Tourniquet Use During Knee Replacement Surgery May Contribute to Muscle Atrophy in Older Adults

Abstract

Muscle atrophy after total knee arthroplasty (TKA) occurs at a rate of 1% per day for the first 2 wk. Our hypothesis is that tourniquet-induced ischemia-reperfusion injury occurring during TKA influences metabolism and may contribute to atrophy. Identifying pathways that are upregulated during this critical "14-d window" after surgery may help us delineate therapeutic approaches to avoid muscle loss.

Trial registration: ClinicalTrials.gov NCT02145949.

Figure 1. Muscle Atrophy

Percent change from baseline in muscle volume at 2 and 6 weeks post-TKA. Data derived from (11). Approximately 80% of muscle atrophy measured at 6 weeks post-TKA occurred within the first 14 days after surgery. This is equivalent to a rate of atrophy of 1% per day.

Figure 2. MRI of Edema of the Mid-thigh Region

Images from mid-thigh region using MRI obtained before (A and C) and 2 weeks after TKA (B and D). Top image (A and B) shows results for a 66-year-old male patient. Bottom images (C and D) are from a 62-year-old female patient. Note the edema in the muscle tissue and surrounding subcutaneous fat region in images B and D, obtained 2 weeks after TKA.

Figure 3. Theoretical Model

We hypothesize that IR-injury contributes to muscle atrophy following TKA.

Figure 4. Signaling Pathways Altered by IR-injury during TKA

Data indicating altered cell metabolism during TKA derived from (2, 18, 41). Proteins in bold represent change in phosphorylation, protein, or transcript levels. Up arrows represent increased phosphorylation. Down arrows represent decreased phosphorylation. Net effect on processes is shown. Myosin and eIF3f are examples of proteins targeted for degradation. Hashed lines indicate translocation or indirect pathways. $ Represents the fact that BNIP3 levels in the nucleus decreased significantly during TKA, but a reciprocal increase in the cytoplasmic fraction was not measured. * Represents change in both protein and transcript levels; # Represents change in transcript levels; § Represents increase in total protein; † Represents cleaved caspase; ‡ Represents trend, p < 0.1.

Figure 5. Muscle Cell Swelling

Rightward shift in cross-sectional area frequency distribution of Type I, Type IIa, and Type IIx fibers. The shift represents cell swelling. Fibers from left (baseline, white boxes) to right (2.3 hours post-TKA, black boxes; range 84–181 minutes). The average tourniquet time was 39 ± 4 min (mean ± SD); range 33–44 minutes. Change from baseline to post-TKA CSA is significant for each fiber type (p < 0.05). Data from Muyskens et al, (33).

Figure 6. Gene Network Up Regulated after TKA

The image represents a subset of the entire network from Muyskens et al. (33). PIM-1 highly up regulated is a central node. Green nodes are genes from our dataset; the grey nodes are key signaling pathways discussed. The size of the green nodes relates to the degree of up regulation. The diagram was made using Cytoscape.