Intraportal versus Systemic Pentoxifylline Infusion after Normothermic Liver Ischemia: Effects on Regional Blood Flow Redistribution and Hepatic Ischemia-Reperfusion Injury

Abstract

Pentoxifylline (PTX) has been shown to have beneficial effects on microcirculatory blood flow. In this study we evaluate the potential hemodynamic and metabolic benefits of PTX during hepatic ischemia. We also test the hypothesis that portal PTX infusion can minimize the I/R injury when compared to systemic infusion. Methods. Twenty-four dogs (18.1 ± 0.7 kg) were subjected to portal triad occlusion (PTO) for 45 min. The animals were assigned to 3 groups: CT (control, PTO, n = 8), PTX-syst (PTO + 25 mg/Kg of PTX IV, n = 8), and PTX-pv (PTO + 25 mg/Kg of PTX in the portal vein, n = 8). Animals were followed for 120 min. Systemic hemodynamics, gastrointestinal tract perfusion, oxygen-derived variables, and liver enzymes were evaluated throughout the experiment. Results. Animals treated with PTX presented significantly higher CO in the first hour after reperfusion, when compared to the CT (~3.7 vs. 2.1 L/min, P < 0.05). Alanine aminotransferase (ALT) was similar in the PTX groups two hours after reperfusion but significantly higher in the CT (227 vs. ~64 U/L, P < 0.05). Conclusion. PTX infusion was associated with hemodynamic benefits and was able to minimize liver injury during normothermic hepatic I/R. However, local PTX infusion was not associated with any significant advantage over systemic route.

Figure 1

(a) Cardiac output (L/min), (b) and (c) portal vein and hepatic artery blood flows (mL/min) during the experimental protocol. The animals were randomly assigned into three groups: CT (control, portal triad clamping, n = 8), PTX-syst (portal triad clamping + 25 mg/Kg of PTX intravenous systemically, n = 8), and PTX-pv (portal triad clamping + 25 mg/Kg of PTX in the portal vein, n = 8). BL: baseline; P45: 45 min after Pringle's maneuver; R15, R60, and R120: 15, 60, and 120 min after reperfusion. Data are shown as mean ± SEM. ^aIndicates P < 0.05 for PTX-pv and PTX-sys versus BL; ^bbindicates P < 0.05 for PTX-pv and PTX-sys versus CT; ^cindicates P < 0.05 for PTX-sys versus BL; ^dindicates P < 0.05 for PTX-sys versus CT.

Figure 2

(a) Alanine transaminase (ALT, U/L) and (b) lactate dehydrogenase (LDH, U/L) during the experimental protocol. BL: baseline; P45: 45 min after Pringle's maneuver; R15, R60, and R120: 15, 60, and 120 min after reperfusion. Groups are the same as in Figure 1. Data are shown as mean ± SEM.  ^bIndicates P < 0.05 for CT versus PTX-pv and PTX-sys.