Tranexamic acid toxicity in human periarticular tissues.

OBJECTIVES: Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. METHODS: Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. RESULTS: There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. CONCLUSION: The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11-18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1.

An investigation of the pathophysiology of ischaemic neuropathy.

This study assesses the changes in the microvasculature of peripheral nerves in acute large vessel ischaemic neuropathy. An animal model of large vessel ligation, producing an ischaemic neuropathy was used: the presence and extent of the neuropathy was documented by clinical examination and nerve conduction studies. The nerve microcirculation, the "vasa nervorum" was examined using casting materials, methyl methacrylate and silicone rubber, which were in turn examined by light microscopy and scanning electron microscopy. In all, ten animals were used, all of whom showed clinical evidence of an ischaemic neuropathy 1 week post-ligation. This ischaemic neuropathy was confirmed by nerve conduction studies. Corrosion casts were produced in five of the ten animals. Examination of these casts showed that all five had an area of underfilling of the microcirculation in the region of the proximal tibial nerve with good filling of vessels proximal and distal to this, indicating that in generalised hypoperfusion states such as large vessel ligation, the area of poorest perfusion (and thus maximal damage) is not the distal vascular field, but a probable "watershed zone" between two adjacent nutrient vessels to the nerve.

Surgical anatomy of the human spleen.

Post-splenectomy sequelae are now well recognized, and conservative splenic surgery is widely advocated. However, controversies exist regarding splenic surgical anatomy. We studied 127 human spleens using anatomical dissection and a sequential injection method involving both radiology and corrosion casting, with the primary aim of examining segmental splenic anatomy and blood supply. The existence of well-defined splenic segments was confirmed and these ranged in number from 3 to 7 with a mean of 4.3. Each segment had its own arterial supply and venous drainage. The segments were separated from each other by avascular planes. Subsegments with independent blood supply were also identified. The splenic artery was found to divide into two branches; in all cases these further divided into segmental arteries supplying the central segments of the spleen. The polar segments were supplied by segmental vessels of highly variable origin and size. This study aims to highlight the importance of identifying these segmental vessels at operation when splenic conservation is considered.