Dose responsive suppression of myointimal hyperplasia by dexamethasone

Abstract

The effect of increasing doses of dexamethasone on the development of myointimal hyperplasia in the rabbit carotid artery was studied by use of a balloon catheter injury model. Seventy New Zealand white rabbits underwent a standardized 2F balloon catheter stripping of the left carotid intima. The animals were randomly assigned to one of seven groups, each receiving daily injections of either saline (group I, N = 10) or graded doses of dexamethasone: 0.025 mg/kg (group II, N = 10); 0.050 mg/kg (group II, N = 10); 0.075 mg/kg (group IV, N = 10); 0.100 mg/kg (group V, N = 10); 0.125 mg/kg (group VI, N = 10); 0.150 mg/kg (group VII, N = 10). Injections were started 2 days before the intimal injury and continued daily, five times a week, for 8 weeks. The vessels were harvested 12 weeks after injury, and the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina was measured as an index of myointimal hyperplasia. Also, at the time of harvest, blood flow (ml/min) was measured and the resistance ΔP/flow (mm Hg/ml/min) calculated for each vessel in vivo. Twelve-week patency rates were 60% in the control group I, 90% in groups II and III, and 100% in groups IV, V, VI, and VII. The value for the intimal hyperplasia/internal elastic lamina index, expressed as a percent, was 22.2 ± 3.7 for control group I, 17.7 ± 2.1 group II, 14.8 ± 3.0 group III, 12.8 ± 2.4 group IV, 11.5 ± 1.8 group V, 5.4 ± 1.3 group VI, and 3.9 ± 1.1 for group VII. The calculated values for the ΔP/flow in mm Hg/ml/min were 51.6 ± 3.7, 47.4 ± 4.5, 19.3 ± 6.7, 20.2 ± 7.4, 6.2 ± 4.1, 5.1 ± 1.9, and 8.3 ± 6.5 for groups I to VII, respectively. The observed decrease in the intimal hyperplasia/interval elastic lamina index by dexamethasone is dose related. The lowest dose at which this decrease reaches statistical significance, compared with control, is group III (0.050 mg/kg,p < 0.05). In addition, this observed reduction in myointimal hyperplasia, by histologic criteria, is reflected by an improvement in the measured hemodynamic parameters. Again, the studied dose at which the measured in vivo parameters reach statistical significance is 0.050 mg/kg. We conclude that in the rabbit, dexamethasone is effective in suppressing the hyperplastic myointimal reaction to an intimal injury and that this response is dose dependent. In addition, the minimal effective dose required to achieve this effect is 0.050 mg/kg, and no further significant improvement is noted above 0.125 mg/kg.