Effects of Ketanserin, a 5-HT2-Receptor Antagonist, on the Blood Flow Response to Temperature Changes in the Diabetic Foot

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Abstract
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°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°C the flow rate was 20.67 ± 2.45 with saline and 30.86 ± 3.02 with ketanserin, while at 8 to 10°C the corresponding values were 15.63 ± 2.01 and 27.16 ± 2.03. All differences between saline and ketanserin had a P < .01. Venous distensibility (vol% at 50 mm Hg) at 8 to 10°C was 0.55 ± 0.05 with saline and 0.90 ± 0.15 with ketanserin, P < .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.