TY - JOUR
T1 - Pentoxifylline reverses oxidative mitochondrial defect in claudicating skeletal muscle
AU - Pipinos, Iraklis I.
AU - Boska, Michael D.
AU - Shepard, Alexander D.
AU - Anagnostopoulos, Petros V.
AU - Katsamouris, Asterios
N1 - Funding Information:
Presented at the Annual Meeting of the Association for Academic Surgery, Philadelphia, Pennsylvania, November 18–20, 1999. 1This work was supported by funds provided by the Henry Ford Health System.
PY - 2002
Y1 - 2002
N2 - 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 adenosino-diphosphate (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.
AB - 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 adenosino-diphosphate (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.
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U2 - 10.1006/jsre.2001.6292
DO - 10.1006/jsre.2001.6292
M3 - Article
C2 - 11796008
AN - SCOPUS:0036353399
VL - 102
SP - 126
EP - 132
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 2
ER -