Efficacy of media enriched with nonlactate-generating substrate for organ preservation: in vitro and clinical studies using the cornea model.

Abstract

Using a rabbit cornea model, our recent study demonstrated that Chen Medium (CM), an isotonic media enriched with nonlactate-generating high-energy substrates, is very effective for organ preservation. In the present study, the efficacy of CM is further evaluated with human corneas The effectiveness of CM and Optisol for preserving the endothelial integrity of human corneas in vitro was evaluated by scanning electron microscopy. Clinical efficacy was evaluated in a total of 83 patients: 10 patients with keratoconus grafted randomly with either CM- or Optisol-stored cornea of the same donor, and 73 patients with various conditions grafted with CM-stored corneas. After surgery, visual acuity and quality of the graft were monitored for up to 4.6 years. The scanning electron microscopic study revealed that after 11-day storage at 4 degrees C, the CM-stored cornea had only marginal disruptive changes, 9.4+/-1.1%, in endothelial cells, as opposed to 42.4+/-4.6% of the Optisol-stored cornea. All 78 CM-stored corneas, including 67 with 12.2- to 17.7-hr death-to-storage time, 3-7.6 days of storage time, and initial marginal quality before storage, were successfully transplanted. These grafts were thin and clear, with an excellent epithelial integrity and without significant changes in endothelial cell density. Five Optisol-stored corneas were also successfully grafted; one of them, however, was edematous for about 4 weeks, and all the grafts were slightly thicker with substantial endothelial cell loss. Using a cornea model, present and recent studies show that CM is very effective for preserving tissue viability and endothelial integrity. Previous study revealed that CM-stored tissues maintained high levels of ATP and metabolic function, with suppression of lactate formation and accumulation. Thus, these findings support the concept that preservation of tissue viability is closely associated with the ability of the tissues to retain metabolic activity, to generate ATP efficiently, and to prevent acidosis effectively during storage.