The lactate conundrum in wound healing: Clinical and experimental findings indicate the requirement for a rapid point-of-care diagnostic

Abstract

The increasing prevalence of chronic wounds has significant financial implications for nations with advanced healthcare provision. Although the diseases that predispose to hard-to-heal wounds are recognized, their etiology is less well understood, partly because practitioners in wound management lack specialized diagnostic support. Prognostic indicators for healing may be inherent to wound biochemistry but remain invisible under routine clinical investigation; lactate is an example of this. In this study, lactate concentration in exudate obtained from 20 patients undergoing wound management in hospital was variable but in some cases approached or exceeded 20 mM. In vitro viability studies indicated that fibroblasts and endothelial cells tolerated low levels of lactate (1-10 mM), but cell viability was severely compromised by high lactate concentrations (=20 mM). Scratched monolayer experiments revealed that cell migration was affected earlier than viability in response to increasing lactate dose, and this was shown by immunocytochemistry to be associated with cytoskeletal disruption. A prototype enzyme-based colorimetric assay for lactate generating a color change that was rapid in the context of clinical practise, and capable of functioning within a gel vehicle, was developed with point-of-care dipstick applications in mind. A randomized single-blinded trial involving 30 volunteers and using a color chart to calibrate the assay demonstrated that lactate concentration could be reliably estimated with 5 mM precision; this suggesting that "physiological" and "pathological" lactate concentration could be distinguished. The present data suggest that a dipstick-type colorimetric assay could comprise a viable diagnostic tool for identifying patients at-risk from high-wound lactate.