Muscles Susceptibility to Ischemia-Reperfusion Injuries Depends on Fiber Type Specific Antioxidant Level

Muscle injury resulting from ischemia-reperfusion largely aggravates patient prognosis but whether and how muscle phenotype modulates ischemia-reperfusion-induced mitochondrial dysfunction remains to be investigated. We challenged the hypothesis that glycolytic muscles are more prone to ischemia-reperfusion-induced injury than oxidative skeletal muscles. We therefore determined simultaneously the effect of 3 h of ischemia induced by aortic clamping followed by 2 h of reperfusion (IR,; n; = 11) on both; gastrocnemius; and; soleus; muscles, as compared to control animals (C,; n; = 11). Further, we investigated whether tempol, an antioxidant mimicking superoxide dismutase, might compensate a reduced defense system, likely characterizing glycolytic muscles (IR-Tempol,; n; = 7). In the glycolytic; gastrocnemius; muscle, as compared to control, ischemia-reperfusion significantly decreased mitochondrial respiration (-30.28 ± 6.16%,; p; = 0.003), increased reactive oxygen species production (+79.15 ± 28.72%,; p; = 0.04), and decreased reduced glutathione (-28.19 ± 6.80%,; p; = 0.011). Less deleterious effects were observed in the oxidative; soleus; muscle (-6.44 ± 6.30%, +4.32 ± 16.84%, and -8.07 ± 10.84%, respectively), characterized by enhanced antioxidant defenses (0.63 ± 0.05 in; gastrocnemius vs; . 1.24 ± 0.08 μmol L; -1; g; -1; in; soleus; ). Further, when previously treated with tempol, glycolytic muscle was largely protected against the deleterious effects of ischemia-reperfusion. Thus, oxidative skeletal muscles are more protected than glycolytic ones against ischemia-reperfusion, thanks to their antioxidant pool. Such pivotal data support that susceptibility to ischemia-reperfusion-induced injury differs between organs, depending on their metabolic phenotypes. This suggests a need to adapt therapeutic strategies to the specific antioxidant power of the target organ to be protected.