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Pentoxifylline reverses oxidative mitochondrial defect in claudicating skeletal muscle
Iraklis I Pipinos1, Michael D Boska, Alexander D Shepard
1Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska 68198-3280, USA.
The Journal of Surgical Research
|February 14, 2002
Summary
Pentoxifylline treatment improved mitochondrial function in patients with claudication. This drug enhanced calf muscle bioenergetics, particularly in those with more severe baseline mitochondrial defects, suggesting a new therapeutic approach.
Area of Science:
- Biomedical science
- Exercise physiology
- Pharmacology
Background:
- Skeletal muscle mitochondrial dysfunction is implicated in claudication.
- Phosphorus nuclear magnetic resonance spectroscopy (31P MRS) has indicated primary mitochondrial defects in claudicating muscle.
- Pentoxifylline is being investigated for its potential to alleviate these defects.
Purpose of the Study:
- To evaluate the effect of pentoxifylline on calf muscle bioenergetics in patients with claudication.
- To determine if pentoxifylline can improve mitochondrial function, as measured by phosphocreatine (PCr) and adenosinodiphosphate (ADP) recovery rate constants.
- To explore the correlation between baseline mitochondrial function, treatment response, and walking capacity.
Main Methods:
- A 12-week pentoxifylline therapy was administered to 10 male, nondiabetic claudicants.
- Calf muscle bioenergetics were assessed using 31P MRS and treadmill testing before and after treatment.
- Key measures included PCr and ADP recovery rate constants, indicators of oxidative mitochondrial function.
Main Results:
- Seven out of 10 subjects showed abnormal baseline PCr and ADP recovery rates.
- Pentoxifylline significantly improved mitochondrial function in these 7 subjects (P = 0.013 for PCr, P = 0.004 for ADP).
- Improvements in mitochondrial function correlated with enhanced claudication distance and walking capacity.
Conclusions:
- Pentoxifylline effectively improves mitochondriopathy in claudicating skeletal muscle.
- The greatest benefits were observed in patients with the most impaired baseline mitochondrial function.
- These findings suggest a novel mechanism for pentoxifylline in treating claudication and identify patient subgroups likely to benefit most.