Dose-response effects of pentoxifylline on erythrocyte filterability: Clinical and animal model studies

Ambrus, Julian L.; Anain, Joseph M.; Anain, Shirley M; Anain, Paul; Stadler, S; Brobst, Joyce A; Cobert, Barton; Savitsky, J. Philip

doi:10.1038/clpt.1990.117

Cited by 30 publications

(15 citation statements)

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“…In addition, pentoxifylline increases phosphorylation of erythrocyte membrane proteins by "facilitating magnesium-dependent protein kinase and inhibiting calcium dependent phosphoprotein phosphatase." 16 The end result of this series of interactions is an increase in membrane phosphoproteins, believed to be responsible for the improvement of erythrocyte flexibility. Also, two other effects of pentoxifylline relate to its hemorrheologic properties: 1) its reduction in platelet aggregation presumed to be mediated by an effect on prostacyclin synthesis and release; and 2) its reduction in plasma fibrinogen levels.…”

Section: Discussionmentioning

confidence: 99%

The Use of Pentoxifylline in Microvascular Surgery

Kronen

Ferder²,

Hunzicker³

et al. 1994

J reconstr Microsurg

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The authors studied the effect of pentoxifylline (Trental), a hemorrheologic agent that increases erythrocyte flexibility and augments microcirculatory blood flow, on the patency of a known thrombosis model. In Sprague-Dawley rats, a double-blind study was performed, with animals receiving either intraperitoneal injections of pentoxifylline (20 mg/kg/day) or saline in an equivalent volume, 4 weeks prior to surgery and continued for 1 week postoperatively. In all animals, the left femoral artery was used for a 2-mm arterial inversion graft (AIG), and the contralateral femoral artery for a 2-mm crush injury model. In the control group, patency of the AIG was 0 percent (0/19) and that of the crush model 31 percent (6/19). The pentoxifylline-treated group showed an AIG patency of 37 percent (7/19) and a crush model patency of 84 percent (16/19). p values were .004 and .005, respectively. Furthermore, hematoma formation was associated with none of the control sides (0/38) and only with 5 percent (2/38) of the pentoxifylline-treated animals. This study demonstrated statistically significant improvement on microvascular patency in animals treated with pentoxifylline, whether they were in the crush or the arterial inversion graft groups. The clinical ramifications of using a hemorrheologic agent that improves microvascular circulation, without effecting changes in coagulation, are apparent.

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Section: Discussionmentioning

confidence: 99%

The Use of Pentoxifylline in Microvascular Surgery

Kronen

Ferder²,

Hunzicker³

et al. 1994

J reconstr Microsurg

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“…This antiproteinuric effect has been related to an increase in erythrocyte deformability with reduction of blood viscosity and a subsequent decrease of glomerular hydraulic pressure (51), to a blockade of adenosine receptors (52), and based on its anti-TNF-␣ properties (53,54), the modulation of immune and inflammatory responses has also been suggested as a potential antiproteinuric mechanism of PTF (7,8,19). In our study, in addition to a decrease of UAE, a significant reduction of serum and urinary TNF-␣ levels was observed in patients who received PTF (14.9 and 13%, respectively).…”

Section: Discussionmentioning

confidence: 99%

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Navarro¹,

Mora²,

Muros³

et al. 2005

Journal of the American Society of Nephrology

115

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Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for >1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (n ‫؍‬ 30) or to a control group (n ‫؍‬ 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-␣ (R ‫؍‬ 0.53, P < 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; P < 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was ؊16.7 and 5.5%, respectively (between-group comparison, P < 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-␣ also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (P < 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-␣ in patients who were treated with PTF (R ‫؍‬ 0.49, P < 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-␣ excretion.

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“…The clinical benefit of the drug is attributed to improved microvascular blood flow. Proposed effects on blood flow include increased RBC and leukocyte deformability, decreased neutrophil function, decreased RBC aggregation and promotion of thrombolysis (Franzini et al, 1988;Ambrus et al, 1990). Studies in horses indicate that pentoxifylline administration results in improvement in RBC deformability but has no effect on neutrophil deformability or function (Geor et al, 1992;Weiss et al, 1992a).…”

Section: Introductionmentioning

confidence: 96%

The effects of furosemide and pentoxifylline on the flow properties of equine erythrocytes:In vitro studies

1994

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The effects of various concentrations of furosemide and pentoxifylline on equine RBC in vitro were evaluated to facilitate better understanding of the potential effects of these drugs on blood flow properties. Furosemide induced increased mean cell volume (MCV), increased RBC potassium concentration, increased whole blood viscosity, and decreased the RBC filtrability. These data indicate that furosemide may block the RBC membrane transport pathways resulting in potassium and water retention. The increase in size and the resultant decrease in the surface-area-to-volume ratio may have caused the impaired RBC filtrability and increased blood viscosity. Pentoxifylline improved RBC filtrability without changing the RBC size or the potassium or chloride concentrations, suggesting that pentoxifylline may increase the deformability of the RBC membrane. The study indicated that pentoxifylline has potential therapeutic applications for improving microvascular blood flow but that furosemide may have adverse effects on blood flow.

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Dose-response effects of pentoxifylline on erythrocyte filterability: Clinical and animal model studies

Cited by 30 publications

References 0 publications

The Use of Pentoxifylline in Microvascular Surgery

The Use of Pentoxifylline in Microvascular Surgery

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

The effects of furosemide and pentoxifylline on the flow properties of equine erythrocytes:In vitro studies

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