The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)

Dipyridamole has been reformulated to guarantee systemic bioavailability and steady state
levels compatible with inhibition of platelet aggregation ex vivo (1). This newly
formulated dipyridamole has been shown to roughly equal in efficacy to low dose aspirin in
the secondary prevention of stroke and the drug combination seems roughly additive (2). The
present study is designed to explore two potential mechanisms which have been linked to
dipyridamole action on the vessel wall; modulation of vascular eicosanoid generation and
prevention of oxidant stress (3). We shall address the hypothesis that dipyridamole affects
these systems in patients with PAD. These individuals have disordered platelet-vascular
interactions, as reflected by increased generation of thromboxane, an index of platelet
activation and of prostacyclin, probably a homeostatic response to traumatic and chemical
stimulation of the endothelium (4,5). Furthermore, we shall assess the functional
consequences of dipyridamole action, alone and in combination with aspirin compared with
aspirin alone on local measurements of flow and oxygenation, including exercise tolerance,
Doppler Ultrasound and Near Infrared Spectroscopy (NIRS). Lipid peroxidation will be
quantified based on mass spectrometric analysis of the major urinary isoprostane,
8,12-iso-iPF2a-VI (6,7).