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The role of nitric oxide in the regulatioatic microcirculation in a rat model of hepatic steatosis
40
Poster Sessions
chemia and reperfusion similar to shams. The secretion of conjugated bile acids reduced following I/R in controls. NAC administration was associated with significantly increased levels at 2hrs (146.3&43.7 vs 81.3~t.51.9 in controls, PiO.05) and 7hrs (97.2&45.5 vs 58.1~t45.5 in controls). It also maintained cholesterol excretion which exhibited a similar biphasic pattern in controls and acetate which dropped continuously in controls (P
I
115
THE HAEMODYNAMIC SMALL-FOR-SIZE
IMPACT OF PORTAL OVERFLOW
IN A
LIVER PIG-MODEL
C. Hillert’,
L. Mueller’, K. Helmke2, A. Koops3, C. Wilms’, A. Paetz’, K. Schroeder’, W. Notarp’, G. Krupski3, D. C. Broering’, X. Rogiers’. ‘Hepatobiliary Surgery; 2Pediatn’c Radiology; ‘Radiology, University Hospital Hamburg, Hamburg, Get-many
trations were evaluated by monitoring the changes following intravenous administration of L-arginine (300mg/kg) or L-NAME (20mg/kg). Liver enzymes AST, ALT and plasma N02/N03 levels were measured before and after L-arginine or L-NAME administration. Moderate hepatic steatosis was induced in all animals with high cholesterol diet. Total liver blood flow was significantly decreased in fatty animals as compared with controls (P
I 117
THE ROLE OF NITRIC OXIDE IN THE REGULATIOATIC
Liver dysfunction following small for size liver transplantation or extended liver resection is not only resulting from the lost of functioning liver tissue. There are several signs, that even postoperative haemodynamic changes in the reduced liver can cause cellular damage resulting in additional liver dysfunction. 24 Mini-pigs between 24 and 40 kg underwent laparotomy under general anaesthesia. Portal overflow was induced reducing the portal vein system by 75% either by complete ligation of the main portal branch to the left and the right median lobe preserving the parenchyma (LIG, n=ll) or extended resection of these segments (RES) using crash-clamp technique (n=13). Before the intervention and 1 hour and 72 hours after the operation the resistance index (RI) and flow velocity of the remaining hepatic artery and portal vein branches were measured by Doppler-Duplex Ultrasound. The microcirculation of the right lateral lobe was measured with a Laser Doppler Monitor. Animals were scarified after 72 hours collecting pathology specimens of the liver. The mortality was 0% forthe LIGand 46% (n=6) for the RES-group. 3 pigs died after technical problems intraoperatively, 3 animals died due to hepatic failure on hour 36, 48, 70. Portal pressure increased from 3,62 to 7 mm/hg in the RES-group (93%) but only from 4,45 to 6,55 in the LIG- group (46%). After resection we noticed a significant increase of the RI in the main right artery of 56% vs. 18% in the LIG-group and in the peripheral parenchyma of 39% vs. 10% (p
Hepatic steatosis is a common condition affecting about 25% of liver donors since it confers a high risk of primary non-function following liver transplantation. Impaired hepatic microcirculation in fatty liver may be associated with the poor function of the grafts. Thus this study investigated the effect of nitric oxide (NO) on hepatic microcirculation (HM) in viva in a rat model of hepatic steatosis. Spraque-Dawley rats (200.2508) were fed 2% cholesterol diet (n=12) for 12 weeks to induce hepatic steatosis or normal diet as controls (n=12). Following laparotomy, hepatic arterial and portal venous blood flow were measured using transonic flowmeter. HM was assessed using laser Doppler flowmetry and intravital fluorescent microscope (IVFM). L-arginine (300mg/kg) or L-NAME (20mg/kg) was administered intravenously and changes in hepatic haemodynamics were continuously monitored. Plasma N02/N03 was measured before and after the drug intervention. All animals feeding with 2% cholesterol diet developed moderate hepatic steatosis. The flow in HM was significantly decreased in fatty animals as compared with controls (96 & 14 vs. 178 & 12 flux unit, p
I 116
I 118
NITRIC OXIDE IS INVOLVED TISSUE
OXYGENATION
IN THE REGULATION
IN EXPERIMENTAL
OF LIVER
HEPATIC
STEATOSIS
W. Yang, A.M. Seifalian, M.C. Winslet. ‘Department Of Surgery, Royal Free And University College Medical School, University College London And Royal Free Hospital, London, UK
a,
Fatty livers are more susceptible than normal livers to &hernia-reperfusion injury occurred during liver surgery and transplantation. This study investigated the role of nitric oxide (NO) in the regulation of hepatic tissue oxygenation in an experimental model of hepatic steatosis. The steatosis was induced in Spraque-Dawley rats (200.2508) by feeding 2% cholesterol diet (n=12) or normal diet as controls (n=12). After 12 weeks, total hepatic blood flow and tissue oxygenation indicated by oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and cytochrome oxidase (Cyt Ox) were measured in viva by transonic flowmeter and near infrared spectroscopy. The effects of NO on total liver blood flow and tissue Hb, Hb02 and Cyt02 concen-
MICROCIRCULATION
IN A RAT MODEL OF HEPATIC
STEATOSIS
W. Yang, A.M. Seifalian, M.C. Winslet. ‘Department Of Surgery, Royal Free And University College Medical School, University College London And Royal Free Hospital, London, UK
S.Jaz,
LOW-DOSE
HBIG AND HIGHER-DOSE
COMBINATION
TO PREVENT
LAMIVUDINE
POST-OLT HBV RECURRENCE
Z. Karasu’,
A. Celebi’, C. Arikan3, Y. Tokat2, T. 0zacar4, M. Kilic2, T. Demirbas2, S. Acarsoy4, U.S. Akarca’, E. Galip’, F. Gunsar’, Y. Batur I. ’Gastroenterology, Ege University, I&s Turkey; 2 General Surgery, Ege University, I&s Turkey; ‘Pediatics, Ege University, I&s Turkey; 4Clinical Microbiology, Ege University, I&s Turkey
Although the efficacy of combination of lamivudine and high dose hepatitis B immune globulin (HBIG) prophylaxis to prevent recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is appreciated, it is not widely used because of high cost of HBIG. Reduction of HBIG in this combination without a decrease in efficacy should be tried. Methods: 76 HBsAg positive liver transplant recipients were included into the study. At the time of transplantation, 15 of these patients were HBV DNA positive, 10 were HBV DNA negative with lamivudine treatment, 20 patients had HDV coinfection. In all patients, in the anhepatic phase, 4000
Poster Sessions
chemia and reperfusion similar to shams. The secretion of conjugated bile acids reduced following I/R in controls. NAC administration was associated with significantly increased levels at 2hrs (146.3&43.7 vs 81.3~t.51.9 in controls, PiO.05) and 7hrs (97.2&45.5 vs 58.1~t45.5 in controls). It also maintained cholesterol excretion which exhibited a similar biphasic pattern in controls and acetate which dropped continuously in controls (P
I
115
THE HAEMODYNAMIC SMALL-FOR-SIZE
IMPACT OF PORTAL OVERFLOW
IN A
LIVER PIG-MODEL
C. Hillert’,
L. Mueller’, K. Helmke2, A. Koops3, C. Wilms’, A. Paetz’, K. Schroeder’, W. Notarp’, G. Krupski3, D. C. Broering’, X. Rogiers’. ‘Hepatobiliary Surgery; 2Pediatn’c Radiology; ‘Radiology, University Hospital Hamburg, Hamburg, Get-many
trations were evaluated by monitoring the changes following intravenous administration of L-arginine (300mg/kg) or L-NAME (20mg/kg). Liver enzymes AST, ALT and plasma N02/N03 levels were measured before and after L-arginine or L-NAME administration. Moderate hepatic steatosis was induced in all animals with high cholesterol diet. Total liver blood flow was significantly decreased in fatty animals as compared with controls (P
I 117
THE ROLE OF NITRIC OXIDE IN THE REGULATIOATIC
Liver dysfunction following small for size liver transplantation or extended liver resection is not only resulting from the lost of functioning liver tissue. There are several signs, that even postoperative haemodynamic changes in the reduced liver can cause cellular damage resulting in additional liver dysfunction. 24 Mini-pigs between 24 and 40 kg underwent laparotomy under general anaesthesia. Portal overflow was induced reducing the portal vein system by 75% either by complete ligation of the main portal branch to the left and the right median lobe preserving the parenchyma (LIG, n=ll) or extended resection of these segments (RES) using crash-clamp technique (n=13). Before the intervention and 1 hour and 72 hours after the operation the resistance index (RI) and flow velocity of the remaining hepatic artery and portal vein branches were measured by Doppler-Duplex Ultrasound. The microcirculation of the right lateral lobe was measured with a Laser Doppler Monitor. Animals were scarified after 72 hours collecting pathology specimens of the liver. The mortality was 0% forthe LIGand 46% (n=6) for the RES-group. 3 pigs died after technical problems intraoperatively, 3 animals died due to hepatic failure on hour 36, 48, 70. Portal pressure increased from 3,62 to 7 mm/hg in the RES-group (93%) but only from 4,45 to 6,55 in the LIG- group (46%). After resection we noticed a significant increase of the RI in the main right artery of 56% vs. 18% in the LIG-group and in the peripheral parenchyma of 39% vs. 10% (p
Hepatic steatosis is a common condition affecting about 25% of liver donors since it confers a high risk of primary non-function following liver transplantation. Impaired hepatic microcirculation in fatty liver may be associated with the poor function of the grafts. Thus this study investigated the effect of nitric oxide (NO) on hepatic microcirculation (HM) in viva in a rat model of hepatic steatosis. Spraque-Dawley rats (200.2508) were fed 2% cholesterol diet (n=12) for 12 weeks to induce hepatic steatosis or normal diet as controls (n=12). Following laparotomy, hepatic arterial and portal venous blood flow were measured using transonic flowmeter. HM was assessed using laser Doppler flowmetry and intravital fluorescent microscope (IVFM). L-arginine (300mg/kg) or L-NAME (20mg/kg) was administered intravenously and changes in hepatic haemodynamics were continuously monitored. Plasma N02/N03 was measured before and after the drug intervention. All animals feeding with 2% cholesterol diet developed moderate hepatic steatosis. The flow in HM was significantly decreased in fatty animals as compared with controls (96 & 14 vs. 178 & 12 flux unit, p
I 116
I 118
NITRIC OXIDE IS INVOLVED TISSUE
OXYGENATION
IN THE REGULATION
IN EXPERIMENTAL
OF LIVER
HEPATIC
STEATOSIS
W. Yang, A.M. Seifalian, M.C. Winslet. ‘Department Of Surgery, Royal Free And University College Medical School, University College London And Royal Free Hospital, London, UK
a,
Fatty livers are more susceptible than normal livers to &hernia-reperfusion injury occurred during liver surgery and transplantation. This study investigated the role of nitric oxide (NO) in the regulation of hepatic tissue oxygenation in an experimental model of hepatic steatosis. The steatosis was induced in Spraque-Dawley rats (200.2508) by feeding 2% cholesterol diet (n=12) or normal diet as controls (n=12). After 12 weeks, total hepatic blood flow and tissue oxygenation indicated by oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and cytochrome oxidase (Cyt Ox) were measured in viva by transonic flowmeter and near infrared spectroscopy. The effects of NO on total liver blood flow and tissue Hb, Hb02 and Cyt02 concen-
MICROCIRCULATION
IN A RAT MODEL OF HEPATIC
STEATOSIS
W. Yang, A.M. Seifalian, M.C. Winslet. ‘Department Of Surgery, Royal Free And University College Medical School, University College London And Royal Free Hospital, London, UK
S.Jaz,
LOW-DOSE
HBIG AND HIGHER-DOSE
COMBINATION
TO PREVENT
LAMIVUDINE
POST-OLT HBV RECURRENCE
Z. Karasu’,
A. Celebi’, C. Arikan3, Y. Tokat2, T. 0zacar4, M. Kilic2, T. Demirbas2, S. Acarsoy4, U.S. Akarca’, E. Galip’, F. Gunsar’, Y. Batur I. ’Gastroenterology, Ege University, I&s Turkey; 2 General Surgery, Ege University, I&s Turkey; ‘Pediatics, Ege University, I&s Turkey; 4Clinical Microbiology, Ege University, I&s Turkey
Although the efficacy of combination of lamivudine and high dose hepatitis B immune globulin (HBIG) prophylaxis to prevent recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is appreciated, it is not widely used because of high cost of HBIG. Reduction of HBIG in this combination without a decrease in efficacy should be tried. Methods: 76 HBsAg positive liver transplant recipients were included into the study. At the time of transplantation, 15 of these patients were HBV DNA positive, 10 were HBV DNA negative with lamivudine treatment, 20 patients had HDV coinfection. In all patients, in the anhepatic phase, 4000