Potential therapeutic mechanisms of stable prostacyclin (PGI2)-mimetics in severe peripheral vascular disease.
In 2 randomized, double-blind studies, 109 diabetic patients with trophic lesions and 101 non-diabetics suffering from peripheral vascular disease (PVD) stage IV (Fontaine) received daily 6-hour i.v. infusions of iloprost (less than or equal to 2ng/kg/min) or of placebo over 28 days. Iloprost treatment was superior to placebo, showing ulcer healing in more than 60% of patients compared to less than 25% in the control group. The beneficial effects were sustained during a 1 year follow-up period. Platelet activation, adhesion, aggregation and release reaction on atherosclerotic lesions, impaired microvascular perfusion, loss of microvascular barrier function, increased white blood cell - vessel wall interaction and hemorheological disturbances are all believed to play a role in PVD. Stable PGI2-mimetics inhibit platelet activation by all endogenous mediators as well as platelet release of mitogenic factors (PDGF).
Müller
B
B
Institute of Pharmacology, Research Laboratories of Schering AG Berlin (West), FRG.
Krais
T
T
Stürzebecher
S
S
Witt
W
W
Schillinger
E
E
Baldus
B
B
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D016285:Iloprost; D007262:Infusions, Intravenous; D008833:Microcirculation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D013927:Thrombosis / Q000188:drug therapy*; D014456:Ulcer / Q000188:drug therapy*; D014652:Vascular Diseases / Q000188:drug therapy*
D002317:Cardiovascular Agents; D011464:Epoprostenol; D016285:Iloprost