Microcirculatory Effects of Iloprost in Patients with Suspected Secondary Raynaud Phenomenon

Abstract

Background: The clinical efficacy of iloprost, a stable analogue of prostacyclin, in patients with Raynaud's phenomenon (RP) has been widely reported. However, its mechanism of action is still unclear, and also unknown is why the benefit lasts for many weeks after therapy is discontinued. The aim of the present study was to learn what kind of microcirculatory changes occur in the skin of the affected hand one month after the end of iloprost treatment in patients with RP. Patients and Methods: Eleven subjects (8 women, 3 men, mean age forty-four years) with RP suspected to be secondary to a collagen disease entered the study and were infused with iloprost up to 2.0 ng/kg/minute for six hours on five consecutive days. At baseline and one month after treatment discontinuation, laser Doppler flowmetry, thermography, and computer-assisted video capillaroscopy of the affected hand were performed. Results: At the end of follow-up, the mean capillary density as recorded by video capillaroscopy was significantly increased as was the skin temperature in the different areas (fingertip, nailbed, tenar, hypotenar). In contrast, laser Doppler flowmetry revealed no significant changes after therapy. Comment: The improvement of vascularization of the skin and, therefore, the decrease in avascular areas in patients with RP suspected to be secondary to a connective tissue disease appear to be associated with enhancement of nutritional flow. Rather than rely on an angiogenetic effect of iloprost, these modifications may be related to the drug-induced normalization of the described dysfunctional arteriolar-venular anastomoses in the skin of RP patients through redistribution of flow.

Effects of iloprost, either administered for 1 week or 4 weeks, on systemic hemodynamics, peripheral blood flow, and exercise tolerance in patients with peripheral occlusive arterial disease at leriche-fontaine stage III

“…However, the different duration of the daily infusions should have been made impossible, from both ethical and practical points of view, to realize blindness. Furthermore, on the one hand, the changes observed in clinical parameters are consistent with data published for similar patient populations treated with iloprost [12,23,24]. On the other hand, the actual comparison between the two dose regimens, through a limited number of exercise tests and multiple hemodynamic parameters, could have balanced any placebo or training effect.…”

“…Iloprost is a synthetic prostacyclin analogue with pharmacological effects similar to those of the natural prostacyclin [1,2] but with a greater chemical stability and a more favorable therapeutic index which allows its clinical use in diseases, such as severe leg ischemia, Raynaud's phenomenon, thromboangiitis obliterans, and primary pulmonary hypertension [3][4][5]26]. Many pharmacological effects of iloprost have been demonstrated in either animal or man: inhibition of platelet aggregation, blockade of leukocyte migration, tissue protection, vasodilation, profibrinolytic effect, and neuronalsynaptic effect [1,[6][7][8][9][10][11][12]. Besides the different relevance of each effect, depending on the clinical indication, the threshold dose for each effect seems to differ substantially.…”

Long-term cyclic intravenous iloprost in systemic sclerosis: clinical experience from a single center

“…This molecule, besides having a vasodilatory action on numerous body areas, also determines important modulation of the immune system and of fibrosis through mechanisms which are still only partly understood (11). Among these is the increase in nitric oxide bioavailability, the reduction of which increases endothelin levels, antiplatelet action, reduced expression of adhesion molecules (VCAM-1, ICAM-1, VEGF, E-selectin), inhibition of some fibrogenetic cytokines (TGF-beta, CTGF) (12)(13)(14). The aim of the present study was to analyze the medical records of patients with sclerodermia undergoing long-term cyclic treatment with iloprost to identify clinical and therapeutic factors correlated with therapy.…”