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39 STUDY ON THE INTRADIEM ACTIVITY OF THE ADRENERGIC SYSTEM IN CIRRHOSIS. RELATIONSHIP WITH RENIN ACTIVITY AND SYSTEMIC HAEMODYNAMICS. M. Bernardi, F. Trevisani t C. Santini 7 R. DePalma t A. Ligabue~ M. Ba- raldini~ G. Gasbarrini. Patologia Medica III, Univ. of Bologna;*Lab. Analisi, Osp. M. Malpighi Intradiem activity of the adrenergic system was investigated in 7 controls and cirrhotics without (7) and with (9) ascites by determining urinary norepine- phrine (UNEV) and vanylmandelic acid (UVMAY) excretions 6 hourly, while supine Plasma renin activity (PRA), mean arterial pressure (AP), heart rate (HR) were also evaluated 4 hourly. UNE V and UVMA V decreased at night in controls, as ex- pected, but increased significanlty in compensated patients. Cirrhotics with ascites had higher levels than controls through the whole day. Compensated pa- tients had normal AP, slighty increased HR (ns) and reduced PRA (p40.05). In cirrhotics with ascites AP was decreased and HR and PRA increased (p~O.05). AP was never related to U V, but was inversely correlated with PRA (p<O.05) in ascitic patients. On the contrary HR was direct function of U V both in com- pensated and decompensated cirrhotics (p<O.05). Both catecholamine synthesis (UvMAV) and release (UNE V) are increased in cirrhosis with ascites, but deran- gements in the renal excretion pattern of NE and VMA are already present in compensated patients. In spite of the increased adrenergic activity AP is de- creased in ascitic patients and thus a possible main cause of renin release. These data suggest a reduced vascular response to sympathetic stimulation,wh~ reas #-receptor mediated response still is preserved under steady state. 40 LIVER PERISINUSOIDAL FIBROSIS IN THE SPONTANEOUSLY DIABETIC "BB" WISTAR RAT D. Bernuau ~ R. Guillot ° , A.M. Durand-Schneider , P. Poussier °° , A. Moreau, G. Feldmann INSERM U 24, HSpital Beaujon, Clichy, "Laboratoire d'Embryologie, UER Biom~dicale des Saints-P~res, Paris, France and °"Nutrition & Food Sciences Center, Royal Victoria Hospital, Montreal, Quebec, Canada. Perisinusoidal fibrosis has been described in the liver of patients with insulin-dependent diabetes. To investigate further the relationship between this lesion and type I diabetes, we studied the structure of liver sinusoids in a genetically susceptible strain of rats, the "BB" Wistar rats, which develop a spontaneous diabetes strikingly similar to human type I diabetes. Fourteen "BB" Wistar rats, 7 with insulin-treated diabetes (group I) and 7 without diabetes (group II), and 7 control "non BB" Wistar rats, were studied. Light and electron microscopic examination of liver samples was performed. Sami-quantitation of abnormalities of the sinusoi- dal collagen framework was made on trichrome-stained sections. The point-counting method was used to quantify perisinusoidal fibrosis at the ultrastructural level. All control "non BB" Wistar rats had a normal liver at the optical and ultrastructural levels ; collagen fibers occupied 1.75 ± 0.24 % of the sinusoidal volume. Eleven (78 %) "BB" Wistar rats (6 rats of group I and '5 rats of group II) displayed localized thickenings of the sinusoids, with ultras- tructurally abundant perisinusoidal deposits of collagen fibers, and elevated percentages of collagen fibers per sinusoid unit (3.16 to 12.32 %) compared to controls. Fibrous septae (2 rats in group I and 5 rats in group IX) and cirrhosis (2 rats in group I) were also visible. Three "BB" rats were normal. In summary, liver perisinusoidal fibrosis is a frequent lesion in "BB" Wistar rats. Septum formation and cirrhosis may also be found. These lesions are strain-related, and clearly inde- pendent of the presence of diabetes. Liver perisinusoidal fibrosis in patients with type I diabetes might likewise represent a distinct, genetically-dependent collagen abnormality. $20

Liver perisinusoidal fibrosis in the spontaneously diabetic “BB” wistar rat

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Page 1: Liver perisinusoidal fibrosis in the spontaneously diabetic “BB” wistar rat

39 STUDY ON THE INTRADIEM ACTIVITY OF THE ADRENERGIC SYSTEM IN CIRRHOSIS.

RELATIONSHIP WITH RENIN ACTIVITY AND SYSTEMIC HAEMODYNAMICS.

M. Bernardi, F. Trevisani t C. Santini 7 R. DePalma t A. Ligabue~ M. Ba-

raldini~ G. Gasbarrini.

Patologia Medica III, Univ. of Bologna;*Lab. Analisi, Osp. M. Malpighi

Intradiem activity of the adrenergic system was investigated in 7 controls and

cirrhotics without (7) and with (9) ascites by determining urinary norepine-

phrine (UNEV) and vanylmandelic acid (UVMAY) excretions 6 hourly, while supine

Plasma renin activity (PRA), mean arterial pressure (AP), heart rate (HR) were

also evaluated 4 hourly. UNE V and UVMA V decreased at night in controls, as ex-

pected, but increased significanlty in compensated patients. Cirrhotics with

ascites had higher levels than controls through the whole day. Compensated pa-

tients had normal AP, slighty increased HR (ns) and reduced PRA (p40.05). In

cirrhotics with ascites AP was decreased and HR and PRA increased (p~O.05). AP

was never related to U V, but was inversely correlated with PRA (p<O.05) in

ascitic patients. On the contrary HR was direct function of U V both in com-

pensated and decompensated cirrhotics (p<O.05). Both catecholamine synthesis

(UvMAV) and release (UNE V) are increased in cirrhosis with ascites, but deran-

gements in the renal excretion pattern of NE and VMA are already present in

compensated patients. In spite of the increased adrenergic activity AP is de-

creased in ascitic patients and thus a possible main cause of renin release.

These data suggest a reduced vascular response to sympathetic stimulation,wh~

reas #-receptor mediated response still is preserved under steady state.

40 LIVER PERISINUSOIDAL FIBROSIS IN THE SPONTANEOUSLY DIABETIC "BB" WISTAR RAT

D. Bernuau ~ R. Guillot ° , A.M. Durand-Schneider , P. Poussier °° , A. Moreau, G. Feldmann INSERM U 24, HSpital Beaujon, Clichy, "Laboratoire d'Embryologie, UER Biom~dicale des

Saints-P~res, Paris, France and °"Nutrition & Food Sciences Center, Royal Victoria Hospital, Montreal, Quebec, Canada.

Perisinusoidal fibrosis has been described in the liver of patients with insulin-dependent diabetes. To investigate further the relationship between this lesion and type I diabetes, we studied the structure of liver sinusoids in a genetically susceptible strain of rats, the "BB" Wistar rats, which develop a spontaneous diabetes strikingly similar to human type I diabetes. Fourteen "BB" Wistar rats, 7 with insulin-treated diabetes (group I) and 7 without diabetes (group II), and 7 control "non BB" Wistar rats, were studied. Light and electron microscopic examination of liver samples was performed. Sami-quantitation of abnormalities of the sinusoi- dal collagen framework was made on trichrome-stained sections. The point-counting method was used to quantify perisinusoidal fibrosis at the ultrastructural level. All control "non BB" Wistar rats had a normal liver at the optical and ultrastructural levels ; collagen fibers occupied 1.75 ± 0.24 % of the sinusoidal volume. Eleven (78 %) "BB" Wistar rats (6 rats of group I and '5 rats of group II) displayed localized thickenings of the sinusoids, with ultras- tructurally abundant perisinusoidal deposits of collagen fibers, and elevated percentages of collagen fibers per sinusoid unit (3.16 to 12.32 %) compared to controls. Fibrous septae (2 rats in group I and 5 rats in group IX) and cirrhosis (2 rats in group I) were also visible. Three "BB" rats were normal.

In summary, liver perisinusoidal fibrosis is a frequent lesion in "BB" Wistar rats. Septum formation and cirrhosis may also be found. These lesions are strain-related, and clearly inde- pendent of the presence of diabetes. Liver perisinusoidal fibrosis in patients with type I diabetes might likewise represent a distinct, genetically-dependent collagen abnormality.

$20