Pentoxifylline attenuates the local and systemic inflammatory response after infrarenal abdominal aortic ischemia-reperfusion

Article type: Research Article

Authors: Nagy, Tibor^{a; *} | Hardi, Péter^a | Takács, Ildikó^a | Tóth, Mónika^a | Petrovics, Laura^a | Jancsó, Gábor^a | Sínay, László^b | Fazekas, Gábor^b | Pintér, Örs^c | Arató, Endre^b

Affiliations: [a] Department of Surgical Research and Techniques, Medical School, University of Pécs, Hungary | [b] Department of Vascular Surgery, Medical School, University of Pécs, Hungary | [c] Heart Institute, Medical School, University of Pécs, Hungary

Correspondence: [*] Corresponding author: Tibor Nagy, M.D., PhD, Department of Surgical Research and Techniques, Medical School, University of Pécs, 7624 Pécs, Szigeti út 12, Hungary. Tel.: +36 72 536 330; E-mail: [email protected].

Abstract: AIMS: We studied the new anti-inflammatory effects of non-specific phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) on ischaemia-reperfusion injury and postconditioning of the lower extremities. We aimed to examine the oxidative stress parameters (OSP), the inflammatory response and the changes in structure of skeletal muscle after revascularization surgery. METHODS: 50 Wistar rats in five groups underwent a 60 min infrarenal aortic cross clamping. After the ischaemia in IR+PC group ischemic postconditioning was performed, intermittent 15 seconds reperfusion, 15 seconds ischaemic periods were applied four times. The ischemic phase was followed by a 120 min of reperfusion. In IR+PTX group the animals were treated with PTX. In IR+PC+PTX group both ischemic postconditioning and PTX treatment were performed. Blood samples and biopsy from quadriceps muscle were collected. Plasma malondialdehyde, reduced glutathione, -SH-groups, TNF-alpha, IL-6 concentrations and superoxide dismutase enzyme activity were measured. RESULTS: The levels of OSP and the inflammatory proteins were significantly higher in the IR group. PTX treatment and PC could significantly decrease the levels of OSP and inflammatory proteins. When the animals were co-treated with PTX and PC the results were even better. CONCLUSIONS: Inhibition of PDE by PTX could markedly decrease the inflammatory response and moderate the ischaemia-reperfusion damages after lower limb ischemia and reperfusion. Administration of PTX could potentiate the beneficial effects of PC.

Keywords: Postconditioning, reperfusion injury, vascular surgery, reactive oxygen species, TNF-alpha, leukocyte, inflammatory response, pentoxifylline (PTX)

DOI: 10.3233/CH-16169

Journal: Clinical Hemorheology and Microcirculation, vol. 65, no. 3, pp. 229-240, 2017