gms | German Medical Science

Objectives: The gadolinium-based contrast agent DOTA-Gd is in daily clinical use in combination with local anesthetics for direct magnetic resonance arthrography (dMRA). However, it remains unclear whether gadolinium uptake into cartilage is influenced by co-administration of the local anesthetics bupivacaine or ropivacaine and whether DOTA-Gd alters their chondrotoxicity. The primary aim of this in vitro study was to perform gadolinium quantification in the chondrogenic matrix of 3D chondrocyte spheroids. In addition, cytotoxicity assessment of DOTA-Gd after combined exposure with local anesthetics was performed on chondrocytes grown in a 2D layer in cell culture.

Methods: Inductively coupled plasma mass spectrometry was performed to quantify gadolinium in chondrogenic spheroids following exposure to DOTA-Gd and local anesthetics. Synchrotron X-ray-fluorescence scanning was performed to analyze the spatial distribution of gadolinium in chondrogenic matrix. Metabolic activity and proliferation potential of human primary chondrocytes were analyzed after exposure to clinically relevant doses of local anesthetics and DOTA-Gd.

Results and conclusion: Gadolinium uptake is significantly enhanced following co-exposure to bupivacaine or ropivacaine. Analyzes of the spatial gadolinium distribution indicates exposure of chondrocytes to gadolinium within the chondrogenic matrix of 3D cell pellets. DOTA-Gd does not induce cytotoxic effects in chondrocytes grown in 2D at the tested doses. In addition, DOTA-Gd does not alter the chondrotoxic potential of bupivacaine and ropivacaine. Reduced cell viability induced by ropivacaine was found to be reversible while exposure to bupivacaine at clinically relevant dose leads to irreversible cell death.

Our in vitro data suggest that ropivacaine is more tolerable than bupivacaine when considering cytotoxicity in chondrocytes. Co-exposure with DOTA-Gd does not lead to additional cytotoxicity, indicating that the co-administration with local anesthetics can be considered as safe as their single use. Enhanced gadolinium uptake into chondrogenic matrix due to co-administration of local anesthetics should find attention regarding a potential influence of clinical dMRA diagnostics.