Effects of ketanserin, a 5-HT2-receptor antagonist, on the blood flow response to temperature changes in the diabetic foot.

We studied the effect of ketanserin, a relatively specific antagonist for 5-hydroxytryptamine2-serotonergic receptors, on the total blood flow to the foot of patients with diabetes using a computerized pulse volume plethysmograph and a temperature controlled foot chamber. Ketanserin was administered intravenously as a bolus of 10 mg over four minutes followed by a constant infusion at the rate of 5 mg/hr. Saline infusion served as a control in each subject. Sixteen patients with type II diabetes and two patients with type I diabetes were studied. Mean age was 58.5 +/- 1.6 years and mean duration of diabetes was 10 +/- 2 years. Basal blood flow (mean +/- SEM, mL/100 mL/min) at room temperature was 3.77 +/- 0.99 with saline and 12.07 +/- 1.81 with ketanserin. At 38 to 40 degrees C, the values were 4.84 +/- 1.09 and 16.93 +/- 1.83. Reactive hyperemia was measured following three minutes of arterial occlusion; at 38 to 40 degrees C the flow rate was 20.67 +/- 2.45 with saline and 30.86 +/- 3.02 with ketanserin, while at 8 to 10 degrees C the corresponding values were 15.63 +/- 2.01 and 27.16 +/- 2.03. All differences between saline and ketanserin had a P less than .01. Venous distensibility (vol% at 50 mm Hg) at 8 to 10 degrees C was 0.55 +/- 0.05 with saline and 0.90 +/- 0.15 with ketanserin, P less than .05. Our findings are consistent with the hypothesis that serotonin is involved in the limitation of blood flow to the foot in diabetes and that ketanserin may play a potential role in therapy.