The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig

Author:

Hammond John S.12,Godtliebsen Fred3,Steigen Sonja45,Guha I. Neil1,Wyatt Judy6,Revhaug Arthur78,Lobo Dileep N.19ORCID,Mortensen Kim E.78

Affiliation:

1. Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen’s Medical Centre, Nottingham, U.K.

2. Department of Hepato-Pancreatico-Biliary Surgery and Transplantation, Freeman Hospital, Newcastle upon Tyne, U.K.

3. Department of Mathematics and Statistics, UiT – The Arctic University of Norway, Tromsø, Norway

4. Institute of Medical Biology, UiT – The Arctic University of Norway, Tromsø, Norway

5. Department of Clinical Pathology, The University Hospital of North Norway, Tromsø, Norway

6. Department of Pathology, Leeds Teaching Hospitals NHS Trust, Leeds, U.K.

7. Surgical Research Laboratory, Institute of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway

8. Department of Gastrointestinal Surgery, The University Hospital of North Norway, Tromsø, Norway

9. MRC/ARUK Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, U.K.

Abstract

Abstract Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis, and when PVP is reduced, rates of liver dysfunction decrease. The aim of the present study was to characterize the hemodynamic, biochemical, and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects. Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5–1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80% hepatectomy, and were maintained under terminal anesthesia for 8 h. The primary outcome was changed in PVP. Secondary outcomes included portal venous flow (PVF), hepatic arterial flow (HAF), and biochemical and histological markers of liver injury. Hepatectomy increased PVP (9.3 ± 0.4 mmHg pre-hepatectomy compared with 13.0 ± 0.8 mmHg post-hepatectomy, P<0.0001) and PVF/g liver (1.2 ± 0.2 compared with 6.0 ± 0.6 ml/min/g, P<0.0001) and decreased HAF (70.8 ± 5.0 compared with 41.8 ± 5.7 ml/min, P=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4 ± 0.8 mmHg, P=0.046 and PCS = 8.3 ± 1.2 mmHg, P=0.025) and PVF (control = 869.0 ± 36.1 ml/min compared with terlipressin = 565.6 ± 25.7 ml/min, P<0.0001 and PCS = 488.4 ± 106.4 ml/min, P=0.002) compared with control. Treatment with terlipressin increased HAF (73.2 ± 11.3 ml/min) compared with control (40.3 ± 6.3 ml/min, P=0.026). The results of the present study suggest that terlipressin and PCS may have a role in the prevention and treatment of post-resection liver failure.

Publisher

Portland Press Ltd.

Subject

General Medicine

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