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

Hammond, John S.; Godtliebsen, Fred; Steigen, Sonja; Guha, I. Neil; Wyatt, Judy; Revhaug, Arthur; Lobo, Dileep N.; Mortensen, Kim E.

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 this 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 hours. The primary outcome was change 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±0.4mm Hg pre-hepatectomy vs.13.0±0.8mm Hg post-hepatectomy, p less than 0.0001) and PVF/g liver (1.2±0.2 ml/min/g vs.6.0±0.6 ml/min/g, p less than 0.0001) and decreased HAF (70.8±5.0 ml/min vs.41.8±5.7 ml/min, p=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4±0.8 mm Hg, p=0.046and PCS=8.3±1.2 mm Hg, p=0.025) and PVF (control=869.0±36.1 ml/min vs. terlipressin=565.6±25.7 ml/min, p less than0.0001 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±6.3ml/min, p=0.026). The results of this study suggest that terlipressin and PCS may have a role in the prevention and treatment of post-resection liver failure.

Citation

Hammond, J. S., Godtliebsen, F., Steigen, S., Guha, I. N., Wyatt, J., Revhaug, A., Lobo, D. N., & Mortensen, K. E. (2019). The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig. Clinical Science, 133(1), 153-166. https://doi.org/10.1042/CS20180858

• Journal Article Type: Article
• Acceptance Date: Dec 29, 2018
• Online Publication Date: Jan 15, 2019
• Publication Date: Jan 15, 2019
• Deposit Date: Jan 3, 2019
• Publicly Available Date: Jan 16, 2020
• Journal: Clinical Science
• Print ISSN: 0143-5221
• Electronic ISSN: 1470-8736
• Publisher: Portland Press
• Peer Reviewed: Peer Reviewed
• Volume: 133
• Issue: 1
• Pages: 153-166
• DOI: https://doi.org/10.1042/CS20180858
• Keywords: post-resection liver failure; terlipressin; portacaval shunt.
• Public URL: https://nottingham-repository.worktribe.com/output/1441025
• Contract Date: Jan 3, 2019