Effect of iloprost on plasma asymmetric dimethylarginine and plasma and platelet serotonin in patients with peripheral arterial occlusive disease.
BACKGROUND
Iloprost, a prostacyclin analogue, is used in the treatment of peripheral arterial occlusive disease at Leriche-Fontaine stages III-IV, through intravenous infusion for at least 21 days. Recently, iloprost has been shown to be safe and effective in critical limb ischemia patients when administered per 7 days. We investigated in patients at Leriche-Fontaine stages III-IV the effect of 1-week treatment with iloprost on plasma asymmetric dimethylarginine (ADMA), plasma and platelet serotonin, and on clinical response.


RESULTS
Twenty-four critical limb ischemia patients (16 men and 8 women, mean age 76+/-9.7 years) were included in the study and treated with intravenous iloprost (titrated from 0.5 up to 1.5 ng/kg/min) for 16 h a day for seven consecutive days. Blood samples were drawn before infusion on days 1, 4 and 8 of treatment, under the same conditions. Clinical assessment was performed by clinical evaluation, ankle/brachial pressure index and treadmill exercise test. During treatment with iloprost patients clinically improved and plasma levels of ADMA significantly decreased (p<0.001). We also observed a significant increase of serotonin (p<0.01) in platelets and a significant decrease of serotonin (p<0.001) in plasma. Similar variations of ADMA and serotonin were found in two subgroups of patients, diabetics and non-diabetics.


CONCLUSIONS
One-week treatment with iloprost in critical limb ischemia patients induced changes of peripheral markers of endothelial dysfunction and atherosclerosis, such as ADMA and serotonin, associated to a clinical improvement.
Blardi
Patrizia
P
Center of Clinical Pharmacology, University of Siena, Italy. blardi@unisi.it
de Lalla
Arianna
A
Pieragalli
Daniela
D
De Franco
Vincenzo
V
Meini
Simone
S
Ceccatelli
Linda
L
Auteri
Alberto
A
D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D004334:Drug Administration Schedule; D005080:Exercise Test; D005260:Female; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012701:Serotonin / Q000097:blood*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; C018524:N,N-dimethylarginine; D001120:Arginine; D016285:Iloprost