- Email: [email protected]
Perisinusoidal cells in alcoholic patients with sub-normal liver histology
MECHANICAL AND ELECTROPHYSIOLOGICAL VENTRICULAR MUSCLE. 31
EFFECTS OF BILE ACIDS ON THE CARDIAC
Ofer Binah*, Arieh Bomzon** and Ori S. Better*** Rappaport Family Institute for Research in the Medical Sciences and Departments of Physiology and Biophysics* and Pharmacology**, Department of Nephrology, Rambam Medical Center*** and Faculty of Medicine, Technion, Haifa, Israel.
Depression of cardiovascular function occurs in patients with obstructive jaundice as well as in animals whose bile ducts have been ligated. Although there is some evidence indicating that bile acids can directly depress cardiac function at very high concentrations (IO-3M) it is not obvious whether bile acids have an inotropic effect on the heart at pathophysiological concentrations. In order to establish whether bile acids have an inotropic effect at these concentrations, we studied the effects of primary, conjugated and secondary bile acids (10-9-lO- M) on the contractile force (isometric twitch) and the electrophysiological properties (transmembrane action potential) of isolated rat ventri'cular muscle. Irrespective of type, all the bile acids caused a concentration dependent negative inotropic effect. For example, sodium taurocholate (NTC), IO-6M, reduced active tension, maximum rate of tension activation (+dT/dt) and maximum rate of tension relaxation (-dr/dr) by 22, 20 and 22% (p <0.05) respectively. These effects were associated with a concentration dependent shortening of the duration of the transmembrane action potential. NTC (IO-6M) reduced action potential duration at 30% and 50% repolarization by 30% and 38% (p <0.005) respectively, while other action potential characteristics were unaffected. In conclusion, bile acids in concentrations found in the plasma of cholestatic patients can directly affect cardiac contraction by inducing a negative inotropic effect mediated by a shortening of action potential duration. This effect may be a component of the physiological basis for the increased postoperatively susceptibility to shock of patients with obstructive jaundice.
PERISINUSOIDAL CELLS IN ALCOHOLIC PATIENTS WITH SUB-NORMAL LIVER HISTOLOGY. 32
P. Bioulac-Sage, F. Sztark, P. LatrT* J. Dubroca, A. Qulnton, C. Balabaud. Lab. Int. Cal. Universit~ de Bordeaux II et Service des maladies de l'appareil digestif, j~Spital St Andre, Bordeaux, France.
Perisinusoidal cells (PSC) store lipids (vit A) and are probably involved in fibrogenesis. In alcoholic patients (A) with perivenular and perisinusoidal fibrosis, PSC loose their lipids and acquire some of the characteristics of fibro-myofibroblasts (transitional cells). The aim of this study was to assess whether chronic alcohol consumption could induce PSC changes before the occurrence of fibrosis in some patients. In 8 A with or without steatosis but no fibrosis, part of the biopsy was fixed for routine histology and part was perfusion-fixed with glutaraldehyde. The following characteristics were measured : a) hepatic vein thickness (vein diameter
C PSC ( t o t a l ) V = 10-+2 I~ 3.6+-0.3 v
V = % of hepatic parenchyma X 10-3. v
A PSC (+) V = 9+-3 I= 2.8+-0.6 v
A PSC ( t o t a l ) V = 11+-3 I= 3.6+-0.7 v
I= PSC/fleld of O.02mm2.
V and I did not differ significantly in the 2 groups of patients although some k showed an v • increase in their I lipid ratio (I+/I total) : normal = 0.7+0.06. By EM, PSC(+) and (-) did not differ in A and C in particular PSC(-) were not transitional cells. In conclusion : i) in assessing lipids in PSC, it is important to consider the PSC index lipid ratio. 2) Alcohol does not seem to induce major PSO changes before it induces fibrosis.
$194
EFFECTS OF BILE ACIDS ON THE CARDIAC
Ofer Binah*, Arieh Bomzon** and Ori S. Better*** Rappaport Family Institute for Research in the Medical Sciences and Departments of Physiology and Biophysics* and Pharmacology**, Department of Nephrology, Rambam Medical Center*** and Faculty of Medicine, Technion, Haifa, Israel.
Depression of cardiovascular function occurs in patients with obstructive jaundice as well as in animals whose bile ducts have been ligated. Although there is some evidence indicating that bile acids can directly depress cardiac function at very high concentrations (IO-3M) it is not obvious whether bile acids have an inotropic effect on the heart at pathophysiological concentrations. In order to establish whether bile acids have an inotropic effect at these concentrations, we studied the effects of primary, conjugated and secondary bile acids (10-9-lO- M) on the contractile force (isometric twitch) and the electrophysiological properties (transmembrane action potential) of isolated rat ventri'cular muscle. Irrespective of type, all the bile acids caused a concentration dependent negative inotropic effect. For example, sodium taurocholate (NTC), IO-6M, reduced active tension, maximum rate of tension activation (+dT/dt) and maximum rate of tension relaxation (-dr/dr) by 22, 20 and 22% (p <0.05) respectively. These effects were associated with a concentration dependent shortening of the duration of the transmembrane action potential. NTC (IO-6M) reduced action potential duration at 30% and 50% repolarization by 30% and 38% (p <0.005) respectively, while other action potential characteristics were unaffected. In conclusion, bile acids in concentrations found in the plasma of cholestatic patients can directly affect cardiac contraction by inducing a negative inotropic effect mediated by a shortening of action potential duration. This effect may be a component of the physiological basis for the increased postoperatively susceptibility to shock of patients with obstructive jaundice.
PERISINUSOIDAL CELLS IN ALCOHOLIC PATIENTS WITH SUB-NORMAL LIVER HISTOLOGY. 32
P. Bioulac-Sage, F. Sztark, P. LatrT* J. Dubroca, A. Qulnton, C. Balabaud. Lab. Int. Cal. Universit~ de Bordeaux II et Service des maladies de l'appareil digestif, j~Spital St Andre, Bordeaux, France.
Perisinusoidal cells (PSC) store lipids (vit A) and are probably involved in fibrogenesis. In alcoholic patients (A) with perivenular and perisinusoidal fibrosis, PSC loose their lipids and acquire some of the characteristics of fibro-myofibroblasts (transitional cells). The aim of this study was to assess whether chronic alcohol consumption could induce PSC changes before the occurrence of fibrosis in some patients. In 8 A with or without steatosis but no fibrosis, part of the biopsy was fixed for routine histology and part was perfusion-fixed with glutaraldehyde. The following characteristics were measured : a) hepatic vein thickness (vein diameter
C PSC ( t o t a l ) V = 10-+2 I~ 3.6+-0.3 v
V = % of hepatic parenchyma X 10-3. v
A PSC (+) V = 9+-3 I= 2.8+-0.6 v
A PSC ( t o t a l ) V = 11+-3 I= 3.6+-0.7 v
I= PSC/fleld of O.02mm2.
V and I did not differ significantly in the 2 groups of patients although some k showed an v • increase in their I lipid ratio (I+/I total) : normal = 0.7+0.06. By EM, PSC(+) and (-) did not differ in A and C in particular PSC(-) were not transitional cells. In conclusion : i) in assessing lipids in PSC, it is important to consider the PSC index lipid ratio. 2) Alcohol does not seem to induce major PSO changes before it induces fibrosis.
$194