Pentoxifylline Improves Pulmonary Gas Exchange: DISCUSSION

3 May

The action of pentoxifylline on the rheologic prop­erties of blood and its use in the treatment of periph­eral vascular disease have been reviewed by Muller. Pentoxifylline appears to improve peripheral circula­tion, and thereby peripheral gas exchange, by several mechanisms that reduce blood viscosity. This in­cludes (1) increasing red blood cell deformability, (2) inhibiting platelet aggregation, and (3) promoting fibrinolysis. In addition, this medication has been shown to increase the cardiac index and decrease vascular resistance. Our data indicate that pentoxi­fylline improves indices of gas exchange in patients with COPD and in healthy volunteers during exercise.

Funding limitations precluded use of a placebo- controlled double-blinded crossover trial on a larger group of patients. Although it might have made our statistics more rigorous, the consistency of our data suggests that it would not have altered our observa­tions. Further study, however, is needed to confirm our observations.

Clinically observable changes in both treadmill walk time and Deo could not be appreciated until the third to sixth week of treatment. This delay in effect is consistent with reports suggesting a two- to four-week latent period. Backward extrapolation of the data, however, indicates that changes in both Deo and treadmill walk time probably began earlier in the course of treatment (Fig 2 and 3). In line with this, we recently received a report of an increase of 7 mm Hg in Pa02 (from 54 to 61 mm Hg) in a patient with severe COPD after one week of therapy (Jose Luis Reggiani, personal communication). The observed delay, there­fore, may mean that maximal effect, which is due both to a rapid onset phase—that includes the cardiovas­cular effects and increased erythrocyte flexibil­ity, which can occur after adequate blood levels of pentoxifylline are reached—and to a slower, more sustained effect involving reduction in fibrinogen levels—takes one to two weeks. Similarly, the contin­uing effect that we observed after therapy had been terminated may reflect the time required for fibrino­gen levels to increase to pretreatment levels.
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Another possible explanation for the delay between onset and maximum effect is that pentoxifylline alters the flexibility of new erythrocytes. Fedorov and Ermilchenko reported that pentoxifylline in vitro causes methylation of nuclear homogenates in rat bone marrow. Although there is no increase in erythropoi­etin formation, the possibility exists that newly formed erythrocytes may have improved flexibility that is therapeutically more important than the influ­ence of the drug on mature circulating erythrocytes.

Although we cannot rule out the possibility that the increased walk time observed in the COPD treatment group was due to the same improvement in peripheral circulation observed in patients with intermittent claudication, this would not account for the ob­served improvement seen at rest.

We also cannot completely rule out that the in­creased walk time reflected a placebo effect or that the improvement was caused by bronchodilation. The concurrent increases in Deo, Soxi02, and the pub­lished changes in cardiovascular function, all of which are consistent with increased walk time, argue against a placebo effect. Kamagra Oral Jelly

Although pentoxifylline is a methyl xanthine, we did not observe any increase in expiratory airflow that would suggest bronchodilation. This is consistent with the absence of reports in the literature suggesting that pentoxifylline has a significant bronchodilator effect.