little is known about central regulation of hepatic functions by neurupepfides. Purpose: To investigate the effect of central TRH on hepatic blood flow (HBF). Methods: The hepatic blood flow was me~ured by the hydrogen gasclearance technique each 15 rain period. Male Wistar rats were anesthetized with urethane, and a platinum wire type electrode was inserted into the hepatic left lateral lobe. After two measurement of basal HBF, either the stable TRH analog, RX 77368 (5, 10, 100 or 500 ng) or saline vehicle was injected intracisternally (ic) or intravenously. HBF response was observed for 90 rain after the peptide. The change of HBF was expressed as percent compared to basal HBF. Results: Intracisternal injection of TRH (10 ng) significantly enhanced HBF with peak response at 15 rain after the peptide, and the enhanced HBF was returned to basal at 60 min (Mean + SEM; %: 15 rain 134 + 5; 30 rain 133 ± 10; 45 rain 115 + 6; 60 rain 102 _+ 10; 75 rnin 112 -+ 8; 90 rain 103 + 9). This stimulator3, effect of central TRH was dose-related ranging from 5 to 100 ng. The stimulation of HBF by central TRH was abolished by atropine, indomethaein, L-NAME ~cl vagotomy. Intravenous injection of TRH d~d not have any effect on HBF. Conclusion: TRH acts in the brain to enhance HBF through vagalmuscarinic, prostaglandin and nitric oxide pathways. These results suggest the central regulation of hepatic hemodynamics by neuropepddes.
P-328
RELATIONSHIP BETWEEN HEPATIC OXYGEN METABOLISM AND HEPATIC VENOUS HEMOGLOBIN OXYGEN SATURATION AFTER HEPATECTOMY IN RATS S.Yoshioka, M.Miyazaki, H.ltoh, T.Kaiho, S.Ambiru, A.Togawa, M,Ohtsuka, K.Sasada, M.Shimizu, H.Yoshidome, H.Omoto, A.Katoh, S.Nakamura, A.Okuno, Y.Nukui, S.Nozawa, H.Yoshitomi, N.Nakajima, Y.Fukuda* I st Dept. of Surgery and 2nd Dept. of Physiology*, Chiba Univ. school of Medicine, Chiha, Japan Hepatic venous oxygen saturation (ShvO2) was measured before and after partial hepatectomy in sixteen Wistar rats. It was evaluated in the relationship to hepatic oxygen metabolism; hepatic oxygen delivery (HOD), hepatic oxygen consumption (HOC), hepatic oxygen extraction ratio (HOER). ShvO2 significantly decreased at third operative days, compared with the preoperative value.(p<0.05) There is no defference of hepatic portal and arterial blood flow between third postoperative and the preoperative value. However, HOC and HOER revealed a remarkable increase at the 3rd postoperative day (P<0.05).There was significantly close correlation between HOC and ShvO2 (r=--0.791, p<0.005, Y=-0.52X+43.78), and between HOER and ShvO2(r=-0.913, p<0.005, Y=- 1.29X+ 107.26). It was concluded that a decrease of ShvO2 after hepatectomy could reflect hepatic oxygen metabolism in a regenerating liver.
Posters / International Hepatology Communications 3 Suppl. (1995) $37-S169
P-325 s r v o Y ON RELATION BETWEEN OXYGEN TENSION IN LIVER TISSUE AND THAT IN PORTAL VEIN AFTER ISCHEMIA I REPERFUSION A.Urakami, T.Ota, R.Hirai, T.Tsukazaki, H.Matsumoto, H.Soga, &Nawa,
N.Shimizu 2rid Dept. of Surgery, Okayama, Japan Introduction : Sclnce the oxygen supply to peripheral tissue is carried out in accordance with the mass-transport law of diffusion, the measurement of oxygen tension in tissue(PtO2) is useful to know the condition of oxygen supply. So we tried to evaluate the degree of oxygen diffusion disturbance after liver ischemia / repeffusion by measraing PtO2 and that in potal vein (PpvO2) with the ratio of them(Pt/PpvO2). Methods : Using mongrel dogs fully anesthetized, a partially (70%) ischemie liver model was prepared. We used arterial oxygen tension(PaO2), PtO2, PpvO2, Pt/PpvO2 as the indicators of oxygen diffusion, and serum GOT as tissue injury ; PtO2 was measured using a mass spectrometer ( MEDSPECT - II, Chemetron, USA ). The subjects were divided into three groups : group I ( n=6 ), isehemia for 30rain.; group II ( n=8 ), ischemia for 60min.;group Ill I n=6 ), ischemia for 90rain. Result : When ventilated with room air, PaO2, PtO2, PpvO2, and Pt/PpvO2 were 92.6±20.1, 29.0--+ 12.8, 55.3_+ 10.1 mmHg, and 0.55±0.29, respectively. When ventilated with 50%02, they were 200.1 ± 36.8, 52.3 415.9, 63.6± 15.2 mmHg, and 0.86-+ 0.29. After induction of isehemia, PtO2 immediately decreased with significance, presenting a plateau pattern after 15rain. in all groups. The lowest PrO2 were 9.4±4.4, 7.4--+ 1.3 and 6.6± 2.8mmHg in groupI, II and III, respectively. After starting repeffnsion, PtO2 in grouplII was significantly lower than groupI Oa < 0.05), and also Pt/PpvO2 in groupIII was lower than groupI (P < 0.05) at each time point. There was observed a trend that Pt/PpvO2 decreased as GOT was elevated. Conclusion : It was revealed that the recovery of PtO2 and Pt/PpvO2 after starting repeffusion was depressed when the isehemic lime was prolonged, and that Pt/PpvO2 tended to decrease as serum GOT was elevated. These result suggested that the severer was the tissue injury due to ischemia / reperfusion, the stronger was the oxygen diffusion disturbance.
P-327
ROLE OF NITRIC OXIDE ON HEPATIC ARTERIAL BLOOD FLOW IN RATS WITH CCL4-INDUCED LIVER I N J U R Y N.Tanaka, K.Tanaka, M.Kondo, T.Sakaguchi, M.Morimoto, K.Numata, H.Okazaki, M.Hoshino, H.Sekihara 3rd Dept. of Medicine, Yokohama City Univ. of Medicine Yokohama, Japan (Aim) We have reported that in patients with acute viral hapafitis, the hepatic arterial blood flow i n c r e a s e d s i g n i f i c a n t l y a n d it d i d c o r r e l a t e w i t h t h e speed of recover)" from the disease (Hepatology 1993; 18; 2 1 - 2 7 ) . In t h i s s t u d y , w e e v a l u a t e d t h e e f f e c t o f CC14induced acute hapatic injury on hapatic blood flow in rats under unstrained and concious state using microsphere method and investigated the effect of N i t r i c O x i d e (NO) o n h a p a t i c b l o o d f l o w u s i n g N G - n i t r o L - a r g i n i n e (NNA). ( M e t h o d s ) Exp. 1: SD r a t s w e r e t r e a t e d w i t h a n i n j e c t i o n o f CC14 ( 5 0 0 ~ t l / k g ) i n t r a p e r i t o n e a l l y . Hemodynamic studies were performed 24 hour, 3 days a n d 7 d a y s a f t e r . Ex-p.2: T o e v a l u a t e t h e e f f e c t o f NO o n h e p a t i c b l o o d f l o w 2 4 h o u r a f t e r i n j e c t i o n o f CC14, w e performed hemodynamic studies after administration o f NNA. ( R e s u l t s ) In CC14 r a t s , h e p a t i c a r t e r i a l b l o o d flow was significantly increased and peaked at 24 hours a f t e r i n j e c t i o n , t h e n d e c l i n e d a t 3 a n d 7 d a y s b u t still r e m a i n e d h i g h c o m p a r e d t o t h a t o f c o n t r o l s . NNA treatment decreased on hepatic arterial blood flow in a dose dependant manner. High dose of NNA(10-3M) d e c r e a s e d it t o t h e l e v e l o f t h e c o n t r o l s . ( C o n c l u s i o n ) We found that in CCl4-induced acute hepatic injury r a t s , t h e h e p a t i c a r t e r i a l b l o o d f l o w i n c r e a s e d a n d NO w a s s u g g e s t e d o n e o f t h e m e c h a n i s m s o f it.
P-326 EFFECT OF C E N T R A L T H Y R O T R O P I N R E L E A S I N G H O R M O N E ( T R H ) ON T H E HEPATIC MICROCIRCULATION K. Tamori, M. Yoneda, S. Yokohama, Y. Sato, K. Nakamta-a, M, Fujita, A. Kimura, K. Baba, H. Salto, K, Akiyama and I. Makino Department of Internal Medicine II, Asahikawa Medical College, Japan Central neuropeptides plays a role in many physiological and pathophysiological regulations through autonomic nervous systems. TRH is known to be distributed in the central nervous system and act as neurotransmitter to regulate gastric functions through vagal and muscasinic pathways. Liver is also richly innervated and a role of central neuropeptide in hepatic functions is expected. However, still very little is known about central regulation of hepatic functions by neurupepfides. Purpose: To investigate the effect of central TRH on hepatic blood flow (HBF). Methods: The hepatic blood flow was me~ured by the hydrogen gasclearance technique each 15 rain period. Male Wistar rats were anesthetized with urethane, and a platinum wire type electrode was inserted into the hepatic left lateral lobe. After two measurement of basal HBF, either the stable TRH analog, RX 77368 (5, 10, 100 or 500 ng) or saline vehicle was injected intracisternally (ic) or intravenously. HBF response was observed for 90 rain after the peptide. The change of HBF was expressed as percent compared to basal HBF. Results: Intracisternal injection of TRH (10 ng) significantly enhanced HBF with peak response at 15 rain after the peptide, and the enhanced HBF was returned to basal at 60 min (Mean + SEM; %: 15 rain 134 + 5; 30 rain 133 ± 10; 45 rain 115 + 6; 60 rain 102 _+ 10; 75 rnin 112 -+ 8; 90 rain 103 + 9). This stimulator3, effect of central TRH was dose-related ranging from 5 to 100 ng. The stimulation of HBF by central TRH was abolished by atropine, indomethaein, L-NAME ~cl vagotomy. Intravenous injection of TRH d~d not have any effect on HBF. Conclusion: TRH acts in the brain to enhance HBF through vagalmuscarinic, prostaglandin and nitric oxide pathways. These results suggest the central regulation of hepatic hemodynamics by neuropepddes.
P-328
RELATIONSHIP BETWEEN HEPATIC OXYGEN METABOLISM AND HEPATIC VENOUS HEMOGLOBIN OXYGEN SATURATION AFTER HEPATECTOMY IN RATS S.Yoshioka, M.Miyazaki, H.ltoh, T.Kaiho, S.Ambiru, A.Togawa, M,Ohtsuka, K.Sasada, M.Shimizu, H.Yoshidome, H.Omoto, A.Katoh, S.Nakamura, A.Okuno, Y.Nukui, S.Nozawa, H.Yoshitomi, N.Nakajima, Y.Fukuda* I st Dept. of Surgery and 2nd Dept. of Physiology*, Chiba Univ. school of Medicine, Chiha, Japan Hepatic venous oxygen saturation (ShvO2) was measured before and after partial hepatectomy in sixteen Wistar rats. It was evaluated in the relationship to hepatic oxygen metabolism; hepatic oxygen delivery (HOD), hepatic oxygen consumption (HOC), hepatic oxygen extraction ratio (HOER). ShvO2 significantly decreased at third operative days, compared with the preoperative value.(p<0.05) There is no defference of hepatic portal and arterial blood flow between third postoperative and the preoperative value. However, HOC and HOER revealed a remarkable increase at the 3rd postoperative day (P<0.05).There was significantly close correlation between HOC and ShvO2 (r=--0.791, p<0.005, Y=-0.52X+43.78), and between HOER and ShvO2(r=-0.913, p<0.005, Y=- 1.29X+ 107.26). It was concluded that a decrease of ShvO2 after hepatectomy could reflect hepatic oxygen metabolism in a regenerating liver.