Vascular NE responsiveness in portal hypertension: role of portal pressure and portosystemic shunting

1994 ◽  
Vol 266 (3) ◽  
pp. H1162-H1168 ◽  
Author(s):  
Z. Y. Wu ◽  
J. N. Benoit
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Pressure ◽  
Portacaval Shunt ◽  
Effective Dosage ◽  
Sprague Dawley ◽  
Blood Flow Reduction ◽  
Portosystemic Shunting ◽  
Venous Collaterals ◽  
On Line

Previous studies have suggested that the development of portal venous collaterals and subsequent portosystemic shunting is the key event responsible for the reduced vasoconstrictor effectiveness in chronic portal hypertension. The purpose of the present study was to test this hypothesis. Thirty-nine male Sprague-Dawley rats were divided into four groups: end-to-side portacaval shunt (PCS, n = 11), chronic prehepatic portal hypertension (CPH, n = 10), acute prehepatic portal hypertension (APH, n = 8), and sham-operated controls (Sham, n = 10). The small intestine was prepared for microcirculatory studies. First-order arteriolar diameter and erythrocyte velocity were measured on-line, and blood flow was subsequently calculated. Once steady-state values were obtained the preparation was topically exposed to incremental doses of norepinephrine. The half-maximal effective dosage (ED50) for maximal vasoconstriction (diameter response) was significantly increased in PCS (4.5 microM) and CPH (1.5 microM) compared with Sham (0.8 microM). However, the ED50 was significantly lower in APH (0.17 microM) than in Sham. Similarly the ED50 for maximal blood flow reduction was higher in PCS (2.4 microM) and CPH (1.2 microM) compared with Sham (0.2 microM). The results demonstrate that vascular norepinephrine responsiveness is reduced in both portacaval shunted and chronic portal hypertensive rats, but not in acute portal hypertension. These data indicate that portosystemic shunting, not portal pressure elevation, is the key event leading to the reduced vascular norepinephrine responsiveness observed in CPH conditions.

Bile acids do not mediate the hyperdynamic circulation in portal hypertensive rats

1990 ◽  
Vol 259 (1) ◽  
pp. G21-G25 ◽  
Author(s):  
P. Genecin ◽  
J. Polio ◽  
L. A. Colombato ◽  
G. Ferraioli ◽  
A. Reuben ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Mean Arterial Pressure ◽  
Bile Acids ◽  
Portal Pressure ◽  
Control Group ◽  
Portal Vein Ligation ◽  
Hypertensive Rats ◽  
Hyperdynamic Circulation ◽  
Portosystemic Shunting

Portal hypertension is accompanied by hyperdynamic systemic and splanchnic circulation. Serum bile acids (BAs), which are elevated in portal hypertension and have vasodilatory properties, have been proposed as mediators of this hyperdynamic circulation. In this study, portal hypertensive rats [accomplished by partial portal vein ligation (PVL)] were gavaged with cholestyramine (PVL-CH) to decrease circulating BA levels. A control group of rats was gavaged with an inert suspension of Metamucil (PVL-ME). The following hyperdynamic parameters were found to be similar in PVL-CH and PVL-ME: mean arterial pressure (119 +/- 6 vs. 124 +/- 5 mmHg), portal pressure (13.2 +/- 0.6 vs. 14.5 +/- 0.5 mmHg), cardiac index (0.33 +/- 0.04 vs. 0.34 +/- 0.03 ml.min-1.g body wt-1), splanchnic blood flow (1.4 +/- 0.13 vs. 1.6 +/- 0.1 ml.min-1.g body wt-1), portosystemic shunting (82 +/- 8 vs. 92 +/- 3%), peripheral arteriolar resistances (344 +/- 74 vs. 387 +/- 29 mmHg.min.ml-1.g body wt), and splanchnic arteriolar resistances (75 +/- 14 vs. 72 +/- 6 mmHg.min.ml-1.g splanchnic wt; 1,471 +/- 150 vs. 1,325 +/- 120 mmHg.min.ml-1.g body wt). BA in PVL-ME (84 +/- 9 microM/l) were similar to those previously observed in untreated PVL and significantly greater than those measured in PVL-CH (25 +/- 4 microM/l; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

On-Line Monitoring of Sequential Blood Flow Reduction during Splenic Embolization

1989 ◽  
Vol 30 (1) ◽  
pp. 101-103 ◽  
Author(s):  
D. P. Link ◽  
J. A. Seibert ◽  
J. Gould ◽  
B. M. T. Lantz
Keyword(s):  
Blood Flow ◽  
Clinical Results ◽  
Dilution Technique ◽  
Embolic Material ◽  
Flow Reduction ◽  
Blood Flow Reduction ◽  
Splenic Embolization ◽  
Predetermined Level ◽  
On Line ◽  
Different Levels

Partial embolization of the spleen has been well established for the treatment of hypersplenism. A weakness of the technique is the lack of an objective method to quantitate the flow reduction during the procedure. The video dilution technique (VDT) has earlier been used to measure blood flow in regional arteries using video cassette replay. By adapting the VDT concept of relative flow to digital subtraction angiography, it is possible to calculate the flow reduction instantly following each injection of embolic material. We present a case of partial splenic embolization where the flow in the splenic artery was reduced to a predetermined level of 50 per cent of baseline flow. The clinical results were excellent. By observing the clinical results of partial embolization, terminated at different levels of flow reduction, it will be possible to optimize the results and prevent overembolization.

Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model

1985 ◽  
Vol 248 (6) ◽  
pp. G618-G625 ◽  
Author(s):  
E. Sikuler ◽  
D. Kravetz ◽  
R. J. Groszmann
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Rat Model ◽  
Portal Pressure ◽  
Portal System ◽  
Hypertensive Rats ◽  
Hemodynamic Changes ◽  
Sequence Of Events ◽  
Radioactive Microsphere

In rats with portal hypertension induced by partial ligation of the portal vein, we have recently demonstrated an increased portal venous inflow that becomes an important factor in the maintenance of portal hypertension. The sequence of events that leads into this circulatory disarray is unknown. We evaluated chronologically the chain of hemodynamic changes that occurred after portal hypertension was induced by partial ligation of the portal vein. In this model it is possible to follow, from the initiation of the portal-hypertensive state, the interaction between blood flow and resistance in the portal system as well as the relation between the development of portal-systemic shunting and the elevated portal venous inflow. The study was performed in 45 portal-hypertensive rats and in 29 sham-operated rats. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. The constriction of the portal vein was immediately followed by a resistance-induced portal hypertension characterized by increased portal resistance (9.78 +/- 0.89 vs. 4.18 +/- 0.71 dyn X s X cm-5 X 10(4), mean +/- SE, P less than 0.01), increased portal pressure (17.7 +/- 0.9 vs. 9.5 +/- 0.6 mmHg, P less than 0.001), and decreased portal venous inflow (3.93 +/- 0.26 vs. 6.82 +/- 0.49 ml X min-1 X 100 g body wt-1, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of thromboxane A2 in early BDL-induced portal hypertension

2003 ◽  
Vol 284 (3) ◽  
pp. G453-G460 ◽  
Author(s):  
Yukihiro Yokoyama ◽  
Hongzhi Xu ◽  
Nicole Kresge ◽  
Steve Keller ◽  
Amir H. Sarmadi ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Pressure ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Bicarbonate Buffer ◽  
Constant Flow Rate ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Cox 2

Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A2 (TXA2) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA2 in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate. After 30 min of nonrecirculating perfusion, the buffer was recirculated in a total volume of 100 ml. The perfusate was sampled for the enzyme immunoassay of thromboxane B2(TXB2), the stable metabolite of TXA2. Although recirculation of the buffer caused no significant change in sham-operated rats, it resulted in a marked increase in portal pressure in BDL rats. The increase in portal pressure was found concomitantly with a significant increase of TXB2 in the perfusate (sham vs. BDL after 30 min of recirculating perfusion: 1,420 ± 803 vs. 10,210 ± 2,950 pg/ml; P < 0.05). Perfusion with a buffer containing indomethacin or gadolinium chloride for inhibition of cyclooxygenase (COX) or Kupffer cells, respectively, substantially blocked the recirculation-induced increases in both portal pressure and TXB2 release in BDL group. Hepatic detection of COX gene expression by RT-PCR revealed that COX-2 but not COX-1 was upregulated following BDL, and this upregulation was confirmed at the protein level by Western blot analysis. In conclusion, these results clearly demonstrate that increased hepatic TXA2 release into the portal circulation contributes to the increased portal resistance in BDL-induced liver injury, suggesting a role of TXA2 in liver fibrosis-induced portal hypertension. Furthermore, the Kupffer cell is likely the source of increased TXA2, which is associated with upregulation of the COX-2 enzyme.

scholarly journals Restoration of liver sinusoidal cell phenotypes by statins improves portal hypertension and histology in rats with NASH

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Miren Bravo ◽  
Imma Raurell ◽  
Diana Hide ◽  
Anabel Fernández-Iglesias ◽  
Mar Gil ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Endothelial Dysfunction ◽  
Control Diet ◽  
Portal Pressure ◽  
Developed Countries ◽  
Liver Disorder ◽  
Statin Treatment ◽  
Liver Sinusoidal Endothelial Cell ◽  
Sprague Dawley ◽  
Sinusoidal Cell

AbstractNon-alcoholic steatohepatitis (NASH) is a common chronic liver disorder in developed countries, with the associated clinical complications driven by portal hypertension (PH). PH may precede fibrosis development, probably due to endothelial dysfunction at early stages of the disease. Our aim was to characterize liver sinusoidal endothelial cell (LSEC) dedifferentiation/capillarization and its contribution to PH in NASH, together with assessing statins capability to revert endothelial function improving early NASH stages. Sprague-Dawley rats were fed with high fat glucose-fructose diet (HFGFD), or control diet (CD) for 8 weeks and then treated with simvastatin (sim) (10 mg·kg−1·day−1), atorvastatin (ato) (10 mg·kg−1·day−1) or vehicle during 2 weeks. Biochemical, histological and hemodynamic determinations were carried out. Sinusoidal endothelial dysfunction was assessed in individualized sorted LSEC and hepatic stellate cells (HSC) from animal groups and in whole liver samples. HFGFD rats showed full NASH features without fibrosis but with significantly increased portal pressure compared with CD rats (10.47 ± 0.37 mmHg vs 8.30 ± 0.22 mmHg; p < 0.001). Moreover, HFGFD rats showed a higher percentage of capillarized (CD32b−/CD11b−) LSEC (8% vs 1%, p = 0.005) showing a contractile phenotype associated to HSC activation. Statin treatments caused a significant portal pressure reduction (sim: 9.29 ± 0.25 mmHg, p < 0.01; ato: 8.85 ± 0.30 mmHg, p < 0.001), NASH histology reversion, along with significant recovery of LSEC differentiation and a regression of HSC activation to a more quiescent phenotype. In an early NASH model without fibrosis with PH, LSEC transition to capillarization and HSC activation are reverted by statin treatment inducing portal pressure decrease and NASH features improvement.

Intestinal microvascular responsiveness to norepinephrine in chronic portal hypertension

1991 ◽  
Vol 260 (4) ◽  
pp. H1135-H1143 ◽  
Author(s):  
T. Joh ◽  
D. N. Granger ◽  
J. N. Benoit
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Dose Response ◽  
Vessel Diameter ◽  
Maximal Response ◽  
Hypertensive Rats ◽  
Response Curves ◽  
Cross Sectional ◽  
On Line

Effects of chronic prehepatic portal hypertension on intestinal microvascular sensitivity to norepinephrine (NE) were studied. Normal and portal hypertensive rats were anesthetized, and the intestine was prepared for in vivo microscopic observation. The preparation was transferred to a video microscope and a first-, second-, or third-order submucosal arteriole (i.e., 1A, 2A, or 3A, respectively) selected for study. Microvascular diameter and arteriolar erythrocyte velocity were measured on-line, and arteriolar blood flow was subsequently calculated as the product of velocity and vessel cross-sectional area. Once steady-state conditions were reached, the preparation was exposed to incremental doses of NE and microvessel responses were recorded. Cumulative log dose-response curves relating the change in arteriolar blood flow and vessel diameter to NE concentration were constructed for each group of arterioles and the ED50 for maximal response obtained from each dose-response relationship. NE ED50 for 1A blood flow was significantly higher in portal hypertensive rats (2.57 +/- 0.25 microM) compared with control rats (1.48 +/- 0.19 microM). Analysis of the diameter responses of 1A, 2A, and 3A indicated that the loss of vascular NE sensitivity in chronic portal hypertension was localized to the terminal submucosal arterioles (2A and 3A). No differences in the diameter response of 1A were observed between normal and portal hypertensive rats. Separate experiments were conducted to test if glucagon, a known mediator of the hyperdynamic intestinal circulation in portal hypertension, could acutely alter NE responsiveness in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Preeminence of Lesser Splanchnic Blood Flow in Selected Patients With Generalized Portal Hypertension

HPB Surgery ◽  
1990 ◽  
Vol 2 (4) ◽  
pp. 233-251
Author(s):  
Charles L. Witte ◽  
Marlys H. Witte ◽  
Gerald D. Pond
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Left Renal Vein ◽  
Signs And Symptoms ◽  
Operative Management ◽  
Gastric Varices ◽  
Coronary Vein ◽  
Clinical Complications ◽  
Arterial Inflow ◽  
Venous Collaterals

Although restricted transhepatic portal flow is necessary for development of generalized portal hypertension (GPH), increased splanchnic arterial inflow also contributes to GPH and its clinical sequelae. In this context, we describe 7 male and 6 female patients (mean age 48 years) in whom the lesser splanchnic (gastrosplenic) system played a key role in the signs and symptoms of GPH. These 13 patients (9 with hepatic cirrhosis, 3 with primary myeloproliferative disorder, and 1 with extrahepatic portal block) shared common features of massive splenomegaly, huge splenofundic gastric varices, often with a prominent natural shunt to the left renal vein. Total or near total splenectomy alone or combined where appropriate with coronary vein ligation was effective in controlling varix hemorrhage (10 patients), ascites (3), or complications of an enlarged spleen-anorexia and abdominal pain (3), hemolytic anemia (1) and profound thrombocytopenia with severe epistaxis (1). Intraoperative jejunal portal venography was crucial in operative management in order to establish definitively the presence or absence of coronary venous collaterals, and when present, to verify their operative ligation.These distinctive patients illustrate: 1) GPH is a heterogeneous syndrome of divergent splanchnic circulatory patterns, a feature which should be taken into account in selecting operative treatment; 2) one well-defined subgroup displays prominent hyperdynamic lesser splanchnic and specifically, splenic blood flow as a major contributor to clinical complications; and 3) within this subgroup, splenectomy combined with documented absence or surgical interruption of coronary venous collaterals as corroborated by intraoperative portography is effective alternative treatment.

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