Pentoxifylline reverses oxidative mitochondrial defect in claudicating skeletal muscle.
OBJECTIVE
Previous morphologic studies and phosphorus nuclear magnetic resonance spectroscopy (31P MRS) have suggested a primary mitochondrial defect in claudicating skeletal muscle. We hypothesized that pentoxifylline may alleviate this defect.


METHODS
The response of calf muscle bioenergetics to pentoxifylline was evaluated in 10 male, nondiabetic claudicants with 31P MRS and standard treadmill testing before and after 12 weeks of pentoxifylline therapy. Phosphocreatine (PCr) and adenosinodiphosphate (ADP) recovery rate constants, two very sensitive measures of oxidative mitochondrial function, were measured.


RESULTS
Seven of the 10 subjects had abnormal baseline PCr (<0.015 s(-1)) and ADP (<0.024 s(-1)) recovery rate constants. These 7 had significant improvement in mitochondrial function with pentoxifylline; their PCr recovery rate constants increased from 0.009 +/- 0.002 to 0.013 +/- 0.002 s(-1) (P = 0.013) and their ADP recovery rate constants increased from 0.015 +/- 0.002 to 0.022 +/- 0.002 s(-1) (P = 0.004). The remaining 3 patients had normal baseline constants and demonstrated no improvement after pentoxifylline therapy. Baseline PCr and ADP recovery rate constants inversely correlated with their corresponding percentage of improvement after pentoxifylline (P < 0.05). In addition the percentage of improvement in the PCr and ADP recovery rate constants correlated with the percentage of improvement in initial claudication distance and maximum walking capacity (P < 0.05).


CONCLUSIONS
Pentoxifylline improves the mitochondriopathy of claudicating muscle, producing the most improvement in limbs with the worse baseline mitochondrial function. These results point to a potential new mode of action for pentoxifylline in the treatment of claudication and identify a subgroup of patients with the best potential for improvement with treatment.
Pipinos
Iraklis I
II
Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska 68198-3280, USA.
Boska
Michael D
MD
Shepard
Alexander D
AD
Anagnostopoulos
Petros V
PV
Katsamouris
Asterios
A
D000368:Aged; D005080:Exercise Test; D006801:Humans; D007383:Intermittent Claudication / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010431:Pentoxifylline / Q000008:administration & dosage*; D010759:Phosphorus Isotopes; D011877:Radionuclide Imaging; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010759:Phosphorus Isotopes; D014665:Vasodilator Agents; D010431:Pentoxifylline