Atherosclerosis, peripheral arterial disease and the vascular response to ketanserin

Platelet activation releases thromboxane A2 and serotonin, which acts on blood vessels through a specific, 5-hydroxytryptamine (5-HT2) receptor. The development of ketanserin, the selective 5HT2 receptor blocker, has made it possible to explore the role of serotonin in patients with advanced atherosclerotic disease. Ketanserin in low doses (3 to 30 micrograms/kg) was administered intra-arterially to 23 patients with symptomatic peripheral occlusive vascular disease during peripheral angiography: an additional seven patients received a placebo. The angiographic response was evaluated by coded reading and by computer-assisted measurement of arterial segments in four anatomical regions (pelvis, thigh, knee, and lower leg). Hemodynamic changes were assessed by mercury strain gauge plethysmography and Doppler pressure measurement. Unequivocal vasodilatation was observed in zero of seven placebo-treated patients and in 13 of 23 (57%) treated patients primarily at the level of collateral vessels. Dilation of the geniculate arteries, a major source of collaterals to the calf, was associated with a significant increase in the blood flow delivery to the calf. There was a moderate drop of systemic blood pressure in patients who failed to respond with peripheral vasodilatation. Ketanserin induces hemodynamically significant vasodilatation in some patients with peripheral vascular disease, suggesting that serotonin may contribute to ischemia in some patients with advanced atherosclerosis.