Effects of intravenous prostaglandin E1 on arterial compliance: a randomized controlled trial.
BACKGROUND
Prostanoids are in widespread use for the treatment of critical limb ischemia and are suggested to improve arterial compliance. However, dose- and time-dependency of these drug effects are indeterminate. We investigated the influence of intravenous application of prostanoids on arterial compliance parameters in patients with critical limb ischemia due to peripheral artery disease (PAD).


METHODS
We included 82 consecutive patients with PAD Fontaine stage III and IV in a patient-blinded, randomized controlled trial. Patients were randomly assigned to either single dose intravenous treatment with 40 microg (n = 29) or 60 microg (n = 27) of Alprostadil (PGE1) in 250 ml 0.9% saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26). Large and small artery compliance was measured by peripheral pulse contour analysis at baseline, at one hour during intravenous infusion of Alprostadil, immediately after and 24 hours after the end of the infusion. For study purposes the patients received Alprostadil only once during the observation period of 2 days.


RESULTS
Large artery compliance, blood pressure, heart rate and cardiac output were unaffected by PGE1 administration irrespectively of drug-dosage or time interval. Small artery compliance increased at 1 hour during intravenous application of Alprostadil (40 microg Alprostadil p = 0.001; 60 microg Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to +100%) after administration of 40 microg Alprostadil and median +32% (IQR -11% to +88%) after 60 microg Alprostadil (p = 0.5). Immediately after the end of Alprostadil infusion small artery compliance decreased to baseline levels.


CONCLUSIONS
Prostaglandin E1 causes a significant improvement of small artery compliance during the time of intravenous application. However, this effect rapidly diminishes after the end of administration and no dose-dependency between 40 microg and 60 microg Alprostadil is observed.
Department of Angiology, Vienna General Hospital, Medical School, Austria. wolfgang.mlekusch@akh-wien.ac.at
W
W
Mlekusch
M
M
Schillinger
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S
Sabeti
M
M
Al-Awami
M
M
Gschwandtner
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E
Minar
D000222:Adaptation, Physiological / Q000187:drug effects; D000368:Aged; D000527:Alprostadil / Q000008:administration & dosage*; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D016896:Treatment Outcome; D018924:Vascular Capacitance / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
D014665:Vasodilator Agents; D000527:Alprostadil