Hepatic Arterial Buffer Response Research Articles

Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

Monochorionic twins (MC) have higher risk ofperinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was-0.16 (±0.97). Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

Enlargement of the hepatic artery is present in dogs with a congenital extrahepatic portosystemic shunt and is independent of shunt insertion into the systemic circulation.

The accurate diagnosis of portovascular anomalies has been facilitated by improvements in diagnostic imaging technology. In humans, hepatic arterial blood flow changes in response to the reduction in portal blood flow. The hepatic arterial buffer response characterizes an intrinsic regulatory mechanism in response to reduced portal venous blood flow, which results in hepatic arterial enlargement. At the authors' institution, enlargement of the hepatic artery has been anecdotally observed in a population of dogs with extrahepatic portosystemic shunting, consistent with previous literature that documents variability in hepatic arterial size. In this retrospective, blinded, analytical study, a hepatic artery:aorta (Ha:Ao) ratio was assessed on CT studies from 112 dogs, with (n=43) and without (n=69) an extrahepatic congenital portosystemic shunt in order to compare the hepatic artery size independent of body weight between the two populations. A significant increase in the Ha:Ao ratio was documented in dogs with an extrahepatic portosystemic shunt (EHPSS) compared with those dogs with no EHPSS independent of the location of shunt insertion into the systemic circulation (P<.001). Three cases had repeat CT after surgery, and all had Ha:Ao ratio reductions following treatment. The authors propose that this may be an additional imaging feature observed in dogs with an EHPSS.

The Portal Vein: A Comprehensive Review.

Radiologists are familiar with the appearances of a normal portal vein; variations in its anatomy are commonplace and require careful consideration due to the implications for surgery. These alterations in portal vein anatomy have characteristic appearances that are clearly depicted on CT, MR, and US images. Similarly, there are numerous congenital and acquired disorders of the portal vein that are deleterious to its function and can be diagnosed by using imaging alone. Some of these conditions have subtle imaging features, and some are conspicuous at imaging but poorly understood or underrecognized. The authors examine imaging appearances of the portal vein, first by outlining the classic and variant anatomy and then by describing each of the disorders that impact portal vein function. The imaging appearances of portal vein abnormalities discussed in this review include (a) occlusion from and differentiation between bland thrombus and tumor in vein and the changes associated with resultant hepatic artery buffer response changes, cavernous transformation of the portal vein, and portal biliopathy; (b) ascending thrombophlebitis of the portal vein (pylephlebitis); (c) portal hypertension and its causes and sequelae; (d) the newly described disease entity portosinusoidal vascular disorder; and (e) intra- and extrahepatic shunts of the portal system, both congenital and acquired (including Abernethy malformations), and the associated risks. Current understanding of the pathophysiologic processes of each of these disorders is considered to aid the approach to reporting. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Hepatic arterial buffer response: activation in donor fetuses and the effect of laser ablation of intertwin anastomosis.

Hepatic arterial buffer response (HABR) is an important defence mechanism for maintaining liver blood flow. It is suspected that HABR is active in monochorionic diamniotic twins (MCDA) with twin-to-twin transfusion syndrome (TTTS) where donor compensates a setting of volume depletion and the recipient an overload. The present study investigates whether in TTTS, HABR is active in donor and/or recipient individually and try to determine if the activation of HABR is a direct response to TTTS. Hepatic artery (HA) peak systolic velocity (PSV) was measured in normal MCDA fetuses and TTTS. Correlation with relevant fetal Dopplers and characteristics were determined. Z-scores for HA-PSV (HAV-Z) were calculated and its association with TTTS in donors and recipients were determined as well as changes in HAV-Z after laser treatment. In this study 118 MCDA were included, 61.9 % normal and 38.1 % TTTS. Of the TTTS 22 required laser treatment. A total of 382 scans were performed in normal group and 155 in TTTS. Our data demonstrates that in donors HAV-Z was 2.4 Z-scores higher compared to normal fetuses (β=2.429 95 % CI 1.887, 2.971; p<0.001) and after laser treatment HAV-Z reduced (β=-1.829 95 % CI-2.593,-1.064; p<0.001). There was no significant difference between recipients and normal (β=-0.092 95 % CI-0.633, 0.449; p=0.738). HABR is active in TTTS, promoting an increased hepatic blood flow in donors. The activation is direct response to TTTS as shown by the reduction in HAV-Z after laser. This finding provides important insights into the pathophysiology of TTTS.

Hepatic Arterial Buffer Response in Liver Transplant Recipients: Implications and Treatment Options.

The liver blood supply portrays one of the most sophisticated archetypes of circulation. Despite its weight (representing only 2.5% of body weight), the liver receives 25% of the cardiac output, allowing the hepatic parenchyma to be the most richly perfused of any organ. The anatomical distinctiveness of the double afferent blood supply is established between the hepatic artery and the portal vein, ensuring a total blood flow of 100 to 130 mL/min per 100 g of liver. Approximately 20 to 25% of the blood perfusing the liver is well oxygenated, and is provided by the hepatic artery. In addition to hepatic parenchymal cells, the hepatic artery provides the exclusive blood supply to the intrahepatic bile ducts. The portal vein, formed by the confluence of the splenic vein, mesenteric veins, gastric veins, and pancreatic vein, supplies around 75 to 80% of the afferent blood, which is partially deoxygenated.[1] [2] Mixing of arterial and portal blood occurs in the sinusoids, an exclusive, dynamic microvascular structure that serves as the principal site of exchange between the blood and the perisinusoidal space.[3] The hepatic veins (typically three—right, middle, and left) drain the blood from those locations into the inferior vena cava.

Hepatic arterial buffer response in monochorionic diamniotic pregnancies with twin-to-twin transfusion syndrome.

Hepatic arterial buffer response (HABR) is animportant regulatory process for hepatic blood flow. Itsactivity has been described in some fetal adverse conditions but in twin-to-twin transfusion syndrome (TTTS) it is unknown if such response is present. The aim of this study is to test the hypothesis that HABR operates in monochorionic diamniotic twins (MCDA) with TTTS. Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured prospectively in 64 MCDA pregnancies. 43 without TTTS (group 1) and in 21 pregnancies with TTTS (group 2). We calculated ratios for PI (HAPI-ratio) and PSV (HAV-ratio) between recipient and donor in group 2 or bigger and smaller fetus in group 1 and compared groups. The association of HAV-ratio and HAPI ratio with TTTS, relation with other fetal Dopplers and reliability of measurement by a single operator were investigated. HAV-ratio and HAPI-ratio appears to be independent from fetal Dopplers, estimated weight and gestational age. In group 2, HAV-ratio is lower than group 1 (p<0.001, 95% CI 0.443-0.643). In group 1 the mean HAV-ratio is 1.014 (±0.021) while in group 2 is 0.47 (±0.035). HAPI-ratio is lower in group 2 than in group 1 although this difference was not significant (p=0.066, 95% CI-0.007-0.231). A good reliability of measurements of hepatic artery PSV and PI was demonstrated by intraclass correlation coefficient analysis (ICC 0.971 95% CI 0.963-0.977, p<0.001 and ICC 0.694 95% CI 0.596-0.772, p<0.001, respectively). Monochorionic pregnancies with TTTS are associated with lower HAV-ratios. This could be explained by an active HABR.

Assessment of liver blood flow regulation mechanism by ultrasound

The constancy of hepatic blood flow is important for several homeostatic roles. This paper reviews studies related to liver blood flow regulation mechanism. The liver has mechanism maintain a constant hepatic blood flow and compensate for portal flow changes. A reduction in portal flow leads to reduced intrahepatic distending pressure, resulting the hepatic arterial buffer response causes dilation of the hepatic artery, thus buffering the Portal flow change. This mechanism is exclusive to this specific vascular bed and offer a great illustration of multiple integrative regulation of a significant homeostatic organ. Ultrasound provides noninvasive accurate information on the liver hemodynamic and assess the flow in the hepatic artery and the portal vein specially diameter of vessels. Aim: The aim of this study was to evaluate the dual hepatic blood supply in normal individual and compared altered in the hepatic artery buffer response with chronic hepatic diseases. Materials and methods: The current review focuses on researches that evaluate the mechanisms involved in maintaining a steady hepatic arterial buffer response (HBF), such as the impact of portal blood flow on hepatic artery flow, or assessing the intrinsic regulation of hepatic arterial blood flow by measure the hepatic arterial buffer response intraoperative in patients with or without cirrhosis using an ultrasound transit-time flowmetry, or by duplex ultrasound, Moreover studies to understand the role of hepatic flow in liver atrophy.

The effect of obeticholic acid on hepatic blood flow in isolated, perfused porcine liver: Correction of oxygen‐nutrient mismatch might be a putative mechanism of action in NASH

AbstractBackgroundThe liver has a unique dual blood supply. Chronic excess nutrient delivery via the portal vein (PV), unmatched by hepatic artery (HA) oxygen could account for liver damage in NASH. Obeticholic acid (OCA), is a Farnesoid‐X‐receptor agonist with vascular targets in the liver. It has shown efficacy in NASH treatment. We hypothesized that increased oxygen delivery via HA vasodilatation, coupled with a reflex reduction in PV and nutrient flow due to the HA buffer response (HABR), could account for the therapeutic benefit in NASH.AimWe studied the direct effects of OCA on HA, PV and hepatic vein (HV) blood flow in an isolated, pump perfused porcine liver model.MethodsSix porcine livers (two controls) were perfused ex vivo with phosphate buffered saline (PBS), using a unique cardio‐emulation pump for the HA. OCA in solution with methyl cellulose, 0 mg/kg liver weight, followed by 0.14, 0.28, 0.56 and 1.12 mg/kg, was injected at 30‐min intervals, directly into the PV. Controls were perfused with PBS only.ResultsHA blood pressure, perfusate pH, perfusate dissolved oxygen (DO) and temperature remained relatively constant throughout. HA flow increased dose‐responsively up to 9.9 ± 8.9 per cent. Conversely, PV flow fell, up to −19 ± 16 per cent. HV flow rose and stabilized at 11 ± 11.8 per cent after the first dose. Control livers (n = 2) showed minor changes only.ConclusionOCA directly increased HA inflow, simultaneously decreasing PV flow, consistent with the hepatic artery buffer response, HABR. Increased oxygenation via the HA coupled with a reduction in nutrients via PV provides a rational concept for the etiology of NASH and the therapeutic benefit of OCA.

Hyperspectral evaluation of liver oxygenation in a murine model of metabolic associated liver disease and hepatocellular carcinoma

Abstract Objective Untreated MAFLD is a continuum of disease ranging from hepatic steatosis to cirrhosis and hepatocellular carcinoma (HCC). Throughout the disease progression, a change in hepatic hemodynamics occurs as portal hypertension. Hepatic arterial buffer response is a compensatory mechanism to maintain liver perfusion facing reduction of portal flow. These changes could also impair hepatic oxygenation homeostasis. The aim of this study is to test this hypothesis in mouse models and to shed light on the oxygenation of fatty, portal hypertensive liver and its impact on HCC carcinogenesis. Methods C57BL/6 mice were fed a HFD starting from 4 weeks of age, porto-systemic shunts (or sham) were created at 8 weeks, and monitored up to 40 weeks. ND-fed non-shunted mice were used as control group. Hyperspectral imaging (HSI) was utilized to quantify tissue oxygenation (StO2) of ND, HFD and HFD-shunted mice. In a second set of experiment, we explored the role of a common hepatic artery ligation in the studied DEN-induced HFD mouse model. Results HFD induced hepatic steatosis and portal pressure compared to ND. Porto-systemic shunt could deviate about 67% of the portal flow through the spleen to the systemic circulation, thus reducing portal pressure close-to-normal levels. Compared to control mice, HFD feeding increased liver oxygenation (p=0.0004), while shunting restored a close to normal level (p&amp;lt;0.001). The oxygenation of small bowel is decreased in a similar manner in both HFD and HFD-shunted mice. In HFD-fed mice, artery ligation led to less carcinogenesis compared to mice without artery ligation (p=0.026). In addition, artery ligation was also associated with smaller HCCs (p=0.027). Conclusion Early stages of MAFLD alter hepatic oxygen homeostasis. Fatty liver, when associated to portal hypertension, express higher liver oxygenation levels, compared to control group. This could due to hepatocyte ballooning with a narrowing of portal system, thus bring portal hypertension state with a simultaneous arterial buffer response. Additionally, small bowel of portal hypertensive mice showed lower oxygen levels mirroring an intestinal venous congestion typical of portal hypertension. Oxygen deprivation, through artery ligation, decreases HCC carcinogenesis and reduces HCC nodules volume. Yet further research is needed but oxygen homeostasis seems play a role in MAFLD progression as well in HCC pathophysiology.

Preliminary Results of Hepatic Blood Flow Modulation in an Experimental Model of Hepatectomy – Implications for Hepatic Artery Buffer Response Modulation

Introduction: Portal hyperperfusion of the remnant liver has been implicated in post hepatectomy liver failure (PHLF) following major hepatectomy by inducing arterial vasoconstriction, also called Hepatic Artery Buffer Response (HABR). We aimed to compare the effect of a selective A2Aadenosine receptor agonist Regadenoson to a porto-caval (P-C) shunt in an experimental model of hepatectomy in piglets on hepatic blood flow modulation. Methods: A cohort study with cross-over design of serial doppler measurements in landrace pigs weighing 25-30 Kg was performed; all subjects underwent laparotomy and baseline measurements were taken. Thereafter extended left hepatectomy with P-C shunt was performed and measurements were repeated. Finally, the P-C shunt was occluded and all animals were administered intra-arterially 400mcg of regadenoson, prior repeating measurements. Results: The baseline portal vein and hepatic artery flow were 28.5 ± 7.47 ml/sec and 118.66 ± 19.28 ml/sec respectively. After hepatectomy a significant increase of the portal vein flow by 91.8% while the hepatic artery flow increase only by 26.4%, signifying activation of the HABR. Opening of the P-C shunt decreased the portal vein flow by 24.69% and a more pronounced decrease of hepatic artery flow (34.22%). After occlusion of the portocaval shunt and administration of regadenoson there was a minor decrease of the portal flow by 13.71% while there was a significant drop of the hepatic artery flow by 55.33%, thus more effectively decreasing arterial vasoconstriction (p<0.005). Conclusion: Regadenoson can more effectively decrease hepatic artery flow than PC shunt, thus signifying a potential role in the management of PHLF.

Ultrasound Demonstration of Hepatic Arterial Buffer Response for Blood Flow Regulation

This is observation analytical case control study deal with assessment of hepatic arterial buffer response for blood flow regulation using ultrasonography taking 300 subjects. 150 normal control group and 150 patients with chronic liver diseases. Several previous studies in various setting has support ultrasound scanning as non-invasive, cost effected, reliable, and accurate tool for measuring portal vein diameter and flow comparing with hepatic artery diameter for assess hepatic artery buffer response for blood flow regulation in chronic liver diseases. The Aim: Importance of the study to help in diagnosis impairment of HABR for blood flow regulation in chronic liver diseases in early stage to avoid the complication. As well as to reduce the cost and time of other examination. Method: The data was collected, analyzed by using Statistical Packaged for Social Studies (SPSS). Ultrasound examinations were performed in Tropical Diseases Teaching Hospital. Omdurman, Khartoum State during the period) from January 2021to August 2022(on 150 patients as study group (85 male and 65 female) and 150 control group with normal abdominal scan (Patient who had previous abdominal surgery was excluded). The Result: In result we found significant correlation (P=0.00) between hepatic artery diameter, liver craniocaudal length CCL\cm, caudate lobe size and portal vein diameter, with direction of flow. Highly significant correlation (r=-0.222; P=0.006) was noticed between portal vein diameter and hepatic artery diameter of patient under investigation. In patient with cirrhosis found dilated portal vein associated with Hepatofugal flow away from liver combined with dilated hepatic artery to compensate the liver supply. In case of fatty liver infiltration, the portal vein decrease diameter and flow associated with increase liver size and hepatic artery diameter to supply the liver. In liver tumor HCC the portal vein decrease diameter and flow associated with increase liver size and hepatic artery diameter. In hepatitis both portal vein and hepatic artery dilated to increase supply to the liver. These were expected and goes with previous study. The study also found that there was significant correlation between Sudanese HABR and international standard. The study recommended further study to measure HABR routinely with chronic liver diseases ultrasound scan

Hepatic pseudolesions caused by alterations in intrahepatic hemodynamics

Hepatic pseudolesion may occur in contrast-enhanced computed tomography and magnetic resonance imaging due to the unique haemodynamic characteristics of the liver. The concept of hepatic arterial buffer response (HABR) has become mainstream for the understanding of the mechanism of the reciprocal effect between hepatic arterial and portal venous flow. And HABR is thought to be significantly related to the occurrence of the abnormal imaging findings on arterial phase of contrast enhanced images, such as hepatic arterial-portal vein shunt and transient hepatic attenuation difference, which mimic hypervascular tumor and may cause clinical problems. Third inflow to the liver also cause hepatic pseudolesion, and some of the cases may show histopathologic change such as focal hyperplasia, focal fatty liver, and focal sparing of fatty liver, and called pseudotumor. To understand these phenomena might be valuable for interpreting the liver imaging findings.

Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy.

Simple SummaryRadioembolization of hepatic tumors is performed by injecting 90Y or 166Ho loaded spheres into the hepatic artery. A twofold tumor to normal liver absorbed dose ratio is commonly obtained. In order to improve tumoral cell killing while preserving lobule function, co-injection of arterial vasoconstrictor has been proposed, but without success: the hepatic arterial buffer response quickly inhibits the arterioles vasoconstriction. The aim of the study is to investigate whether it is possible to take benefit from this buffer response, by co-infusing a mesenteric arterial vasodilator in order to dump the hepatic lobules arterial flow. Animal studies evidencing such mechanism are reviewed. Some potential mesenteric vasodilators are identified and their safety profile discussed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in hepatocellular carcinoma (HCC), more frequent in obese subjects, and where ultra-selective spheres delivery is often not possible.Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.

Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification.

Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray's Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.

Haemodynamic changes in cirrhosis following terlipressin and induction of sepsis\u2014a preclinical study using caval subtraction phase-contrast and cardiac MRI

ObjectivesEffects of liver disease on portal venous (PV), hepatic arterial (HA), total liver blood flow (TLBF), and cardiac function are poorly understood. Terlipressin modulates PV flow but effects on HA, TLBF, and sepsis/acute-on-chronic liver failure (ACLF)-induced haemodynamic changes are poorly characterised. In this study, we investigated the effects of terlipressin and sepsis/ACLF on hepatic haemodynamics and cardiac function in a rodent cirrhosis model using caval subtraction phase-contrast (PC) MRI and cardiac cine MRI.MethodsSprague-Dawley rats (n = 18 bile duct–ligated (BDL), n = 16 sham surgery controls) underwent caval subtraction PCMRI to estimate TLBF and HA flow and short-axis cardiac cine MRI for systolic function at baseline, following terlipressin and lipopolysaccharide (LPS) infusion, to model ACLF.ResultsAll baseline hepatic haemodynamic/cardiac systolic function parameters (except heart rate and LV mass) were significantly different in BDL rats. Following terlipressin, baseline PV flow (sham 181.4 ± 12.1 ml/min/100 g; BDL 68.5 ± 10.1 ml/min/100 g) reduced (sham − 90.3 ± 11.1 ml/min/100 g, p < 0.0001; BDL − 31.0 ± 8.0 ml/min/100 g, p = 0.02), sham baseline HA flow (33.0 ± 11.3 ml/min/100 g) increased (+ 92.8 ± 21.3 ml/min/100 g, p = 0.0003), but BDL baseline HA flow (83.8 ml/min/100 g) decreased (− 34.4 ± 7.5 ml/min/100 g, p = 0.11). Sham baseline TLBF (214.3 ± 16.7 ml/min/100 g) was maintained (+ 2.5 ± 14.0 ml/min/100 g, p > 0.99) but BDL baseline TLBF (152.3 ± 18.7 ml/min/100 g) declined (− 65.5 ± 8.5 ml/min/100 g, p = 0.0004). Following LPS, there were significant differences between cohort and change in HA fraction (p = 0.03) and TLBF (p = 0.01) with BDL baseline HA fraction (46.2 ± 4.6%) reducing (− 20.9 ± 7.5%, p = 0.03) but sham baseline HA fraction (38.2 ± 2.0%) remaining unchanged (+ 2.9 ± 6.1%, p > 0.99). Animal cohort and change in systolic function interactions were significant only for heart rate (p = 0.01) and end-diastolic volume (p = 0.03).ConclusionsCaval subtraction PCMRI and cardiac MRI in a rodent model of cirrhosis demonstrate significant baseline hepatic haemodynamic/cardiac differences, failure of the HA buffer response post-terlipressin and an altered HA fraction response in sepsis, informing potential translation to ACLF patients.Key PointsCaval subtraction phase-contrast and cardiac MRI demonstrate:• Significant differences between cirrhotic/non-cirrhotic rodent hepatic blood flow and cardiac systolic function at baseline.• Failure of the hepatic arterial buffer response in cirrhotic rodents in response to terlipressin.• Reductions in hepatic arterial flow fraction in the setting of acute-on-chronic liver failure.

Stimulation of the hepatic arterial buffer response using exogenous adenosine: hepatic rest/stress perfusion imaging.

The hepatic arterial buffer response is a mechanism mediated by adenosine whereby hepatic arterial perfusion (HAP) increases when portal flow decreases, and is implicated in liver disease. The first study aim was to measure HAP in patients undergoing myocardial perfusion imaging (MPI), thus developing hepatic arterial rest/stress perfusion imaging (HAPI). The second aim was to compare adenosine-induced changes in splenic perfusion (SP) and HAP with corresponding changes in myocardial blood flow (MBF). Patients had MPI with 82Rb PET/CT using adenosine (n = 45) or regadenoson (n = 33) for stressing. SP and HAP were measured using a first-pass technique that gives HAP rather than total hepatic perfusion. Renal perfusion (RP) was also measured. Mean MBF and HAP increased after both adenosine ([stress-rest]/rest 1.1 and 0.8) and regadenoson (1.4 and 0.6), but the respective changes did not correlate. After adenosine, SP (- 0.48) and RP (- 0.26) both decreased. The change in SP correlated positively with the change in MBF (r = 0.36; p = 0.015) but did not correlate with change in HAP. After regadenoson, SP (0.2) and RP (0.2) both increased. The changes in SP correlated with the changes in MBF (r = 0.39; p = 0.025) and HAP (r = 0.39; p = 0.02). Changes in RP correlated with changes in HAP (r = 0.51; p = 0.0008) but not MBF. Resting SP (r = 0.32; p = 0.004), but not resting HAP, correlated with hepatic fat burden. Adenosine-induced change in HAP also correlated with hepatic fat (r = 0.29; p = 0.05). HAPI could be a useful new hepatic function test. Neither splenic 'switch-off' nor hepatic arterial 'switch-on' identifies adequacy of stress in MPI. • This article describes a new method for assessing arterial perfusion of the liver and its capacity to respond to an infusion of adenosine, a substance that normally 'drives' hepatic arterial flow. • Hepatic arterial flow increased in response to adenosine, sometimes dramatically. Adenosine is already used clinically to stimulate myocardial blood flow in patients with suspected coronary disease, but the increase in flow did not correlate with the corresponding increase in hepatic arterial flow. • Analogous to the use of adenosine in the myocardium, the increase in hepatic arterial flow in response to adenosine has the potential to be a new clinically useful method for the evaluation of hepatic arterial haemodynamics in liver disease.

Hypoxia and oxidative stress: The role of the anaerobic gut, the hepatic arterial buffer response and other defence mechanisms of the liver

Hypoxia and oxidative stress: The role of the anaerobic gut, the hepatic arterial buffer response and other defence mechanisms of the liver

Computational simulations for the hepatic arterial buffer response after liver graft transplantation from an adult to a child

Live donor liver transplantation (LDLT) is an important surgical technique for treating children with end-stage liver diseases. Surgical complications may occur, e.g., due to thrombosis formed in hepatic arteries (HAs) or portal veins (PVs). From the hepatic circulation point of view, a hepatic arterial buffer response (HABR) mechanism, where the HA flow counteracts the changes in the PV flow, could play a role in graft dysfunction, yet this intricate mechanism has not been elucidated in LDLT procedures. In this short communication we simulate the HABR which may occur in an adult-to-child LDLT, where the left lateral lobe of an adult donor is transplanted to a child. Using an electrical analog model we show that the HABR could be triggered in both portal hyper-perfusion and venous obstruction scenarios, and this may be associated with arterial and/or venous thrombosis in the liver graft as reported in clinical studies. In conclusion, HABR could be important in adult-to-child LDLT and it should be considered in pre-surgical planning.

Portal hyperperfusion after major liver resection and associated sinusoidal damage is a therapeutic target to protect the remnant liver.

Extended liver resection results in loss of a large fraction of the hepatic vascular bed, thereby causing abrupt alterations in perfusion of the remnant liver. Mechanisms of hemodynamic adaptation and associated changes in oxygen metabolism after liver resection and the effect of mechanical portal blood flow reduction were assessed. A pig model (n = 16) of extended partial hepatectomy was established that included continuous observation for 24 h under general anesthesia. Pigs were randomly separated into two groups, one with a portal flow reduction of 70% compared with preoperative values, and the other as a control (n = 8, each). In controls, portal flow [mean (SD)] increased from 74 (8) mL·min-1·100 g-1 preoperatively to 240 (48) mL·min-1·100 g-1 at 6 h after resection (P < 0.001). Hepatic arterial buffer response was abolished after resection. Oxygen uptake per unit liver mass increased from 4.0 (1.1) mL·min-1·100 g-1 preoperatively to 7.7 (1.7) mL·min-1·100 g-1 8 h after resection (P = 0.004). Despite this increase in relative oxygen uptake, total hepatic oxygen consumption (V̇o2) was not maintained, and markers of hypoxia and anaerobic metabolism were significantly increased in hepatocytes after resection. Reduced postoperative portal flow was associated with significantly decreased levels of aspartate aminotransferase and bilirubin and increased hepatic clearance of indocyanine green. In conclusion, major liver resection was associated with persistent portal hyperperfusion, loss of the hepatic arterial buffer response, decreased total hepatic V̇o2 and with increased anaerobic metabolism. Portal flow modulation by partial portal vein occlusion attenuated liver injury after extended liver resection.NEW & NOTEWORTHY Because of continuous monitoring, the experiments allow precise observation of the influence of liver resection on systemic and local abdominal hemodynamic alterations and oxygen metabolism. Major liver resection is associated with significant and persistent portal hyperperfusion and loss of hepatic arterial buffer response. The correlation of portal hyperperfusion and parameters of liver injury and dysfunction offers a novel therapeutic option to attenuate liver injury after extended liver resection.

Model Assisted Analysis of the Hepatic Arterial Buffer Response During Ex Vivo Porcine Liver Perfusion.

The hepatic arterial buffer response is a well-known phenomenon in hepatic circulation, describing the response of hepatic arterial resistance to changes in portal vein flow. Several vasoactive metabolites underlying its mechanism have been proposed, however, there is currently no clear consensus. The aim of this study is to investigate the hepatic arterial buffer response of porcine livers preserved in a controlled ex vivo perfusion machine. Porcine livers are perfused on an ex vivo perfusion machine and hemodynamic experiments investigating the hepatic arterial resistance response to portal vein flow and vena cava pressure variations are conducted. A simple hemodynamic model is developed to support the interpretation of the received measurements. Further, a mechanism is proposed that explains hepatic arterial resistance changes in response to vena cava pressure as myogenic and in response to portal vein flow as a combined washout and myogenic effect. A clear correlation between hepatic sinusoidal pressure levels and hepatic arterial resistance is observed where an increase of approximately 4mmHg of hepatic sinusoidal pressure level results in doubling of the hepatic arterial resistance. This relation is considered during the analysis of the portal vein flow variations resulting in a reduced isolated effect of adenosine washout on hepatic arterial resistance. With an average buffer capacity of 27% during our experiments, the hepatic arterial buffer response shows to be unimpaired in the ex vivo scenario. First, washout and myogenic effects both influence the hepatic arterial buffer response; and second, hepatic sinusoidal pressure levels strongly influence the hepatic arterial resistance. These results present new findings in hemodynamics of the liver, which are fundamental for successful ex vivo liver perfusion.