iloprost and Arteriosclerosis-Obliterans

In order to clarify interactions between the various endothelial vasoactive substances, the authors studied the behaviour of endothelin plasma levels during acute iloprost infusion in 7 elderly patients with critical leg ischemia. Iloprost was administered i.v., diluted in saline solution (200 ng/ml, from 30 to 40 ml/h, for 6 hours/day over 4 weeks). Endothelin was assayed in plasma on day 4 of treatment at times 0, 2, 4, 6, 8, hours, or in other words before treatment and ten every 2 hours up until the 6th hour, and then 2 hours after the end of iloprost infusion. The control group consisted of 7 age-matched subjects suffering from peripheral obliterating arterial disease at Fontaine's stage 1 and 2 who where infused with saline solution alone. Patients receiving iloprost presented a mean endothelin plasma level +/- SD at time 0 of 5.40 +/- 1.23 pg/ml, 4.24 +/- 0.72 pg/ml at time 2, 4.22 +/- 0.74 pg/ml at time 4, 4.24 +/- 0.22 pg/ml at time 6, and 4.49 +/- 0.58 pg/ml at time 8. The difference between endothelin levels in basal conditions and those at time 2, 4 and 6 was statistically significant. The difference between the peptide at times 0 and 8 was not statistically significant. In the control group the mean +/- SD of endothelin plasma level was, at the same times, respectively 5.23 +/- 0.55 pg/ml, 4.88 +/- 1.39 pg/ml, 5.44 +/- 1.51 pg/ml, 5.10 +/- 0.86 pg/ml and 5.60 +/- 1.64 pg/ml. The difference between endothelin levels in basal conditions and those at later times was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Aging; Arteriosclerosis Obliterans; Endothelins; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Vasodilator Agents

The traditional medical treatment of atherosclerotic artery disease of the lower limbs with vasodilators, antiplatelet agents, hemorheologic agents and heparin has so far yielded only partly satisfactory results. In view of this, we have treated ten patients with lower limb arterial disease, Fontain stages III and IV, with a stable prostacyclin analogue, iloprost, with antiaggregant, vasodilating, and cytoprotective activity. Patients' mean age 73.6 +/- 9.9 yrs., M/F ratio 9/1. The drug was infused by peristaltic pump at dosages varying from 1.5 to 2 ng/kg body weight/min for 6 hours daily and for an average of 25 days. Our observations, albeit on a limited number of subjects, appear to confirm the good tolerability, and above all the efficacy of iloprost (relative number of patients improved: 0.70). Nevertheless, in our view, a hypertensive diabetic woman who under treatment developed a lower myocardial infarction deserves special attention. Data found in the literature do not allow us to hold iloprost responsible for this effect with any degree of certainty. However, the doubt remains that as a result of its vasodilating action the drug may have caused steal phenomena from the subendocardial to subepicardial districts, thus provoking the ischemic event.

Topics: Aged; Aged, 80 and over; Arteriosclerosis Obliterans; Chronic Disease; Female; Humans; Iloprost; Male; Middle Aged

In a randomized open controlled study the clinical effects and tolerability of prostaglandin E1 (PGE1) and the stable prostacyclin (PGI2) analogue, iloprost in the management of diabetic and non-diabetic patients with advanced peripheral arterial occlusive disease (PAOD Fontaine stage IV) were compared. 267 patients were enrolled in this multicentre study and treated for 21-28 days, either by daily infusions of 6 h with iloprost or 2 x 2 h with PGE1. At the end of treatment patients were assessed for evidence of improvement of trophic lesions, relief of rest pain and change of global clinical status. 228 patients were considered as evaluable for efficacy analysis, which revealed 52.7% responders in the iloprost group and 43.1% for PGE1 (p = 0.148). Whereas iloprost showed similar effects in diabetics and non-diabetics (53.3% and 51.4% response rates, respectively), the diabetics treated with PGE1 had a considerably poorer outcome (36.6% versus 53.3%). At 6 months follow-up 62.2% of patients in both groups were alive with a viable limb. Slightly more iloprost patients underwent major amputation (32.1% versus 27.2%), but the number of deaths was reduced by 50% in the iloprost group compared to the PGE1 group (7.5% versus 14.6%, p = 0.10). Side-effects such as headache, flushing and gastrointestinal symptoms were significantly more common in the iloprost group (73.9%) than in the PGE1 group (31.0%), particularly during the first 3 days of dose titration. No specific toxic or unexpected reactions were reported in either group.

Topics: Adult; Aged; Alprostadil; Arterial Occlusive Diseases; Arteriosclerosis Obliterans; Diabetic Angiopathies; Drug Tolerance; Female; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Peripheral Vascular Diseases

We studied the effects of prostacyclin (PGI2) and its stable analog, iloprost, on blood fibrinolytic activity in 33 patients with peripheral arterial disease. Ten subjects (group A) received three 5-hour infusions of iloprost on three consecutive days. The remaining 23 patients received three different 5-hour infusions (placebo, iloprost 2 ng/kg/min, PGI2 5 ng/kg/min). Tissue plasminogen activator (t-PA), total plasma fibrinolytic activity and euglobulin clot lysis time (ECLT) were determined in patients before and after each infusion, both in freely flowing blood samples and following 10 min venous occlusion. In patients of group A, ECLT at rest was significantly shortened after all three iloprost infusions (on average by about 5-11%). First and third infusions produced also shortening of ECLT after venostasis (by 21 and 32%). Statistically significant rise in t-PA activity (by about 68% on average) accompanied only the first infusion. In patients of the group B iloprost provoked significant fall in ECLT at rest (by about 19% on average) only. PGI2 shortened ECLT both at rest and after venous occlusion (by about 17% and 20% on average, respectively) and led to a rise in t-PA activity after venous occlusion by about 33% on average. Our results indicate that prostacyclin and its stable analog, iloprost, enhance fibrinolytic activity in man by releasing or facilitating the release of tissue plasminogen activator from the vessel wall.

Topics: Adult; Arteriosclerosis Obliterans; Cardiovascular Agents; Epoprostenol; Female; Fibrinogen; Fibrinolysis; Humans; Iloprost; Male; Thromboangiitis Obliterans; Tissue Plasminogen Activator

The aim of this retrospective, study was to assess the tolerance and therapeutic effect of a stable prostacyclin (iloprost) analog in severe forms of permanent lower limb ischemia. Ninety consecutive unselected patients, in Leriche and Fontaine stages III or IV, turned down for vascular surgery after angiography and treated with iloprost for 28 days were enrolled in the study. Patients were followed up clinically (ischemic pain, trophic changes, walking distance) and with transcutaneous oxymetry (D28). Long-term assessment (mean 2 years) was expressed as rates of death, major amputation and "patients alive with limb". There were no manifestations of intolerance to iloprost. At two months, 42 out of 90 patients (47%) were considered as responders because of a lack (n=36) or significant decrease (n=6) in pain, reduction of trophic lesions and conservative walking. At long term (6 months, one and two years) we observed that 10 (11%), 17 (20%) and 22 (25%) patients respectively had died, 24 (27%), 26 (30%) and 28 (32%) patients underwent major amputation, but 60 (68%), 54 (62%) and 49 (56%) patients still alive with their limb and conservative walking. No predictive factors were noted, but diabetic patients without microangiopathy or recent bypass occlusions (respectively 43% and 56% out of patients were alive with limb at 6 months) were associated with bad results. This retrospective study, despite its limitations, underlines the good tolerance to, and effectiveness of iloprost in non surgical chronic critical ischemia. However, no predictive criterion of long-term effectiveness could be established, except initial clinical severity and clinical change one month after treatment.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis Obliterans; Female; Humans; Iloprost; Intermittent Claudication; Ischemia; Leg; Male; Middle Aged; Retrospective Studies; Vasodilator Agents

Iloprost (ZK 36 374), a stable analog of carbaprostacyclin, was infused for 72 h to nine patients with advanced obliterative arterial disease. Iloprost caused a marked vasodilation and a compensatory increase in cardiac output. The glomerular filtration rate increased by 45% and tubular reabsorption of sodium and water were reduced by 80% and 107%, respectively. The urine excretion rate increased by 122%. Tubular handling of potassium and calcium were not influenced by iloprost but magnesium reabsorption was stimulated. The renin-angiotensin system was not activated while serum angiotensin converting enzyme activity was decreased. Kallikrein excretion in urine was increased 4.4-fold but plasma kininogen, a substrate for kallikrein in producing vasoactive kinins, was unaffected by the drug. Plasma levels of 6-keto-PGF1 alpha and TxB2 were decreased and their excretion in urine increased. Plasma catecholamines were not changed by iloprost. Several of the changes persisted for at least the first postinfusion day. The results indicate that iloprost increases urine excretion rate by increasing glomerular blood flow and by inhibiting sodium and water reabsorptions. The kinin-forming system, but not the renin-angiotensin system or plasma catecholamines, may be activated. The decrease in plasma level of prostanoids can be, at least partly, due to their increased excretions in urine.

Topics: Adult; Aged; Arteriosclerosis Obliterans; Catecholamines; Epoprostenol; Female; Glomerular Filtration Rate; Humans; Iloprost; Kallikreins; Kidney; Kinins; Male; Middle Aged; Prostaglandins; Renin-Angiotensin System

Iloprost, a stable analogue of carbaprostacyclin, was infused for 72 h to 9 patients with advanced obliterative arterial disease. Total peripheral and pulmonary vascular resistances and blood pressure were decreased. Cardiac output was elevated with no marked extra cardiac load. The glomerular filtration rate was increased and tubular reabsorption of sodium and water reduced. Consequently, urine excretion increased. The renin-angiotensin system was not activated but excretion of renal kallikrein was augmented. Several patients showed clinical improvement. The drug was well tolerated except for gastrointestinal side-effects with the dose of 4 ng X kg-1 X min-1 or more.

Topics: Adult; Arteriosclerosis Obliterans; Blood Pressure; Cardiac Output; Cardiovascular Agents; Epoprostenol; Female; Glomerular Filtration Rate; Humans; Iloprost; Kallikreins; Kidney; Male; Middle Aged; Pulmonary Circulation; Vascular Resistance

Topics: Aged; Arteriosclerosis Obliterans; Cardiovascular Agents; Drug Evaluation; Epoprostenol; Female; Humans; Iloprost; Infusions, Parenteral; Leg; Male; Middle Aged; Prospective Studies