Pentoxifylline Treatment in Patients with Occlusive Peripheral Arterial Disease. Circulatory Changes and Effects on Prostaglandin Synthesis

Abstract

Pentoxifylline has recently been reported to stimulate in vitro the synthesis of prostacyclin. However it is not known so far whether the drug is able to stimulate prostacyclin synthesis in man also in vivo. In the present study the effects of pentoxifylline on prostaglandin synthesis and several circulatory parameters were studied in 10 controls and 10 patients with occlusive arterial disease after acute i.v. and medium term oral treatment. Prostacyclin (as 6-keto-PGF1 alpha) and PGE2 plasma concentrations have been measured together with arterial blood flow, peripheral vascular resistance, platelet aggregation and red blood cell deformability. Pentoxifylline was found both in healthy subjects and patients to significantly increase prostacyclin plasma concentration after i.v. treatment. In medium term oral treatment prostacyclin concentration was found to increase only two hours after administration and not 8 hours after. No significant variations in PGE2 plasma concentration were found at any time in both groups. Pentoxifylline significantly enhanced resting and post-ischemic blood flow of the lower limbs and simultaneously decreased peripheral vascular resistance both in healthy subjects and patients. Different grades of delayed platelet aggregation and increased red blood cell deformability were also observed. In conclusion results of the present placebo controlled study show that pentoxifylline increases arterial blood flow in patients with occlusive arterial disease. Moreover pentoxifylline induces a temporary stimulation of prostacyclin synthesis which can be suggested to contribute to the clinical activity of the drug as far as an antithrombotic effect in terms of inhibition of platelet aggregation is concerned.

Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury

“…PTX was recently reported to stimulate in vitro synthesis of prostacyclin in various cell systems and induce a temporary stimulation of PGE 2 in occlusive peripheral disease [9,24]. Reed and DeGowin [25] thought that the inhibitory effects of PTX on natural killer cell activity are parallel to the stimulation of PGE 2 synthesis in the patients with peripheral vascular disease.…”

Pentoxifylline in Ischemia-Induced Acute Kidney Injury in Rats

“…[2,3] Pentoxifylline, a methylxanthine derivative (1-(5-oxohexyl)-3,7-dimethylxanthine) used to treat patients with peripheral arterial disease, is a nonspecific phosphodiesterase (EC 3.1.4.17) inhibitor that causes increased levels of cyclic-AMP (3′,5′-AMP), leading to vasodilatation, improved erythrocyte flexibility, and inhibition of platelet aggregation, lowering blood viscosity and increasing tissue oxygenation. [5][6][7] Pentoxifylline also down-regulates the production of interleukin-1, TNF-a, and interferon-g. [8][9][10][11] It has been shown to improve endothelial function in a model of endotoxemia-related AKI. [12] In addition, it inhibits the proliferation of fibroblasts and mesangial cells, and reduces the production of extracellular matrix.…”

Protective Effects of Pentoxifylline Treatment on Gentamicin-Induced Nephrotoxicity in Rats

“…[24][25][26] Pentoxifylline has other functions as well, including the inhibition of platelet adherence [27] and endothelium-dependent vascular relaxation. [28,29] Recently, PTX has gained considerable interest as a ROS scavenger. Several in vitro studies have confirmed the potential antioxidant effects of this drug.…”