Skeletal muscle ischemia-reperfusion injury and cyclosporine A in the aging rat

Old patients exhibit muscle impairments and increased perioperative risk during vascular surgery procedures. Although aging generally impairs protective mechanisms, data are lacking concerning skeletal muscle in elderly. We tested whether cyclosporine A (CsA), which protects skeletal muscle from ischemia-reperfusion (IR) in young rats, might reduce skeletal muscle mitochondrial dysfunction and oxidative stress in aging rats submitted to hindlimb IR. Wistar rats aged 71-73 weeks were randomized to IR (3 h unilateral tourniquet application and 2 h reperfusion) or IR + CsA (10 mg/kg cyclosporine IV before reperfusion). Maximal oxidative capacity (V_Max), acceptor control ratio (ACR), and relative contribution of the mitochondrial respiratory chain complexes II, III, IV (V_Succ), and IV (V_TMPD/Asc), together with calcium retention capacity (CRC) a marker of apoptosis, and tissue reactive oxygen species (ROS) production were determined in gastrocnemius muscles from both hindlimbs. Compared to the nonischemic hindlimb, IR significantly reduced mitochondrial coupling, V_Max (from 7.34 ± 1.50 to 2.87 ± 1.22 μMO₂/min/g; P < 0.05; -70%), and V_Succ (from 6.14 ± 1.07 to 3.82 ± 0.83 μMO₂/min/g; P < 0.05; -42%) but not V_TMPD/_Asc. IR also decreased the CRC from 15.58 ± 3.85 to 6.19 ± 0.86 μMCa²⁺/min/g; P < 0.05; -42%). These alterations were not corrected by CsA (-77%, -49%, and -32% after IR for V_Max, V_Succ, and CRC, respectively). Further, CsA significantly increased ROS production in both hindlimbs (P < 0.05; +73%). In old rats, hindlimb IR impairs skeletal muscle mitochondrial function and increases oxidative stress. Cyclosporine A did not show protective effects.