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Journal of Veterinary Internal Medicine 2011Portal hypertension (PH) is the result of increased vascular resistance in the portal circulation, increased portal venous blood flow, or both. In veterinary medicine,... (Review)
Review
Portal hypertension (PH) is the result of increased vascular resistance in the portal circulation, increased portal venous blood flow, or both. In veterinary medicine, where portal pressure is seldom measured directly, the diagnosis of PH often is inferred from identification of associated complications including multiple acquired portosystemic shunts, ascites, and hepatic encephalopathy. Likewise, treatment of PH primarily is aimed at controlling these complications. The goal of this review is to provide an update on the pathophysiology, diagnosis, and treatment of PH. The review draws from information in the veterinary hepatology literature, reviews, and consensus statements in human hepatology and the literature on experimental models of PH.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Hypertension, Portal; Liver; Liver Circulation; Portal System
PubMed: 21382073
DOI: 10.1111/j.1939-1676.2011.00691.x -
Acta Cirurgica Brasileira 2006Liver ischemia has been considered a frequent problem in medical practice, and can be associated to a number of surgical and clinical situations, such as massive hepatic... (Review)
Review
Liver ischemia has been considered a frequent problem in medical practice, and can be associated to a number of surgical and clinical situations, such as massive hepatic resections, sepsis, liver trauma, circulatory shock and liver transplantation. After restoring blood flow, the liver is further subjected to an additional injury more severe than that induced by ischemia. On account of the complexity of mechanisms related to pathophysiology of ischemia and reperfusion (I/R) injury, this review deals with I/R effects on sinusoidal microcirculation, especially when steatosis is present. Alterations in hepatic microcirculation are pointed as a main factor to explain lower tolerance of fatty liver to ischemia-reperfusion insult. The employment of therapeutic strategies that interfere directly with vasoactive mediators (nitric oxide and endothelins) acting on the sinusoidal perfusion seem to be determinant for the protection of the liver parenchyma against I/R. These approaches could be very suitable to take advantage of marginal specimens as fatty livers, in which the microcirculatory disarrangements hamper its employment in liver transplantation.
Topics: Endothelins; Fatty Liver; Humans; Liver; Liver Circulation; Liver Transplantation; Microcirculation; Nitric Oxide; Reperfusion Injury; Vasodilation
PubMed: 17013514
DOI: 10.1590/s0102-86502006000700012 -
Cells Oct 2019Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms.... (Review)
Review
Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology-both are upregulated in patients with advanced liver disease. Endogenous cannabinoids are lipid-signalling molecules derived from arachidonic acid involved in the pathogenesis of cardiovascular dysfunction, portal hypertension, liver fibrosis, and other processes associated with hepatic disease through their interactions with the CB and CB receptors. Apelin is a peptide that participates in cardiovascular and renal functions, inflammation, angiogenesis, and hepatic fibrosis through its interaction with the APJ receptor. The endocannabinoid and apelin systems are two of the multiple cell-signalling pathways involved in the transformation of quiescent hepatic stellate cells into myofibroblast like cells, the main matrix-producing cells in liver fibrosis. The mechanisms underlying the control of hepatic stellate cell activity are coincident despite the marked dissimilarities between the endocannabinoid and apelin signalling pathways. This review discusses the current understanding of the molecular and cellular mechanisms by which the hepatic endocannabinoid and apelin systems play a significant role in the pathophysiology of liver fibrosis.
Topics: Apelin; Carrier Proteins; Endocannabinoids; Enterohepatic Circulation; Fibrosis; Humans; Hypertension, Portal; Inflammation; Liver; Liver Circulation; Liver Cirrhosis; Portal System
PubMed: 31653030
DOI: 10.3390/cells8111311 -
Minerva Anestesiologica Feb 2020This review aimed at summarizing the available evidence on liver transplantation from uncontrolled donation after circulatory death (uDCD) on differences in protocols,... (Review)
Review
This review aimed at summarizing the available evidence on liver transplantation from uncontrolled donation after circulatory death (uDCD) on differences in protocols, donor management, in and ex vivo perfusion techniques from center to center. Uncontrolled DCDs represent a unique, complex model of ischemia-reperfusion injury, so far not completely understood. Nevertheless, results on liver transplantation from uDCDs are promising in terms of long-term graft survival. True difficulties still remain since common/shared protocols are not achievable due to legal differences between countries (i.e. no touch period duration). To date, there is no reliable metrics to determine whether a liver is safe to be ex situ perfused or to be transplanted since existing criteria, as stated by investigators themselves, are so far arbitrary. Values and kinetics of transaminanes during normothermic regional perfusion (nRP) should not considered absolute contraindication at least for ex vivo perfusion. Intraoperative evaluation at organ recovery remains pivotal since macroscopic alterations (i.e. hepatic rupture, an abnormal appearance of gall bladder and choledocus) still represent contraindications for organ retrieval. Concerning ex vivo perfusion, the debate is still open, since the choice of type of machine perfusion (mainly hypothermic vs. normothermic) varies from center to center, mainly relying to the single center experience (especially in controlled DCD), surgeons' believes and/or criteria translated from animal models.
Topics: Death; Graft Survival; Humans; Ischemia; Liver Circulation; Liver Transplantation; Organ Preservation; Shock; Tissue Donors
PubMed: 31334618
DOI: 10.23736/S0375-9393.19.13746-7 -
Journal of Hepatology Apr 2008Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound... (Review)
Review
Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing. Given the importance of these functions it is surprising that relatively little time has been dedicated to studying the precise function and mechanisms of serotonin within the liver. Here we describe what is known about serotonin and the liver and those receptor types that mediate the observed effects with an aim to stimulating new interest in the field of serotonin and liver biology.
Topics: Animals; Humans; Liver; Liver Circulation; Serotonin
PubMed: 18280000
DOI: 10.1016/j.jhep.2008.01.006 -
Hepatology (Baltimore, Md.) Oct 2018Congestive hepatopathy (CH) arises from chronically elevated right-sided heart pressures transmitted to the liver by passive venous congestion. Over time, CH can lead to... (Review)
Review
Congestive hepatopathy (CH) arises from chronically elevated right-sided heart pressures transmitted to the liver by passive venous congestion. Over time, CH can lead to hepatic bridging fibrosis, decompensated cirrhosis, and hepatocellular carcinoma. Currently, there are no evidence-based guidelines to direct appropriate screening or management of patients with CH, partly because of the inability of current clinical tools (serum tests, imaging studies, liver stiffness measurements, and liver biopsy) to accurately estimate hepatic fibrosis or the risk for hepatic decompensation. The Model for End-Stage Liver Disease excluding international normalized ratio (MELD-XI) score is the only validated serum-based test to predict clinical outcomes in CH. Noninvasive liver stiffness measurements are proving to be of minimal utility as all patients with CH have elevated values that currently cannot differentiate between congestion and fibrosis. In addition, fibrosis staging by liver biopsy is difficult to standardize because of heterogeneous collagen deposition in CH. Moreover, liver biopsy results have little predictive value for post-heart transplant hepatic outcomes in patients with CH. Evaluating liver nodules and masses is also complicated in CH as the finding of delayed venous washout in nodules is not specific for hepatocellular carcinoma in the background of a congested liver, and these lesions may require biopsy to confirm the diagnosis. The lack of effective clinical tools for predicting liver fibrosis and liver function suggests the need for the development of novel biomarkers in patients with CH to assist in the management of this complicated disease. (Hepatology 2018; 00:000-000).
Topics: Biomarkers; Biopsy, Needle; Disease Progression; Elasticity Imaging Techniques; Female; Humans; Immunohistochemistry; Liver Circulation; Liver Cirrhosis; Liver Failure; Male; Risk Assessment; Vascular Diseases
PubMed: 29672883
DOI: 10.1002/hep.30048 -
PloS One 2022Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life.
MATERIAL AND METHODS
This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics.
RESULTS
There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44-0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population.
CONCLUSION
Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.
Topics: Adult; Double-Blind Method; Female; Fetus; Humans; Liver Circulation; Metformin; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications
PubMed: 35089960
DOI: 10.1371/journal.pone.0262987 -
Annals of Hepatology 2016In patients with advanced liver disease with portal hypertension, portal-systemic collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage, hepatic... (Review)
Review
In patients with advanced liver disease with portal hypertension, portal-systemic collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage, hepatic encephalopathy, ascites, hepatopulmonary syndrome and portopulmonary hypertension. Angiogenesis has a pivotal role in the formation of portal-systemic shunts. Recent research has defined many of the mediators and mechanisms involved in this angiogenic process, linking the central roles of hepatic stellate cells and endothelial cells. Studies of animal models have demonstrated the potential therapeutic impact of drugs to inhibit angiogenesis in cirrhosis. For example, inhibition of VEGF reduces portal pressure, hyperdynamic splanchnic circulation, portosystemic collateralization and liver fibrosis. An improved understanding of the role of other angiogenic factors provides hope for a novel targeted therapy for portal hypertension with a tolerable adverse effect profile.
Topics: Angiogenesis Inhibitors; Angiogenic Proteins; Animals; Collateral Circulation; Disease Models, Animal; Humans; Hypertension, Portal; Liver Circulation; Neovascularization, Pathologic; Portal System; Severity of Illness Index; Signal Transduction
PubMed: 27049484
DOI: 10.5604/16652681.1198799 -
Updates in Surgery Sep 2023Post-resective liver failure is a frequent complication of liver surgery and it is due to portal hyperperfusion of the remnant liver and to arterial vasoconstriction, as...
Post-resective liver failure is a frequent complication of liver surgery and it is due to portal hyperperfusion of the remnant liver and to arterial vasoconstriction, as buffer response of the hepatic artery. In this context, splenectomy allows a reduction of portal flow and increases the survival chance in preclinical models. SerpinB3 is over-expressed in the liver in oxidative stress conditions, as a mechanism of cell defense to provide survival by apoptosis inhibition and cell proliferation. In this study, the expression of SerpinB3 was assessed as predictor of liver damage in in vivo models of major hepatic resection with or without splenectomy. Wistar male rats were divided into 4 groups: group A received 30% hepatic resection, group B > 60% resection, group C > 60% resection with splenectomy and group D sham-operated. Before and after surgery liver function tests, echo Doppler ultrasound and gene expression were assessed. Transaminase values and ammonium were significantly higher in groups that underwent major hepatic resection. Echo Doppler ultrasound showed the highest portal flow and resistance of the hepatic artery in the group with > 60% hepatectomy without splenectomy, while the association of splenectomy determined no increase in portal flow and hepatic artery resistance. Only the group of rats without splenectomy showed higher shear-stress conditions, reflected by higher levels of HO-1, Nox1 and of Serpinb3, the latter associated with an increase of IL-6. In conclusion, splenectomy controls inflammation and oxidative damage, preventing the expression of Serpinb3. Therefore, SerpinB3 can be considered as a marker of post-resective shear stress.
Topics: Male; Rats; Animals; Rats, Wistar; Liver Circulation; Liver; Hepatectomy; Hepatic Artery; Splenectomy
PubMed: 37204659
DOI: 10.1007/s13304-023-01531-6 -
American Journal of Physiology. Heart... Jan 2014Each regional circulation has unique requirements for blood flow and thus unique mechanisms by which it is regulated. In this review we consider the role of smooth... (Review)
Review
Each regional circulation has unique requirements for blood flow and thus unique mechanisms by which it is regulated. In this review we consider the role of smooth muscle contractile diversity in determining the unique properties of selected regional circulations and its potential influence on drug targeting in disease. Functionally smooth muscle diversity can be dichotomized into fast versus slow contractile gene programs, giving rise to phasic versus tonic smooth muscle phenotypes, respectively. Large conduit vessel smooth muscle is of the tonic phenotype; in contrast, there is great smooth muscle contractile diversity in the other parts of the vascular system. In the renal circulation, afferent and efferent arterioles are arranged in series and determine glomerular filtration rate. The afferent arteriole has features of phasic smooth muscle, whereas the efferent arteriole has features of tonic smooth muscle. In the splanchnic circulation, the portal vein and hepatic artery are arranged in parallel and supply blood for detoxification and metabolism to the liver. Unique features of this circulation include the hepatic-arterial buffer response to regulate blood flow and the phasic contractile properties of the portal vein. Unique features of the pulmonary circulation include the low vascular resistance and hypoxic pulmonary vasoconstriction, the latter attribute inherent to the smooth muscle cells but the mechanism uncertain. We consider how these unique properties may allow for selective drug targeting of regional circulations for therapeutic benefit and point out gaps in our knowledge and areas in need of further investigation.
Topics: Animals; Humans; Liver Circulation; Muscle Contraction; Muscle, Smooth, Vascular; Pulmonary Circulation; Renal Circulation
PubMed: 24186099
DOI: 10.1152/ajpheart.00493.2013