Endothelial cell compatibility of clindamycin, gentamicin, ceftriaxone and teicoplanin in Bier's arterial arrest

Abstract

In patients with infected diabetic foot lesions, and gangrenous, peripheral, occlusive arterial disease, it is important to achieve high concentrations of antibiotics in the tissues, as the extent of amputation is often influenced by the presence of infection. Local transvenous pressure injection of antibiotics, in Bier's arterial arrest, allows high local tissue concentrations to be attained in the extremities. Information on the endothelial compatibility of antibiotics in high concentrations combined with the effect of reperfusion injury following tissue hypoxia is lacking. To evaluate the effect of clindamycin, gentamicin, ceftriaxone and teicoplanin injected in Bier's arterial arrest, on endothelial cells, an in-vitro model using human umbilical venous endothelial cells (HUVEC) has been devised. The intracellular levels of purine nucleotides, reflecting DNA/RNA synthesis, energy production and signal transduction of these cells were measured by means of high-performance liquid chromatography. Incubation of cells with 10 mg/mL clindamycin, gentamicin, ceftriaxone and teicoplanin for 20 min resulted in no significant decline of intracellular purines. Levels of purines obtained after exposure of the cells to 0.1 mmol/L hydrogen peroxide (H2O2), to simulate reperfusion injury, were not significantly different from those obtained from cells allowed to recover after antibiotic exposure. These findings indicate that the infusion of high doses of antibiotics, during Bier's arterial arrest, is compatible with maintenance of endothelial cell function, even in the presence of increased free radical activity, provided the exposure is limited to 20 min.