SLR - November 2014 - Katie Hoang

Inhibition of Chondrocyte and Synovial Cell Death After Exposure to Commonly Used Anesthetics: Chondrocyte Apoptosis After Anesthetics

Reference: Allison J. Rao, Tyler R. Johnston, Alex H.S. Harris, R. Lane Smith, John G. Costouros. Inhibition of Chondrocyte and Synovial Cell Death After Exposure to Commonly Used Anesthetics: Chondrocyte Apoptosis After Anesthetics. Am J Sports Med. 2014; 42(1):50-58

Scientific Literature Review

Reviewed By: Katie Hoang, DPM
Residency Program: North Colorado Podiatric Medicine and Surgery Residency, Greeley, CO

Podiatric Relevance: In foot and ankle surgery, intra-articular diagnostic blocks are commonly performed. Intra-articular injections are given with steroid to help arthritic joints. During ankle scopes many surgeons insufflate the ankle joint utilizing lidocaine with epinephrine. Caspase inhibitor could be a viable option to reverse the negative effects of local anesthetic on chondrocytes and synovial cells.

Methods: Six wells of 100,000 human chondrocytes were subdivided into four treatment groups (normal saline, 0.5 percent bupivacaine, 0.5 percent ropivacaine, 1 percent lidocaine). A LIVE/DEAD viability/cytotoxicity kit was then used to assess short-term exposure after 30, 45, 60, 75, 90, 105, and 120 minutes of exposure. The same treatment groups in addition to 1:1000 epinephrine were then added to chondrocyte and synovial cell cultures for 90 minutes. Apoptosis was analyzed at one, three, five, and seven days after exposure utilizing caspase-3 antibody staining and TUNEL assay. Apoptosis was inhibited by z-vad-fmk.

Results: LIVE/DEAD assay bupivacaine exposure resulted in 18.25 percent increase in cell death vs. normal saline and 14.8 increase vs. ropivacaine. Effects of bupivacaine increased with exposure time.

Chondrocyte apoptosis TUNEL assay, across all time points, bupivacaine and epinephrine exposure resulted in the highest percentage apoptosis with 62.9 and 62 respectively. Ropivacaine had the highest rescue effect of chondrocyte apoptosis with caspase inhibitor with 45.9 percent without and 0.96 percent with. TUNEL assay of synovial cell apoptosis was greater than 80 percent with all anesthetics across all time points. Ropivacaine had the highest rescue effect with caspase inhibitor with an 84 percent decrease in apoptosis of synovial cells.

Chondrocyte apoptosis antiactivated caspase-3-staining bupivacaine and lidocaine had the highest percentage across all time points, 20 percent and 15.7 percent respectively. Bupivacaine had the highest response to caspase inhibitor with 3.8 percent. Synovial cell apoptosis had greater than 30 percent apoptosis in bupivacaine, lidocaine, and ropivacaine groups assessed with antiactivated caspase-3-staining. Caspase inhibitor had the greatest effect with lidocaine with a 32 percent reduction in synovial cell apoptosis.

Conclusions: This study reports the presence of apoptosis of synovial cells as well as confirms the presences of apoptosis of chondrocytes reported in prior studies. This study demonstrates successful reversal of apoptosis with concurrent administration with caspase inhibitor. Apoptosis and cartilage degeneration plays a role in arthritis. Further studies and clinical correlation is needed to explore the suggested benefits of concurrent administration of caspase inhibitor with use of local anesthetic.  

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