Abstract

The goal of this study was to investigate the effects of the sedative drugs midazolam, diazepam, propofol and dexmedetomidine on cell proliferation and vascular endothelial growth factor (VEGF)-induced angiogenesis. The effects of the drugs on cell proliferation and angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to 200 ng/ml of midazolam, 600 ng/ml of diazepam, 3 mg/ml of propofol, or 1 ng/ml of dexmedetomidine (clinically relevant concentrations) for 1, 3, 5 or 10 days in the presence of 10 ng/ml of VEGF. Values are expressed as means ± SE, with statistical analysis performed by ANOVA and Bonferroni-type multiple t-tests. Treatment of HUVECs with 200 ng/ml of midazolam for 10 days and 600 ng/ml of diazepam for 5 or 10 days resulted in significant inhibition of cell proliferation and angiogenesis (P < 0.05, vs. controls), whereas propofol and dexmedetomidine did not inhibit proliferation or angiogenesis over any time period. These results suggest that propofol and dexmedetomidine can be used safely for long term sedation in patients receiving therapeutic angiogenesis for ischemic vascular disease, whereas midazolam and diazepam should not be used, since they may inhibit angiogenesis in these patients.

Key words: Proliferation, angiogenesis, midazolam, diazepam, propofol, dexmedetomidine.