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Open Access 01-04-2021 | Septicemia | Hepatobiliary-Pancreas

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

Authors: Manil D. Chouhan, Stuart A. Taylor, Alan Bainbridge, Simon Walker-Samuel, Nathan Davies, Steve Halligan, Mark F. Lythgoe, Rajeshwar P. Mookerjee

Published in: European Radiology | Issue 4/2021

Abstract

Objectives

Effects 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.

Methods

Sprague-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.

Results

All 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).

Conclusions

Caval 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 Points

Caval 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.

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Title: Haemodynamic changes in cirrhosis following terlipressin and induction of sepsis—a preclinical study using caval subtraction phase-contrast and cardiac MRI
Authors: Manil D. Chouhan
Stuart A. Taylor
Alan Bainbridge
Simon Walker-Samuel
Nathan Davies
Steve Halligan
Mark F. Lythgoe
Rajeshwar P. Mookerjee
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Keywords: Septicemia
Septicemia
Cardiac MRI
Published in: European Radiology / Issue 4/2021
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-020-07259-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Objectives

Methods

Results

Conclusions

Key Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

Key Points

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