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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 (
=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,
<0.0001) and PVF/g liver (1.2 ± 0.2 compared with 6.0 ± 0.6 ml/min/g,
<0.0001) and decreased HAF (70.8 ± 5.0 compared with 41.8 ± 5.7 ml/min,
=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4 ± 0.8 mmHg,
=0.046 and PCS = 8.3 ± 1.2 mmHg,
=0.025) and PVF (control = 869.0 ± 36.1 ml/min compared with terlipressin = 565.6 ± 25.7 ml/min,
<0.0001 and PCS = 488.4 ± 106.4 ml/min,
=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,
=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.