Protective Effects of Pentoxifylline on Peripheral Microcirculatory Dysfunction and Renal Cortical Oxygen Deficiency in a Rat Model of LPS-Induced Sepsis.

Abstract

OBJECTIVE: Sepsis is associated with hypotension, tissue hypoperfusion, and microcirculatory dysfunction leading to multi-organ failure and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is reported to improve blood flow and viscosity. The aim of this study was to investigate the efficacy of PTX on peripheral and renal microcirculatory alterations in sepsis. METHODS: Fully instrumented Wistar albino rats were randomized as the control group (only surgery), only lipopolysaccharide (LPS) group without treatment (T1), LPS group with PTX treatment (LPS&#x2009;+&#x2009;PTX), LPS group treated with only fluid resuscitation (Ringer's acetate; RA), LPS&#x2009;+&#x2009;RA, LPS group with combined treatment with PTX and RA (LPS&#x2009;+&#x2009;PTX&#x2009;+&#x2009;RA) for 3&#x2009;h (T2, T3 and T4). The systemic hemodynamics, renal oxygenation, leg muscle microcirculation, histological damage, and inflammatory and endothelial injury markers were analyzed. RESULTS: The renal cortical microvascular oxygen pressure (c&#x3bc;PO) was improved by the PTX, RA, and PTX&#x2009;+&#x2009;RA treatments compared to the LPS group (p&#x2009;<&#x2009;0.05). The proportions of perfused vessels (PPV) and red blood cell velocity (RBCv) were significantly restored by PTX and RA compared with the LPS group at T4 (p&#x2009;<&#x2009;0.05). Renal damage and inflammatory cell infiltration were reduced by PTX and RA together compared with RA alone (p&#x2009;<&#x2009;0.05). CONCLUSION: In this study, we found that PTX may protect renal oxygenation, peripheral (muscle) microcirculation, renal damage, and tissue inflammatory cell infiltration in a rat model of LPS-induced sepsis.