The potential role of vascular alterations and subsequent impaired liver blood flow and hepatic hypoxia in the pathophysiology of non-alcoholic steatohepatitis

2019 ◽  
Vol 122 ◽  
pp. 188-197 ◽  
Author(s):  
D. van der Graaff ◽  
W.J. Kwanten ◽  
S.M. Francque
Keyword(s):  
Blood Flow ◽  
Potential Role ◽  
Liver Blood Flow ◽  
Alcoholic Steatohepatitis ◽  
Impaired Liver

scholarly journals Potential role of angiotensin II in noise-induced increases in inner ear blood flow

1985 ◽  
Vol 17 (1) ◽  
pp. 41-46 ◽  
Author(s):  
John W. Wright ◽  
Harold A. Dengerink ◽  
Josef M. Miller ◽  
Paul C. Goodwin
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Inner Ear ◽  
Potential Role ◽  
Inner Ear Blood Flow

scholarly journals Validation of Pharmacological Protocols for Targeted Inhibition of Canalicular MRP2 Activity in Hepatocytes Using [99mTc]mebrofenin Imaging in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 486
Author(s):  
Solène Marie ◽  
Irene Hernández-Lozano ◽  
Louise Breuil ◽  
Wadad Saba ◽  
Anthony Novell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Biliary Excretion ◽  
Low Dose ◽  
Organic Anion ◽  
Liver Blood Flow ◽  
High Dose ◽  
Liver Uptake ◽  
Targeted Inhibition ◽  
Substrate Inhibitor

The multidrug resistance-associated protein 2 (MRP2) mediates the biliary excretion of drugs and metabolites. [99mTc]mebrofenin may be employed as a probe for hepatic MRP2 activity because its biliary excretion is predominantly mediated by this transporter. As the liver uptake of [99mTc]mebrofenin depends on organic anion-transporting polypeptide (OATP) activity, a safe protocol for targeted inhibition of hepatic MRP2 is needed to study the intrinsic role of each transporter system. Diltiazem (DTZ) and cyclosporin A (CsA) were first confirmed to be potent MRP2 inhibitors in vitro. Dynamic acquisitions were performed in rats (n = 5–6 per group) to assess the kinetics of [99mTc]mebrofenin in the liver, intestine and heart-blood pool after increasing doses of inhibitors. Their impact on hepatic blood flow was assessed using Doppler ultrasound (n = 4). DTZ (s.c., 10 mg/kg) and low-dose CsA (i.v., 0.01 mg/kg) selectively decreased the transfer of [99mTc]mebrofenin from the liver to the bile (k3). Higher doses of DTZ and CsA did not further decrease k3 but dose-dependently decreased the uptake (k1) and backflux (k2) rate constants between blood and liver. High dose of DTZ (i.v., 3 mg/kg) but not CsA (i.v., 5 mg/kg) significantly decreased the blood flow in the portal vein and hepatic artery. Targeted pharmacological inhibition of hepatic MRP2 activity can be achieved in vivo without impacting OATP activity and liver blood flow. Clinical studies are warranted to validate [99mTc]mebrofenin in combination with low-dose CsA as a novel substrate/inhibitor pair to untangle the role of OATP and MRP2 activity in liver diseases.

scholarly journals Influence of fibrin and liver blood flow on the turnover and the systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator in rabbits

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1493-1497 ◽  
Author(s):  
H Bounameaux ◽  
JM Stassen ◽  
C Seghers ◽  
D Collen
Keyword(s):  
Blood Flow ◽  
Plasminogen Activator ◽  
Human Tissue ◽  
Femoral Vein ◽  
Liver Blood Flow ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Cardiovascular Failure ◽  
Type Plasminogen Activator ◽  
Impaired Liver

Abstract The influence of the presence of fibrin microclots on the systemic fibrinogenolytic effects of intravenous (IV) recombinant human tissue- type plasminogen activator (rt-PA) was studied by injection of a homogenized fibrin suspension in the femoral vein or artery in rabbits. A linear correlation (P less than .001) was found between the extent of fibrinogen breakdown and the amount of fibrin (0 to 32 mg/kg) injected just prior to the IV infusion of rt-PA at a rate of 10 micrograms/kg/min for 60 minutes. This finding suggests that the systemic activation of the fibrinolytic system observed in some patients during infusion of rt-PA may be due, at least in part, to the presence of fibrin in the vascular bed. The effect of blood flow in the liver on the turnover of rt-PA was measured in rabbits after ligation of the hepatic artery and monitoring of the blood flow in the portal vein with a peristaltic pump. The half-life (t1/2) of rt-PA in plasma was inversely correlated with the logarithm of the rate of the liver blood flow. A doubling of the plasma t1/2 of rt-PA was observed after an eightfold reduction of the liver blood flow, suggesting that delayed clearance of rt-PA may occur in patients with severe cardiovascular failure and impaired liver blood flow.

scholarly journals The potential role of the red blood cell in nitrite-dependent regulation of blood flow

2010 ◽  
Vol 89 (3) ◽  
pp. 507-515 ◽  
Author(s):  
Rakesh P. Patel ◽  
Neil Hogg ◽  
Daniel B. Kim-Shapiro
Keyword(s):  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Potential Role

The Potential Role of Adenosine in Regulating Blood Flow in the Eye

1988 ◽  
Vol 4 (1) ◽  
pp. 61-73 ◽  
Author(s):  
SHARON C. BRAUNAGEL ◽  
J.G. XIAO ◽  
GEORGE C.Y. CHIOU
Keyword(s):  
Blood Flow ◽  
Potential Role

Role of ethanol metabolism in the ethanol-induced increase in splanchnic circulation

1986 ◽  
Vol 250 (4) ◽  
pp. G518-G523 ◽  
Author(s):  
J. P. McKaigney ◽  
F. J. Carmichael ◽  
V. Saldivia ◽  
Y. Israel ◽  
H. Orrego
Keyword(s):  
Blood Flow ◽  
Liver Blood Flow ◽  
Portal Blood Flow ◽  
Splanchnic Blood Flow ◽  
Ethanol Metabolism ◽  
Radioactive Microsphere ◽  
Splanchnic Hemodynamics ◽  
Radioactive Microsphere Technique ◽  
Blood Flow Increase

In this study we report the effect on splanchnic hemodynamics of acute oral ethanol at doses ranging from 0.25 to 4.0 g/kg body wt. Flows were determined by use of a radioactive microsphere technique. Ethanol was found to increase portal blood flow by 23-57%. In awake rats this increase reached a plateau at the 0.5 g/kg dose. In ketamine-anesthetized rats, the increase was observed only at doses of 3.0 g/kg or more, with the response at doses of 0.5, 1.0, and 2.0 g/kg being suppressed by ketamine. Inhibition of alcohol dehydrogenase by intra-arterial administration of 4-methylpyrazole resulted in suppression of the liver blood flow increase after ethanol was administered to awake animals. Ethanol in the range of doses studied did not result in changes in blood glucagon levels. Rats fed ethanol-containing diets for 4 wk and withdrawn for 18 h had the same response to acute oral ethanol as did naive rats. It is suggested that ethanol metabolism mediates the effects of ethanol on splanchnic blood flow. An increase in splanchnic blood flow when concurrent with an increase in liver O2 consumption induced by ethanol might protect the liver from hypoxic damage.

scholarly journals The Role of Adenosine in the Vascular Adaptation of Neonatal Cerebral Blood Flow during Hypotension

1991 ◽  
Vol 11 (3) ◽  
pp. 424-431 ◽  
Author(s):  
Nicole Laudignon ◽  
Kay Beharry ◽  
Evangelia Farri ◽  
Jacob V. Aranda
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Adaptive Response ◽  
Receptor Agonist ◽  
Potential Role ◽  
Balloon Catheter ◽  
Cerebral Metabolic Rate ◽  
Important Mediator ◽  
Severe Hypotension

This study investigated the potential role of adenosine in cerebral blood flow (CBF) regulation in the neonate during moderate and severe hypotension. Experiments were done in anesthetized, 1- to 3-day-old piglets. Regional CBF (determined by radiolabeled microsphere technique) and cerebral metabolic rate for O2 (CMRO2) were measured (a) during normotension and (b) during a 3-min period of moderate (58 ± 9 mm Hg) or severe (36 ± 7 mm Hg) hypotension produced by the inflation of a balloon catheter placed in the aortic root. Measurements of CBF and CMRO2 were performed successively after intracerebroventricular (i.c.v.) injections of vehicle (n = 17), the adenosine receptor blocker 8-phenyltheophylline (8–PT, 10 μg, n = 14), and the A2-receptor agonist 5′- N-(ethylcarboxamide)adenosine(NECA, 2 ng, n = 8). After i.c.v. administration of vehicle, none of the parameters studied was significantly altered by moderate hypotension, but severe hypotension decreased the total CBF (mean ± SD) from 86 ± 24 to 40 ± 15 ml min−1 100 g−1 and CMRO2 from 3.2 ± 0.8 to 1.8 ± 1.0 ml min−1 100 g−1 (p < 0.05). Administration of 8-PT did not alter these parameters during normotension, but significantly decreased CBF during moderate hypotension compared to postvehicle values (53 ± 11 versus 81 ± 12 ml min−1 100 g−1, p < 0.05). This loss of autoregulation was completely reversed by NECA. During severe hypotension, 8-PT altered the CBF redistribution towards the brainstem. Mean normotensive CSF concentrations of adenosine (0.76 ± 0.26 μ M) increased during moderate (1.40 ± 1.78 μM) and severe (2.60 ± 2.56 μ M, p < 0.05) hypotension. These data suggest that, in the newborn, adenosine is an important mediator of the cerebral adaptive response to hypotension, even within the range of autoregulation.

Sign in / Sign up

Export Citation Format

Share Document