- Email: [email protected]
Hypertonic glucose infusion causes splanchnic hyperemia in patients with cirrhosis
101
HYPERTONIC CIRRHOSIS
GLUCOSE
INFUSION
CAUSES
SPLANCHNIC
HYPEREMIA
IN
PATIENTS
WITH
D. Pu~liese~ S.S. Lee, A. Koshy, R. Cerini, Y. Ozier, D. Lebrec INSERM U24, HSpital Beaujon, Clichy, France
Ingestion of glucose, similar to other dietary constituents, is known to induce splanchnic hyperemia both in man and in animals. Many mechanisms, involving intestinal motility and absorption, have been proposed to explain this vascular reaction, but none are completely satisfactory. This study was designed to evaluate if hyperglycemia itself could induce hemodynamic changes. Seven patients with alcoholic cirrhosis were studied before and 30 min after 15% glucose infusion at 2 ml/min. There was no significant change in cardiac output, mean arterial pressure, systemic vascular resistance and serum osmolality. Results of other measurements are given below (meantSD): Measurement
Basal
Hepatic venous pressure gradient Hepatic blood flow (I/min) Azygos blood flow (i/min) Leg blood flow (ml/min.100 ml) Blood glucose (mmol/l)
(mmHg)
18.0±3.3 1.17±0.3 0.46±0.8 3.92±1.9 4.88±0.3
i.v. glucose 20.4±3.7 1.49±0.6 0.56±1.7 3.07±1.7 7.53±0.9
P <0.005 ns <0.05 <0.05 <0.001
In conclusion, marked increases in portal pressure and in azygos blood flow associated with lack of major changes in systemic hemodynamics suggest the occurrence of a selective splanchnic vascular reaction similar to postprandial hyperemia, but independent of intestinal mucosal exposure to glucose. Furthermore, caution is advised in the use of i.v. hypertonic glucose in patients with variceal bleeding since it increases splanchnic blood flow.
102
ALPHA-AND GAMMA-INTERFERON (IFN) BUT NOT INTERLEUKIN-1 (IL-I) INCREASE SYNTHESIS AND SECRETION OF 62-MICROGLOBULIN (B2-M) BY HEPATOCYTES. Ramadori,G.,
Mitsch,A.,
Rieder,H.,
Dippold,W.,
Meyer zum BOschenfelde,K.-H.
I. Med.Klinik und Poliklinik der Johannes Gutenberg-Universit~t Mainz, FRG. Increased B2-M serum levels have been measured in patients with viral infections, malignancies and rejection reaction after renal or cardiac transplantation. Interferon therapy also induces an increase of B~-M plasma levels. However the site of synthesis of serum B 2M is still unknown. We studied B2-M synthesis by 2 human hepatoma cell lines (Mz-Hep-1 and PLC/PRF 5) as well as by murzne hepatocyte primary cultures. Cells were pulsed (60') with medium containing 35S-methionin and then chased for different periods of time with medium containing an excess of cold methionine. 6~-M was immunoprecipitated from radiolabeled lysates and media, immunoprecipitates were @nalysed by SDS-PAGE. To study the effect of alpha- and gamma-IFN as well as of IL-1 cells were incubated with the lymphokines for 20 hours and then pulsed for 2 hours with 35S-methionine containing medium. The effect of the lymphokine was studied at the RNA-level by Northern Blot-analysis. Human hepatoma cells as well as murine hepatocytes synthesize and secrete Bp-M. Both IFN induce a dose and time dependent, reversible increase of B2-M biosynthesis-not only by ~epatoma cells, but also by hepatocytes. Since the increase was also observed at the RNA-level, IFN effect is pretranslational; it is specific since, synthesis of C3 and actin remains inchanged. Synthesis of factor B is also positively influenced by IFN. No effect of IL-I on 62-M biosynthesis was observed. We conclude that 6~-M is a true secretory protein and that-the liver could be the site of its synthesis. The increased B~-M biosynthesis after treatment of the cells with IFN could help to unterstand increased B2-M sera levels under some pathological conditions and during interferon therapy.
$53
HYPERTONIC CIRRHOSIS
GLUCOSE
INFUSION
CAUSES
SPLANCHNIC
HYPEREMIA
IN
PATIENTS
WITH
D. Pu~liese~ S.S. Lee, A. Koshy, R. Cerini, Y. Ozier, D. Lebrec INSERM U24, HSpital Beaujon, Clichy, France
Ingestion of glucose, similar to other dietary constituents, is known to induce splanchnic hyperemia both in man and in animals. Many mechanisms, involving intestinal motility and absorption, have been proposed to explain this vascular reaction, but none are completely satisfactory. This study was designed to evaluate if hyperglycemia itself could induce hemodynamic changes. Seven patients with alcoholic cirrhosis were studied before and 30 min after 15% glucose infusion at 2 ml/min. There was no significant change in cardiac output, mean arterial pressure, systemic vascular resistance and serum osmolality. Results of other measurements are given below (meantSD): Measurement
Basal
Hepatic venous pressure gradient Hepatic blood flow (I/min) Azygos blood flow (i/min) Leg blood flow (ml/min.100 ml) Blood glucose (mmol/l)
(mmHg)
18.0±3.3 1.17±0.3 0.46±0.8 3.92±1.9 4.88±0.3
i.v. glucose 20.4±3.7 1.49±0.6 0.56±1.7 3.07±1.7 7.53±0.9
P <0.005 ns <0.05 <0.05 <0.001
In conclusion, marked increases in portal pressure and in azygos blood flow associated with lack of major changes in systemic hemodynamics suggest the occurrence of a selective splanchnic vascular reaction similar to postprandial hyperemia, but independent of intestinal mucosal exposure to glucose. Furthermore, caution is advised in the use of i.v. hypertonic glucose in patients with variceal bleeding since it increases splanchnic blood flow.
102
ALPHA-AND GAMMA-INTERFERON (IFN) BUT NOT INTERLEUKIN-1 (IL-I) INCREASE SYNTHESIS AND SECRETION OF 62-MICROGLOBULIN (B2-M) BY HEPATOCYTES. Ramadori,G.,
Mitsch,A.,
Rieder,H.,
Dippold,W.,
Meyer zum BOschenfelde,K.-H.
I. Med.Klinik und Poliklinik der Johannes Gutenberg-Universit~t Mainz, FRG. Increased B2-M serum levels have been measured in patients with viral infections, malignancies and rejection reaction after renal or cardiac transplantation. Interferon therapy also induces an increase of B~-M plasma levels. However the site of synthesis of serum B 2M is still unknown. We studied B2-M synthesis by 2 human hepatoma cell lines (Mz-Hep-1 and PLC/PRF 5) as well as by murzne hepatocyte primary cultures. Cells were pulsed (60') with medium containing 35S-methionin and then chased for different periods of time with medium containing an excess of cold methionine. 6~-M was immunoprecipitated from radiolabeled lysates and media, immunoprecipitates were @nalysed by SDS-PAGE. To study the effect of alpha- and gamma-IFN as well as of IL-1 cells were incubated with the lymphokines for 20 hours and then pulsed for 2 hours with 35S-methionine containing medium. The effect of the lymphokine was studied at the RNA-level by Northern Blot-analysis. Human hepatoma cells as well as murine hepatocytes synthesize and secrete Bp-M. Both IFN induce a dose and time dependent, reversible increase of B2-M biosynthesis-not only by ~epatoma cells, but also by hepatocytes. Since the increase was also observed at the RNA-level, IFN effect is pretranslational; it is specific since, synthesis of C3 and actin remains inchanged. Synthesis of factor B is also positively influenced by IFN. No effect of IL-I on 62-M biosynthesis was observed. We conclude that 6~-M is a true secretory protein and that-the liver could be the site of its synthesis. The increased B~-M biosynthesis after treatment of the cells with IFN could help to unterstand increased B2-M sera levels under some pathological conditions and during interferon therapy.
$53