Effects of pentobarbital sodium anesthesia on splanchnic hemodynamics of normal and portal-hypertensive rats

Lee, S. S.; Girod, Catherine; Valla, Dominique; Geoffroy, Patrick; Lebrec, Didier

doi:10.1152/ajpgi.1985.249.4.g528

Cited by 39 publications

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“…Conversely, octreotide may induce a vasoconstriction if the drug is given in portal hypertensive rats with a baseline vasodilation. 13 Another peptide, atrial natriuretic peptide, has been shown to elicit either vasodilation or vasoconstriction, depending on the level of the pre-existing vascular tone. 15 In conclusion, octreotide decreased splanchnic and systemic vasoconstriction in portal hypertensive rats pre-treated with terlipressin.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac output and regional blood¯ows were measured by the radioactive microsphere method and the reference sample method as previously described. 12,13 For the ®rst set of haemodynamic measurements a precounted aliquot of » 60 000 16 1 lm diameter, 141 Ce-labelled, microspheres (speci®c activity of 10 lCi/g; New England Nuclear, Boston, MA, USA), suspended in Ficoll 70 (10% Pharmacia; Fine Chemicals AB, Uppsala, Sweden) and Tween-80 (0.01%) and ultrasonically agitated, was injected into the ventricular catheter and¯ushed with 1 mL of isotonic saline for 45 s. During the microsphere injection, a reference blood sample was drawn from the catheter in the femoral artery into a motor-driven syringe at 0.8 mL/ min for 1 min For the second set of haemodynamic measurements 113 Sn-labelled microspheres were injected using the same technique. The animal was then killed with an overdose of pentobarbital sodium.…”

Section: Haemodynamic Measurementsmentioning

confidence: 99%

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Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats

Moreau

Cailmail

Valla

et al. 1997

Aliment Pharmacol Ther

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INTRODUCTIONTerlipressin or somatostatin given alone are used as ®rst-line treatments of variceal haemorrhage. 1±9 These two substances act on the splanchnic circulation through different mechanisms. Terlipressin elicits a direct splanchnic vasoconstriction, 10 while somatostatin increases splanchnic vascular resistance by suppressing endogenous vasodilator peptides. 11 Therefore, a combination of terlipressin and octreotide may have more marked splanchnic haemodynamic effects than either substance alone. On the other hand, as both terlipressin 10 and somatostatin 12 decrease cardiac index, a combination of these drugs may result in a dangerous decrease in this value. Thus, more information is necessary on the haemodynamic effects of the combination of terlipressin and somatostatin. The aim SUMMARY Background: An enhancement of the haemodynamic effects of terlipressin by octreotide (and vice versa) may be useful in the treatment of portal hypertension. The aim of this study was to investigate the short-term effects of terlipressin, octreotide or a combination of these substances on splanchnic and systemic haemodynamics in rats with portal vein stenosis. Methods: Eight rats received an intravenous (i.v.) infusion of isotonic saline (10 lL/min for 15 min). Eight rats received terlipressin ®rst (0.05 mg/kg) and then an i.v. infusion of octreotide (8 lg.h/kg for 15 min) 15 min later. Eight other rats ®rst received an i.v. infusion of octreotide and then terlipressin 15 min later. Splanchnic and systemic haemodynamics (radioactive microsphere method) were measured after saline, after terlipressin or octreotide alone, and after the combined treatments. Results: Terlipressin and octreotide alone signi®cantly decreased portal pressure, portal tributary blood¯ow

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Section: Discussionmentioning

confidence: 99%

Section: Haemodynamic Measurementsmentioning

confidence: 99%

Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats

Moreau

Cailmail

Valla

et al. 1997

Aliment Pharmacol Ther

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“…For this, haemodynamic values were measured prior to and 20min after the intracerebroventricular administration (Wright et al, 1986) Haemodynamic studies were performed in conscious unrestrained rats. Cardiac index and regional blood flows were measured by the radioactive microsphere method and the reference sample method as previously described (Lee et al, 1985). For the first set of haemodynamic measurements, a precounted aliquot of approximately 60,000, 16+ 1 I m diameter, "'Ce-labelled microspheres (sp.…”

Section: Protocolsmentioning

confidence: 99%

Effects of glibenclamide on systemic and splanchnic haemodynamics in conscious rats

Moreau

Komeichi

Kirstetter

et al. 1994

British J Pharmacology

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1 The effects of the sulphonylurea, glibenclamide (20 mg kg ', i.v.), at a dose that blocks vascular potassium channels, on systemic and splanchnic haemodynamics (radioactive microspheres) were studied in conscious rats. 2 Glibenclamide significantly decreased cardiac index and hepatic artery blood flow while it significantly increased vascular resistance in systemic, portal and hepatic arterial territories. 3 In rats with suppressed cardiovascular reflexes, glibenclamide induced vasoconstriction in systemic, portal and hepatic arterial territories. 4 Intracerebroventricular administration of glibenclamide did not alter systemic or regional vascular tone.5 Glibenclamide blunted the vasodilator effect of the potassium channel opener, diazoxide but not that of the L-type calcium channel blocker, nicardipine. 6 Another sulphonylurea, glipizide (20 mg kg-', i.v.), induced significant systemic and splanchnic vasoconstriction. 7 Thus, the glibenclamide-induced blockade of vascular potassium channels caused a vasoconstriction in the systemic and splanchnic vascular beds. In these territories, therefore, the opening of glibenclamide-sensitive potassium channels might be responsible for a basal vasodilator tone.

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“…The second group contained 16 rats with portal hypertension induced by the partial ligation of the portal vein, as previously described. 18 The hemodynamic study was performed 2 weeks later, when portal hypertension had fully developed. The third group contained 16 rats with secondary biliary cirrhosis caused by bile duct ligation.…”

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Beneficial hemodynamic effects of bosentan, a mixed ETA and ETB receptor antagonist, in portal hypertensive rats

et al. 1998

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In patients with cirrhosis, the plasma level of endothelin, a potent vasoconstrictor peptide, is elevated, and endothelin plays a role in increased intrahepatic vascular resistance. Thus, the aim of this study was to evaluate the hemodynamic effects of bosentan, a mixed ET A and ET B endothelin receptor antagonist in three models of portal hypertension. In all groups of rats, endothelin (2 g/kg intravenously) administration significantly increased intrahepatic vascular resistance. In rats with secondary biliary cirrhosis, bosentan (30 mg/kg) significantly reduced portal pressure from 14.6 ؎ 1.2 to 12.1 ؎ 0.6 mm Hg, while portal blood flow and cardiac output increased by 45% and 57%, respectively. Thus, hepatocollateral vascular resistance decreased significantly from 177 ؎ 19 to 101 ؎ 9 dyn · s · cm ؊5 ؋ 10 ؊3 . Similar results were observed in rats with CCl 4 -induced cirrhosis. In isolated perfused cirrhotic rat livers, bosentan (1 to 100 mol/L) had no significant effect on hepatic vascular resistance. In portal vein-stenosed rats, bosentan administration significantly decreased portal pressure from 13.1 ؎ 0.6 to 11.4 ؎ 0.5 mm Hg by reducing portosystemic vascular resistance, because bosentan had no effect on vascular resistance of normal rat liver. In conclusion, bosentan administration decreased portal pressure in vivo by reducing hepatocollateral vascular resistance in rats with cirrhosis. Thus, mixed endothelin receptor antagonists might be a new approach in the pharmacological treatment of portal hypertension. (HEPATOLOGY 1998;28:655-659.)Numerous studies have found that plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) are increased in patients with cirrhosis and are related to the severity of the liver disease. 1-8 Despite this, these patients have low arterial pressure and systemic vascular resistance. This discrepant finding may be caused, at least in part, by a vascular hyporesponsiveness to endothelins that has been identified in cirrhotic rats. 9,10 Moreover, it has been shown that endothelins induce sinusoidal vasoconstriction through both ET A and ET B receptors and increase intrahepatic vascular resistance in the normal and perfused cirrhotic liver. [11][12][13][14][15] These results suggest that endothelins play a role in the mechanism of intrahepatic portal hypertension. Thus, administration of the mixed ET A and ET B receptor antagonist, 16,17 bosentan, may decrease intrahepatic vascular resistance and decrease portal hypertension. The aim of this study was to evaluate the acute hemodynamic effect of both bosentan and endothelin in two animal models of cirrhosis and in one model with extrahepatic portal hypertension. MATERIALS AND METHODSAnimals. Sixty-four male Sprague-Dawley rats (Charles River Laboratories, Saint-Aubin-lès-Elbeuf, France) were divided into four groups. The first group contained 16 normal rats. The second group contained 16 rats with portal hypertension induced by the partial ligation of the portal vein, as previously described. 18 The hemodynamic study w...

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Effects of pentobarbital sodium anesthesia on splanchnic hemodynamics of normal and portal-hypertensive rats

Cited by 39 publications

References 0 publications

Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats

Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats

Effects of glibenclamide on systemic and splanchnic haemodynamics in conscious rats

Beneficial hemodynamic effects of bosentan, a mixed ETA and ETB receptor antagonist, in portal hypertensive rats

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