Temporal Lactate Kinetics and Tissue Lactate Burden in Experimental Skeletal Muscle Ischemia–Reperfusion: Associations with Inflammation, Cellular Injury, and Oxidative Stress

Background: Skeletal muscle ischemia–reperfusion (I/R) induces metabolic, inflammatory, and oxidative disturbances that may persist after restoration of blood flow. This study evaluated circulating lactate kinetics together with tissue lactate, inflammatory, cellular injury, and oxidative markers following experimental skeletal muscle I/R. Methods: Animals subjected to skeletal muscle I/R were compared with vascular I/R, bone fracture, sham, and control groups. Circulating lactate, PO2, glucose, hematocrit, and calculated oxygen saturation were assessed immediately after ischemia, approximately 15 min after reperfusion, and approximately 2 h after reperfusion. Tissue and plasma lactate, lactate dehydrogenase (LDH), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD) were also evaluated. Results: In the skeletal muscle I/R group, circulating lactate decreased from 2.19 ± 0.67 mmol/L immediately after ischemia to 1.44 ± 0.84 mmol/L during early reperfusion, before rising to 3.33 ± 1.15 mmol/L at approximately 2 h (Friedman p < 0.001), resulting in a negative lactate clearance. This biphasic pattern contrasted with the progressive decline in lactate observed in the vascular I/R and bone fracture groups. Tissue lactate was markedly elevated (11.96 ± 1.27 mmol/L) and showed positive correlations with MDA (ρ = 0.802), IL-6 (ρ = 0.741), and LDH (ρ = 0.671), all p < 0.001. Conclusions: Skeletal muscle I/R was characterized by a late increase in circulating lactate together with elevated tissue lactate and biochemical evidence of inflammatory activation, cellular injury, and oxidative stress. Serial lactate assessment may provide complementary information on post-ischemic metabolic recovery, although further validation is required.