Effects of propranolol on venous compliance in conscious rats with pre-hepatic portal hypertension

García‐Pagán, Juan Carlos; Lionetti, Raffaela; Piera, Carlos; Abraldes, Juan G.; Bosch, Jaume

doi:10.1016/j.jhep.2005.10.024

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…Besides these human studies, two rat studies have also examined the total vascular capacitance in a similar manner, with rapid volume infusions in the CCl 4 -cirrhotic rat (7) or infusions and withdrawal in the prehepatic portal-hypertensive rat (1). The Ingles et al study (7) found increased capacitance but no change in compliance in the cirrhotic rat, whereas the Andreu et al study (1) reported increased compliance. Thus all four previous studies are consistent in showing an enhanced capacitance or compliance of the overall systemic veins in cirrhosis and portal hypertension.…”

Section: Discussionmentioning

confidence: 94%

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Yang

Liu²,

Gaskari³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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In cirrhosis, despite augmented blood volume, effective circulating volume is decreased. This implies abnormal regulation of blood volume, i.e., venous pooling. Because gut veins are the main blood reservoir, we studied mesenteric venous capacitance and compliance in a rat model of cirrhosis. Cirrhosis was induced by bile duct ligation (4 wk). Controls were sham operated. Changes in first-order mesenteric vein diameters induced by drugs, hemorrhage, and stepwise increases in portal pressure (inflatable cuff) were directly observed by intravital microscopy. Effects of nitric oxide on responses to acute graded hemorrhage were studied by use of selective NO synthase (NOS) isoform inhibitors. Pressures were related to diameters to assess capacitance and compliance. Compared with controls, cirrhotic rats demonstrated increased mesenteric venous capacitance and decreased compliance. Norepinephrine induced venoconstriction but did not affect compliance. Prazosin markedly diminished compliance in controls but not cirrhotics. Conversely, the nonspecific NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) decreased compliance in cirrhotics, but not controls. Tetrodotoxin venodilated controls, venoconstricted cirrhotics, and markedly decreased compliance in both groups. When hemorrhaged, controls rapidly venoconstricted to compensate for initial hypotension, whereas cirrhotic rats remained hypotensive because venoconstriction was severely blunted. Pretreatment with l-NAME or the selective neuronal NOS inhibitors S-methyl-l-thiocitrulline and 7-nitroindazole normalized the homeostatic responses of cirrhotic rats, whereas the selective endothelial-constitutive NOS inhibitor N-iminoethyl-l-ornithine did not affect the response. In conclusion, mesenteric veins of cirrhotic rats showed enhanced capacitance, attenuated compensatory constrictive response to hemorrhage, and decreased compliance. The first two abnormalities were caused by neuronal NOS-derived nitric oxide.

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Section: Discussionmentioning

confidence: 94%

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Yang

Liu²,

Gaskari³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This is also what occurred in previous studies assessing the acute effect of bblockers in patients with and in those without varices. 18,26 It has been shown that such a marked effect on free hepatic venous pressure is, at least in part, related to a significant decrease of total venous compliance, 28,29 which is markedly increased in cirrhosis. 30 The present study suggests that such an increase in venous compliance occurs early in the course of compensated cirrhosis, even before reaching the level of CSPH.…”

Section: Discussionmentioning

confidence: 99%

Development of hyperdynamic circulation and response to β‐blockers in compensated cirrhosis with portal hypertension

et al. 2015

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Nonselective b-blockers are useful to prevent bleeding in patients with cirrhosis and large varices but not to prevent the development of varices in those with compensated cirrhosis and portal hypertension (PHT). This suggests that the evolutionary stage of PHT may influence the response to b-blockers. To characterize the hemodynamic profile of each stage of PHT in compensated cirrhosis and the response to b-blockers according to stage, we performed a prospective, multicenter (tertiary care setting), cross-sectional study. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273 patients with compensated cirrhosis before and after intravenous propranolol (0.15 mg/kg): 194 patients had an HVPG !10 mm Hg (clinically significant PHT [CSPH]), with either no varices (n 5 80) or small varices (n 5 114), and 79 had an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver stiffness (P < 0.001), worse Model for End-Stage Liver Disease score (P < 0.001), more portosystemic collaterals (P 5 0.01) and splenomegaly (P 5 0.01) on ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT. Patients with CSPH had lower systemic vascular resistance (1336 6 423 versus 1469 6 335 dyne Á s Á cm -5 , P < 0.05) and higher cardiac index (3.3 6 0.9 versus 2.8 6 0.4 L/min/m 2 , P < 0.01). After propranolol, the HVPG decreased significantly in both groups, although the reduction was greater in those with CSPH (-16 6 12% versus -8 6 9%, P < 0.01). The HVPG decreased !10% from baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001) and decreased !20% in 40% versus 13%, respectively (P 5 0.001). Conclusion: Patients with subclinical PHT have less hyperdynamic circulation and significantly lower portal pressure reduction after acute b-blockade than those with CSPH, suggesting that b-blockers are more suitable to prevent decompensation of cirrhosis in patients with CSPH than in earlier stages. (HEPATOLOGY 2016;63:197-206) P ortal hypertension (PHT) is the most common complication of cirrhosis and the main determinant for developing varices or clinical decompensation (appearance of ascites, variceal bleeding, or hepatic encephalopathy). Decompensation, in turn, is the leading cause of mortality in cirrhosis. 1,2 The primary factor in the development of PHT in cirrhosis is an increased vascular resistance to portal flow through Abbreviations: CI, confidence interval; CO, cardiac output; CSPH, clinically significant portal hypertension; HR, heart rate; HVPG, hepatic venous pressure gradient; MELD, Model for End-Stage Liver Disease; PHT, portal hypertension; RCT, randomized controlled trial; SVR, systemic vascular resistance.From the

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Combined use of propranolol and nifedipine offers better effects on portal vein nonuniform remodeling in carbon tetrachloride (CCl4)-induced portal hypertensive rats

Zhang

Shi

et al. 2009

European Journal of Pharmacology

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Effects of propranolol on venous compliance in conscious rats with pre-hepatic portal hypertension

Cited by 5 publications

References 28 publications

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

Development of hyperdynamic circulation and response to β‐blockers in compensated cirrhosis with portal hypertension

Combined use of propranolol and nifedipine offers better effects on portal vein nonuniform remodeling in carbon tetrachloride (CCl4)-induced portal hypertensive rats

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