Transcriptional profiling and muscle cross‐section analysis reveal signs of ischemia reperfusion injury following total knee arthroplasty with tourniquet

Total knee arthroplasty (TKA) is the most common and cost‐effective treatment for older adults with long‐standing osteoarthritis. Projections indicate that nearly 3.5 million older adults will undergo this procedure annually by the year 2030. Thus, understanding the factors that lead to optimal outcomes is of great clinical interest. In the majority of cases, tourniquet is applied during surgery to maintain a clear surgical field, however, there is debate as to whether this intervention is completely benign. In particular, muscle atrophy is a significant factor in preventing full functional recovery following surgery, and some evidence suggests that tourniquet application and the associated ischemia–reperfusion injury that results contributes to muscle atrophy. For this reason, we examined tissue level changes in muscle in TKA patients following surgery and found that there was a significant increase in cross‐sectional area of muscle fibers of all types. Furthermore, to detect changes not evident at the tissue level, we performed NextSeq analysis to assess the transcriptional landscape of quadriceps muscle cells following TKA with tourniquet and found 72 genes that were significantly upregulated. A large proportion of those genes regulate cell stress pathways, suggesting that muscle cells in our cohort of older adults were capable of mounting a significant response to cell stress. Furthermore, factors related to complement were upregulated, suggesting tourniquet may play a role in priming cells to ischemia reperfusion injury. Therefore, our analysis reveals potential harms of tourniquet during TKA, thus suggesting that surgeons should consider limiting its use. During TKA, muscle cells are subjected to prolonged oxygen deficiency that alters cell metabolism in order to reduce energy (ATP) demand and maintain cell homeostasis until blood flow is restored. Our findings reveal that within 2–3 h of surgery ischemia‐reperfusion injury occurs as revealed by swelling of all three muscle cell types swell and our NextSeq data suggest the activation of several cell stress‐related pathways including MAPK, JNK, JAK‐STAT, NFkB, Akt, and p53 may play a role.