iloprost and Arterial-Occlusive-Diseases

The use of Iloprost in the treatment of critical leg ischemia in very old patients can lead to tolerability problems, related to the drug used and to the kind of patient treated. The aim of this study was to evaluate the impact of this therapy on the activities of daily living and on the quality of life of the patient together with its efficacy and tolerability.. We studied 20 subjects (mean age 74 +/- 6.8) divided in 2 groups homogeneous for age, seriousness of the disease and presence of diabetes mellitus. In the first group Iloprost was administered for 6 hours, for 28 consecutive days, in the second group for 6 hours, two times a day for 14 consecutive days. In each group we observed the following parameters before and after treatment: clinical evaluation of pain and use of analgesics, ADL and SK39 questionnaire, ankle/arm index c.w. Doppler, strain gauge plethismography of lower limbs, TcPO2 at the back-feet level.. Treatment was well tolerated in both groups where we observed a similar reduction of pain, a reduction in the instrumental indexes which express the microcirculatory activity, an improvement in the quality of life and in the capacity to carry out everyday activities. The double daily administration of Iloprost did not cause any significant side effect in the subjects studied, and a better responsiveness to the pain symptomatology was observed.. Iloprost can be used in the treatment of critical leg ischemia even for very old patients with good tolerability and effectiveness. In the double daily administration no relevant side effect was observed. This approach is to be preferred also in terms of cost-effectiveness.

Topics: Activities of Daily Living; Age Factors; Aged; Aging; Arterial Occlusive Diseases; Female; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Platelet Aggregation Inhibitors; Quality of Life; Thrombolytic Therapy; Treatment Outcome

Topics: Angiography; Arterial Occlusive Diseases; Arteriosclerosis; Cilostazol; Clinical Trials as Topic; Clopidogrel; Endothelial Growth Factors; Genetic Therapy; Humans; Iloprost; Leg; Lymphokines; Multicenter Studies as Topic; Phosphodiesterase Inhibitors; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Protein Isoforms; Randomized Controlled Trials as Topic; Tetrazoles; Ticlopidine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vasodilator Agents

Topics: Alprostadil; Arterial Occlusive Diseases; Aspirin; Bandages; Electric Stimulation Therapy; Exercise Therapy; Humans; Iloprost; Infections; Leg Ulcer; Pain Management; Risk Factors; Spinal Cord; Vascular Surgical Procedures; Venous Insufficiency; Walking

The authors report the observation of a 31-year-old woman who presented with total occlusion of digestive arteries and was successfully treated pharmacologically. A review of the literature shows that digestive arteries thrombosis is a rare condition in young women. Only 15 cases have been previously reported. Prognosis was poor with a mortality rate of 71%; 93% used oral contraception and more than 50% were smokers. All these cases were curiously similar. The authors accentuate the role of iloprost in the recovery of the patient. Digestive artery occlusion should be taken into consideration in the differential diagnosis of abdominal pain, especially in young women who smoke and take estrogen-containing birth control pills.

Topics: Adult; Arterial Occlusive Diseases; Celiac Plexus; Female; Humans; Iloprost; Mesenteric Arteries; Mesenteric Vascular Occlusion; Vasodilator Agents

Prostacyclins (PGl2) inhibit platelet-platelet interactions at concentrations that do not affect platelet adhesion to collagen and other arterial subendothelial structures exposed during injury. Such compounds can be encapsulated within platelets by reversible electroporation and, using the platelet's natural haemostatic propensity, they can be targeted to injured vessels in vivo. In rat (aorta), rabbit (ileofemoral) and pig (carotid) angioplasty models, autologous platelets, electro-loaded with the stable prostacyclin iloprost and given intravenously after balloon overstretch injury, substantially reduced platelet deposition at the lesion site as compared with control platelets. In the pig model, when the drug-loaded platelets were delivered directly to the injury site during angioplasty via a double balloon delivery catheter, platelet deposition was restricted to monolayer coverage (> 80% reduction compared with controls). Candidate antiproliferative drugs (for co-encapsulating with iloprost) are being investigated in order to develop a combined antithrombotic/antirestenosis strategy for use during angioplasty and thrombolysis procedures. Autologous platelets as drug-targeting vehicles should obviate many of the immunological, toxicological and biodegradability concerns inherent in the use of other drug transport vectors such as antibodies, viruses, liposomes and synthetic polymer microcapsules.

Topics: Angioplasty, Balloon; Animals; Arterial Occlusive Diseases; Arteries; Blood Platelets; Drug Carriers; Drug Delivery Systems; Humans; Iloprost; Infusions, Intravenous; Platelet Aggregation Inhibitors; Postoperative Complications; Rabbits; Rats; Swine; Thrombosis

In patients with Fontaine Stage III and IV POAD unsuitable for arterial reconstruction, Iloprost, a prostacyclin analogue, has been shown in six RCTs to have a significant (p < 0.05) beneficial effect with regards to the probability of being alive with both legs at six months follow-up. Iloprost has significant (p < 0.05) beneficial effects over placebo on ulcer healing and pain relief, but these were relatively soft endpoints to study when side effects may have unblinded many observers and patients. Further studies are indicated to investigate the possible benefit of repeated courses of treatment with Iloprost in patients with non-reconstructable Fontaine Stage III and IV POAD as well as studies looking at patients who may be suitable only for relatively high risk reconstructions. Meta-analysis of all other RCTs of pharmacotherapeutic agents in patients with Fontaine Stage III and IV POAD showed no significant benefit over placebo for any of the endpoints reported.

Topics: Alprostadil; Amputation, Surgical; Ancrod; Arterial Occlusive Diseases; Epoprostenol; Humans; Iloprost; Nafronyl; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Survival Analysis

Topics: Arterial Occlusive Diseases; Blood Platelets; Cell Adhesion; Clinical Trials as Topic; Endothelium, Vascular; Humans; Iloprost; Leukocytes; Microcirculation; Thrombosis

This study is planned bringing about a new choice for the prophylaxis of RA spasm which is topical iloprost and compares its efficacy with papaverine and diltiazem.. Twenty eight CABG patients with RA grafts were categorized into four groups by taking into account the topical vasodilator (papaverine, diltiazem, iloprost and saline) that was utilized during harvesting. Arterial segments were separated into four rings and were than soaked with KCL, norepinephrine, phenylephrine and serotonin. Then, acetylcholine was given to induce relaxation and the preparations were put to rest for 10 minute.. The contraction response achieved by the vasoreactive agents was most effectively inhibited by papaverine. The effectiveness of the response obtained by iloprost was similar to that of papaverine and significantly stronger than that of diltiazem. Especially at high vasoreactive substance concentrations, diltiazem had a contraction close to that of the control while the protective effect was weaker than those of papaverine and iloprost.. Iloprost can be recommended as a strong alternative to the topical agents used for preventing arterial graft spasm.

Topics: Administration, Topical; Aged; Arterial Occlusive Diseases; Coronary Artery Bypass; Diltiazem; Dose-Response Relationship, Drug; Female; Graft Occlusion, Vascular; Humans; Iloprost; Male; Middle Aged; Norepinephrine; Papaverine; Phenylephrine; Potassium Chloride; Radial Artery; Serotonin; Spasm; Tissue and Organ Harvesting; Treatment Outcome; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Arginine; Arterial Occlusive Diseases; Blood Platelets; Blood Pressure; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exercise Test; Female; Humans; Iloprost; Infusions, Intravenous; Male; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Serotonin; Treatment Outcome

A prospective, randomised study was undertaken to investigate the effect of intravenous infusion of either iloprost, the stable prostacyclin (PGI2) analogue, or alprostadil (prostaglandin E1) on peripheral resistance (PR) during femoro-distal reconstruction.. A prospective randomised study was performed with 35 patients. The PR Measurement of peripheral resistance involved a silicon tube temporarily inserted between the donor and recipient vessel. A flowmeter probe and a pressure transducer were inserted into the tube. The peripheral resistance was calculated as a quotient of pressure and flow under approximate physiological conditions. Patients received either alprostadil (4.4 ng/min/kg) or iloprost (2 ng/min/kg) intravenously over ten minutes. After the end of the infusion, the measurements were taken for five minutes.. Baseline peripheral resistance was similar for both groups (iloprost 0.76+/-0.54 mmHg/ml/min, alprostadil 0.72+/-0.35 mmHg/ml/min, p>0.05). Following the measurement procedure, the final peripheral resistance in the iloprost group was reduced (0.57+/-0.33 mmHg/ml/min), but the difference to the alprostadil group (0.70+/-0.36 mmHg/ml/min) was not significant (p>0.05). The different decrease of ratio peripheral resistance (quotient between final and baseline resistance times one hundred) was highly significant (iloprost: 79.4+/-13.4% vs alprostadil: 97.0+/-15.6%, p<0.01).. Intravenous application of prostanoids, infused with usual doses over ten minutes during femoro-distal reconstructions, produces significant differences in decrease of peripheral resistance. Alprostadil only causes a slight drop of resistance, whereas iloprost causes a significant higher reduction of peripheral resistance.

Topics: Adult; Aged; Aged, 80 and over; Alprostadil; Arterial Occlusive Diseases; Blood Vessel Prosthesis; Female; Femoral Artery; Fibrinolytic Agents; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Plastic Surgery Procedures; Platelet Aggregation Inhibitors; Prospective Studies; Vascular Resistance; Vasodilator Agents

Endothelial vascular tone modulators are thought to be involved in aetiopathogenesis of systemic sclerosis (SS) and of peripheral artery occlusive disease (PAOD). Iloprost, a prostacyclin (PGI2) analogue, induces clinical benefit in patients suffering from peripheral ischaemia. This study was performed to investigate the effect of this drug on endothelial function in vivo to elucidate the role of vascular tone modulators.. Fourteen PAOD and 15 SS patients were treated for 24 and 10 days respectively. On the first day, before and after therapy, nitric oxide metabolites (NO2-/NO3-) and endothelin-1 (ET-1) plasma concentrations were detected; moreover, the endothelium-dependent vasodilatation in response to artificial ischaemia was evaluated by means of an echo-Doppler device.. The echo-Doppler evaluation showed that the percentage of arterial reactive dilatation was not modified by placebo or by iloprost, and that the increase in blood velocity flow lasted for a significant longer time after drug infusion (226.79 +/- 17.49 vs. 310.71 +/- 36.32 s; P > 0.04). NO2-/NO3- and ET-1 plasma concentration were higher in patients than in control subjects (P < 0.004). After 6 h of iloprost infusion, no significant modifications were detected.. This study provides evidence that iloprost enhances the microvascular functional capacity and clinical benefit for patients. The effects of the drug seem to be independently or not directly correlated with its interactions with vascular tone modulators such as NO2-/NO3- or ET-1.

Topics: Adult; Aged; Arterial Occlusive Diseases; Chronic Disease; Endothelin-1; Endothelium, Vascular; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Microcirculation; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Scleroderma, Systemic; Ultrasonography; Vasodilator Agents

The effects of 14-day physical exercise or iloprost treatment (0.5-2 ng/Kg/min) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease (Fontaine Stage II). Peripheral venous blood samples and 4-h urine samples were collected before, immediately after 14 days of therapy and 7-10 days after therapy in order to evaluate neutrophil adhesion, nitrite/nitrate and cGMP excretion rates. A longer pain free walking distance was observed after exercise, compared to iloprost (>500 m in 3/10 subjects). Urinary nitrite/nitrate, as well as cGMP concentrations, significantly increased after exercise. Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion. No variations were observed in these parameters in iloprost treated patients. The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise. The results from the present and previous observations indicate that, besides pharmacological treatments, a regular aerobic exercise improves peripheral arterial occlusive disease.

Topics: Aged; Arterial Occlusive Diseases; Cell Adhesion; Exercise Therapy; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Neutrophil Activation; Neutrophils; Nitrates; Nitric Oxide; Nitrites; Peripheral Vascular Diseases; Vasodilator Agents

Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/min has been shown in patients with PAOD III/IV to significantly improve healing of trophic lesions, relief of rest pain, and reduce the rate of major amputation or death at 6 months as compared to placebo. The effect is considered related to improvement of the microcirculation. The aim of the present trial was to identify an optimum dose regarding treatment response and tolerability, by studying 4 doses of 25, 50, 75 and 100 micrograms iloprost daily.. 302 patients with PAOD IV were randomised via a double-blind fashion to one of the 4 doses. The primary endpoint was the responder rate at end of treatment. Responders were defined as patients with very good or good global efficacy, as judged by lesion healing and pain relief. Side effects were documented and a pre-defined benefit/risk index was calculated.. No dose-dependency of iloprost regarding primary or secondary endpoints was observed. The rate of responders ranged between 48.7-53.5%. Side effects, mainly related to vasodilation, increased dose-dependently (p < 0.001, chi 2-test), with a significant decrease of the benefit/risk index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA). Responders had a better outcome at 6 months than non-responders (2.6 fold higher rate of major amputation or death; life table analysis).. It is concluded that iloprost should be titrated to the optimum rather than maximum tolerated dose, since a higher incidence of side effects not associated with an increased treatment response was observed at higher doses.

Topics: Aged; Aged, 80 and over; Arterial Occlusive Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Microcirculation; Middle Aged; Treatment Outcome; Vasodilator Agents

Intra-graft injection of the prostacyclin analogue, iloprost, was performed at the end of femorodistal bypass procedures in 12 patients with severe peripheral arterial occlusive disease. Iloprost plasma levels were measured and compared with changes in haemodynamics. There was a high initial iloprost plasma level (mean 625 pg/ml) which dropped to a mean of 50 pg/ml after 15 min. This correlated with an immediate reduction in systolic blood pressure which had returned to pretreatment levels after 15 min. In contrast, the vascular resistance distal to the graft showed a reduction after 5 min which was maintained for at least 20 min after iloprost injection and the mean blood flow through the graft increased steadily throughout the same period of measurement. The study showed an effect of iloprost on blood pressure which correlated with plasma levels, but the time course of the changes in distal vascular resistance and graft blood flow demonstrated an effect more prolonged than the half-life of iloprost.

Topics: Aged; Arterial Occlusive Diseases; Blood Pressure; Female; Femoral Artery; Half-Life; Hemodynamics; Humans; Iloprost; Male; Middle Aged; Veins

To investigate the effects of two platelet inhibitors, aspirin and iloprost, on platelet uptake and restenosis at the site of angioplasty in patients undergoing femoral or popliteal angioplasty.. Prospective, open, randomised group comparison.. Two university hospitals.. 43 patients undergoing femoral or popliteal angioplasty were randomised.. Patients received either aspirin (300 mg/day), iloprost (8 hours/day i.v. infusion) or no antiplatelet medication during angioplasty and on the subsequent two days.. Platelet uptake was measured using 111Indium-labelled platelets. Restenosis was assessed by repeat angiography at 3 months and clinical symptoms up to 12 months.. Median changes in platelet uptake were similar in the three treatment groups, but all platelet radioactivity ratios > 2.0 occurred in the control group. Restenosis at 3 months was observed in 3 control, 5 aspirin and 1 iloprost patient. Further surgical intervention was performed in 3 control and 3 aspirin patients, but in none of the iloprost patients up to 12 months after angioplasty.. Antiplatelet therapy may prevent large increases in platelet deposition at the angioplasty site, but the link between platelet deposition and restenosis was not substantiated in this study.

Topics: Aged; Angioplasty, Balloon; Arterial Occlusive Diseases; Aspirin; Constriction, Pathologic; Female; Femoral Artery; Humans; Iloprost; Indium Radioisotopes; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Popliteal Artery; Prospective Studies; Recurrence

The flux distribution within ischemic ulcers and adjacent skin and its change by prostanoids was investigated using laser Doppler flux scanning. A prostanoid-induced increase in ulcer flux could be a rationale for the improved wound healing. In a single-blind prospective study 18 patients received prostaglandin E1 (PGE1) (333.3 ng/min.), iloprost (41.7 ng/min final dose), and 0.9% saline in a randomized order. The average laser Doppler flux within the ulcer (LFU, x +/- SEM, arbitrary units) or in the adjacent skin (LFS) was evaluated before and 30, 60, 90, and 120 min after prostanoid/saline infusion. LFU increased with PGE1 from 2.30 +/- 0.27 to 3.08 +/- 0.31 (+33.9%; P < 0.001) and with iloprost from 2.37 +/- 0.26 to 3.03 +/- 0.27 (+27.8%; P < 0.001) after 120 min, respectively. Saline did not change LFU significantly: 2.19 +/- 0.18 vs 2.55 +/- 0.26 (+16.4%; P > 0.05). Simultaneously, LFS was not significantly changed when pretreatment values were compared with mean flux at 120 min: PGE1 2.13 +/- 0.27 vs 2.54 +/- 0.34, iloprost 2.03 +/- 0.26 vs 1.94 +/- 0.21, and saline 1.74 +/- 0.27 vs 1.92 +/- 0.30 (P > 0.05, each), respectively. The laser Doppler flux scanning technique might be a tool to study the distribution of laser Doppler flux within ischemic ulcers. This might be useful to study the physiological or pathophysiological control of flux within ischemic ulcers as well as possible therapeutic approaches.

Topics: Adult; Aged; Alprostadil; Arterial Occlusive Diseases; Cross-Over Studies; Female; Foot Ulcer; Humans; Iloprost; Ischemia; Laser-Doppler Flowmetry; Leg; Leg Ulcer; Male; Middle Aged; Ultrasonography; Vasodilator Agents

In an open study the clinical efficacy and tolerability of the stable prostacyclin (PGI2) analogue iloprost in the treatment of 900 patients with advanced peripheral arterial occlusive disease (Fontaine stage III and IV), enrolled by 169 centres, were investigated. Of these patients, treated with infusions over 6 h daily up to 42 days, 853 could be evaluated: four were excluded because of wrong diagnosis. The responder rates, defined as pain relief, no or reduced use of analgesics (stage III and IV), improvement of trophic lesions, i.e. complete or > or = 50% healing of ulcers, demarcation of necroses (stage IV), and global improvement, were 75.0% and 66.0% in stage III and 46.3% and 41.8% in stage IV patients in the valid case and intention-to-treat group, respectively. A complete healing of ulcers was observed in 12.3% of those patients (n = 375) presenting with ulcerations at the beginning of treatment. Diabetic and non-diabetic patients were comparable with regard to efficacy of iloprost. 71.4% and 66.2% (stage III and IV) of initial responders at 6 months follow-up were still free from rest pain and showing complete or partial healing of trophic lesions. 7.9% of stage III and 16.9% of stage IV patients underwent major amputation during the whole study period with a reduced amputation rate in responders compared to non-responders in stage IV. 7.9% stage III and 13.2% stage IV patients died. 83.2% and 86.0% of stage III and IV patients presented with adverse events at any time of treatment, mainly headache, nausea and flush as well as gastrointestinal symptoms, occurring mostly during the titration phase. The investigators' judgement, however, revealed a very good and good tolerability in 74.8% of stage III and in 73.7% of stage IV patients.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Arterial Occlusive Diseases; Female; Humans; Iloprost; Infusions, Intravenous; Leukocyte Count; Male; Middle Aged; Pain; Platelet Aggregation Inhibitors; Risk Factors; Treatment Outcome; Vasodilator Agents

This study has been designed to demonstrate the in vivo effects of iloprost therapy on expression of adhesion molecules on phagocytes. Sixty patients suffering from peripheral arterial occlusive disease (PAOD) and/or from skin ulcers due to secondary progressive systemic sclerosis (PSS) were enrolled in a double-blind controlled parallel study. Thirty patients (group I) underwent iloprost infusion and 30 patients (group II) were treated with aspirin. Clinical assessment and measurement of phagocyte activation in vivo, using quantitative flow cytometry, were performed on entry and after 6 h on the first day of therapy. After 3 months of therapy, complete healing of all cutaneous lesions was observed in 84% of the patients treated with iloprost compared with the control patients (P < 0.001). Neutrophils and monocytes of PAOD and PSS patients showed a significant decrease in the expression of the alpha M beta 2 integrin adhesion receptor after 6 h of iloprost infusion. Neutrophils and monocytes released a lower amount of anion superoxide (O2-) after 6 h of iloprost treatment. These data confirm other clinical observations but demonstrate that in vivo this drug modifies the expression of the alpha M beta 2 integrin of phagocytes that has a key role in leukocyte-endothelium interactions in cases of inflammation and thrombosis.

Topics: Adult; Aged; Arterial Occlusive Diseases; Double-Blind Method; Female; Humans; Iloprost; Macrophage-1 Antigen; Male; Middle Aged; Phagocytes; Scleroderma, Systemic; Skin Temperature

The effect of intravenous therapy with iloprost (average duration 6 weeks) on the prognosis of leg-preserving local surgical treatment and on the transcutaneously measured oxygen pressure (tcPO2) in patients with ischaemic lesions was investigated in a prospective, open, controlled, randomized study. All of the 30 patients recruited to the study suffered from a peripheral arterial occlusive disease Fontaine stage IV with progressive symptoms and arterial occlusions below the knee. 15 patients received iloprost intravenously for 6 hours per day in an individual tolerable dose (mean dose: 1.7 ng/kg/min). 15 patients in the control group received no trial therapy. During the treatment period each patient underwent minor amputation or skin grafting. Wound healing after surgery and tcPO2 were assessed. The long-term efficacy of iloprost was assessed by following the patients for one year. The iloprost treatment was in general well tolerated and all patients completed the study in accordance with the trial protocol. Primary postoperative wound healing as the responder-criterion was observed in 9 patients (60%) of the iloprost group and in 4 patients (27%) of the control group. Patients with iloprost therapy were especially likely to show wound healing if they received the operation approximately in the mid of the treatment phase. The effect of therapy lasted for one year after the end of the treatment in 7 of 9 classified responders of the iloprost group. After one year the responder rate of 47% in the iloprost group was still 20% higher than in the control group. Surgical revisions were necessary in 7 patients (47%) of each group. 2 patients (13%) treated with iloprost and 4 control patients (27%) underwent major amputation. The mortality was 13% = 2 of 15 patients (iloprost) and 7% = 1 of 15 patients (control). Transcutaneous PO2-measurements were very reproducible over a long-term period under standardized conditions. A significant effect of iloprost on the tcPO2 was shown. There was a mean increase of 8.1 mmHg +/- 11.2 (mean +/- SD) in the foot of the affected limb after an average 6-week therapy (p < 0.05). At the same time a significant difference in the tcPO2-changes between responders and nonresponders was demonstrated (p < 0.05). Patients with primary wound healing had a greater increase in tcPO2 than patients whose wounds did not heal. An increase of at least 10 mmHg (6 patients) in tcPO2 during the infusion after 3 weeks of therapy predicted primary

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Arterial Occlusive Diseases; Blood Gas Monitoring, Transcutaneous; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Middle Aged; Prospective Studies

GISAP, a multicentre open study, was aimed to confirm the feasibility and safety of iloprost treatment in normal clinical practice and to identify subgroups of patients with severe POAD more likely to benefit from iloprost treatment than others. One hundred forty six patients were treated at the maximum tolerated dose of iloprost up to 2 ng/kg/min, 6 hours infusion per day, for a minimum of 3 weeks and a maximum of 8 weeks. Clinical efficacy was assessed by rest pain reduction, analgesic consumption, healing of trophic lesions, walking ability. A significant improvement of the efficacy parameters was recorded during and at the end of treatment: no difference between diabetics and non diabetics, stage III and IV patients was observed. After one year follow-up 10% major amputation and 6.8% death were recorded, these events were balanced between the diabetic and non diabetic patients. Overall 80% of the patients at risk of amputation at entry to the trial were alive with a viable limb after one year. Tolerability resulted quite acceptable. Even with the limitation of an open trial, it has been confirmed the therapeutic potential of iloprost in the treatment of POAD patients.

Topics: Adult; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Diabetes Complications; Female; Humans; Iloprost; Male; Middle Aged; Treatment Outcome

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

Iloprost, a stable carbaprostacyclin analog, was infused (up to 2-4 ng/kg/min) for 12 h daily on 5 consecutive days into the forearm vein of 13 patients with peripheral arterial occlusive disease (PAOD) of legs (stages IIb-III). All vasodilatory and antiplatelet drugs were stopped three weeks earlier. For comparison, dextran was infused in a randomized, crossover, double-blind manner with an average interval of 3 months. Iloprost increased significantly ankle systolic pressure and ankle/arm pressure ratio for the follow-up period of one month. Foot skin temperature increased insignificantly. Pain-free walking distance was prolonged up to 1.51 times by iloprost and 1.14 times by dextran (p less than 0.05). Venous occlusion plethysmography showed no improvement in the blood flow of legs. Eight patients experienced a subjective improvement in their clinical status with iloprost. Ten patients suffered from mild to severe headache, nausea, transient rest pain of legs, and hypotension. One patient with gastric ulcer history was withdrawn because of mild hematemesis, not definitely drug-related. No significant changes occurred in standard laboratory safety control or in hemostasis. The results suggest that a 5-day iloprost infusion exerts a mild favourable effect on patients with PAOD.

Topics: Aged; Ankle; Arterial Occlusive Diseases; Blood Pressure; Cardiovascular Agents; Dextrans; Double-Blind Method; Epoprostenol; Female; Humans; Iloprost; Infusions, Intravenous; Leg; Male; Middle Aged; Random Allocation; Time Factors

The effectiveness of iloprost, a prostacyclin derivative, was assessed in a placebo-controlled multicentre trial on 101 patients with chronic arterial disease, stage IV. All patients were on a basic local treatment, 53 randomly being assigned to the iloprost group, 48 to the placebo one. Both groups received identical saline infusions, one with the other without iloprost. Infusions were given on 28 consecutive days, iloprost being added at a dose of up to 2 ng/kg.min over six hours. At the end of the treatment period, 32 of 52 patients (61.5%) of the iloprost group and eight of the 47 in the placebo group (17%) had partial or complete healing of ulcers (P less than 0.05), the treatment effect persisting in both groups for a mean duration of at least one year. Iloprost was well tolerated, once individual dosages had been appropriately adjusted. Facial flushes, headache and nausea were the most common side effects. Heart rate and blood-pressure variations did not differ between the two groups.

Topics: Adult; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Cardiovascular Agents; Chronic Disease; Clinical Trials as Topic; Epoprostenol; Female; Follow-Up Studies; Humans; Iloprost; Male; Middle Aged; Multicenter Studies as Topic; Placebos; Random Allocation; Time Factors

Topics: Arterial Occlusive Diseases; Cardiovascular Agents; Clinical Trials as Topic; Diabetic Angiopathies; Epoprostenol; Humans; Iloprost; Multicenter Studies as Topic; Random Allocation

Topics: Adult; Aged; Arterial Occlusive Diseases; Blood Flow Velocity; Blood Viscosity; Clinical Trials as Topic; Diabetic Angiopathies; Double-Blind Method; Epoprostenol; Female; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Random Allocation

In a randomized patient-blind study iloprost or hydroxy-ethyl starch 200/0.5 were given i.v. 5 h daily for 2 weeks to 24 patients suffering from severe intermittent claudication due to peripheral vascular disease. An increase in pain-free walking distance of more than 50% occurred in 6 of 11 patients after the iloprost infusions and in 7 of 12 patients after HES treatment. No significant effects on haemodynamic or clinical chemistry tests were observed.

Topics: Aged; Anti-Arrhythmia Agents; Arterial Occlusive Diseases; Blood Viscosity; Epoprostenol; Erythrocyte Aggregation; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Male; Middle Aged; Physical Exertion; Plethysmography

The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II-III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg X min for 4 h, with an interval of 2-3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5-2.0 ng/kg X min iloprost, indicating that iloprost reduced platelet stimulation by 50%-70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg X min. It is concluded that iloprost administered i.v. at doses of 1-2 ng/kg X min in patients with stage II-III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.

Topics: Adult; Aged; Arterial Occlusive Diseases; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Evaluation; Epoprostenol; Female; Hemodynamics; Humans; Iloprost; Male; Middle Aged; Platelet Aggregation; Random Allocation; Time Factors

We describe a case of acute ischemia of the 2nd, 3rd and 4th fingers of the right hand secondary to peripheral vascular occlusive disease induced by repeated intra-arterial cocaine injections. The complete occlusion of the distal arteries resolved following treatment with iloprost, a synthetic stable analogue of prostacyclin PGI2, in addition to anticoagulants and antibiotics.

Topics: Acute Disease; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anticoagulants; Arterial Occlusive Diseases; Cocaine-Related Disorders; Drug Therapy, Combination; Hand; Humans; Iloprost; Ischemia; Male; Nadroparin; Peripheral Vascular Diseases; Treatment Outcome; Vasodilator Agents

In its more severe form heparin induced thrombocytopenia (HIT) is a rare immune mediated complication of heparin administration that potentially has catastrophic results, and significant mortality. In view of the severity of this condition it is important for the clinician to maintain a high index of suspicion and get alerted to the HIT syndrome by the precocity of platelet count decrease in any patient group, and especially in those previously exposed to heparin. We report on a 72-year-old woman who developed HIT syndrome that was complicated by recurrent arterial thromboses after receiving postoperative antithrombotic prophylaxis with tinzaparin, a low molecular weight heparin. The patient was successfully treated with iloprost (Ilomedin, iloprost tromethamine, Schering) a stable prostacyclin analogue, at the acute phase of the syndrome, followed by long-term treatment with clopidogrel (Plavix, clopidogrel bisulfate, Sanofi) an inhibitor of adenosine diphosphate (ADP) receptor. Although direct thrombin inhibitors have been proven to be effective for the treatment of HIT thrombosis, they do not completely eliminate the morbidity and mortality of this disorder. Our case report suggests that antithrombotic treatment by targeting of the activated platelets with a potent platelet inhibitor during the acute phase of type II HIT syndrome followed by long-term administration of oral anticoagulation may be an additional, safe and effective therapeutic alternative that merits to be systematically studied.

Topics: Aged; Arterial Occlusive Diseases; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Iliac Artery; Iloprost; Leg; Platelet Aggregation Inhibitors; Popliteal Artery; Radiography; Recurrence; Syndrome; Thrombocytopenia; Thrombosis; Ticlopidine; Tinzaparin

Topics: Adult; Arterial Occlusive Diseases; Humans; Iloprost; Magnetic Resonance Imaging; Male; Platelet Aggregation Inhibitors; Syndrome; Ulnar Artery; Ultrasonography, Doppler, Duplex

Peripheral vascular occlusive disease (PAOD) is frequently seen in patients suffering from coronary heart or cerebrovascular disease and is, considered as a prognostic predictor for the morbidity and mortality of this patient group. Thus, secondary antithrombotic and antiplatelet prophylaxis in these patients is not limited to achievement of long-term patency of the revascularized or recanalized arterial segment, but plays as well a pivotal role for the prevention of myocardial infarction and stroke. Generally, claudicants as well as patients undergoing percutaneous transluminal angioplasty (PTA), supragenicular femoro-popliteal artificial bypass surgery, aortofemoral, iliaco-femoral unilateral bypass, or aortobifemoral Y-graft implantation with unimpaired arterial outflow are treated life-long with low dose acetylsalicylic acid (ASA) 75-250 mg. On the other hand, those undergoing axillo-femoral, femoro-femoral crossover, aorto-profundal or femoro-popliteal infragenicular and femoro-distal venous bypass surgery should be treated with vitamin K antagonists. The role of Clopidogrel in secondary prevention after peripheral revascularization and recanalization still needs to be defined.

Topics: Administration, Oral; Angioplasty, Balloon; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Confidence Intervals; Dipyridamole; Drug Therapy, Combination; Embolectomy; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Iloprost; Intermittent Claudication; Leg; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thrombectomy; Ticlopidine; Time Factors; Vitamin K

Topics: Alprostadil; Arterial Occlusive Diseases; Controlled Clinical Trials as Topic; Extremities; Fibrinolytic Agents; Humans; Iloprost; Intermittent Claudication; Ischemia; Meta-Analysis as Topic; Microcirculation; Multivariate Analysis; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Prognosis; Retrospective Studies; Vasodilator Agents; Walking

Treatment of arteriopathy of the lower limbs (ALL) with vasoactive drugs must follow French health laws recently introduced in regard to the prescription of unuseful drugs and treatments and the frequency at which some patients resort to specific drugs and treatments. Prescription of vasoactive drugs in ALL requires the existence of functional discomfort. Prescription of only one vasoactive drug is sufficient.. Results of published clinical trials demonstrate the efficacy of vasoactive drugs for the relief of claudication related to arteriopathy. To conform to the rules of the European Drug Agency, treatment with vasoactive drugs which improve the walking distance is recommended as "symptomatic treatment of arterial claudication in ALL". Iloprost is only used in the treatment of permanent ischemia. Prescription of vasoactive drugs is part of a scheme of therapeutic indications that are well known and rigorous. Rules of hygiene and reduction of risk factors are the essential preliminary elements. In the case of arterial claudication due to femoral or distal obliteration, chemical medication is suggested, whereas in the case of iliac lesion, angioplasty should be considered.. Walking is recommended in all the cases; however, usually less than a quarter of all patients will conform to this recommendation. Vasoactive drugs thus find their place in the therapeutic scheme. Evaluation of the efficiency of vasoactive drugs rises above simple measures of the walking distance, rather integrating quality of life and usefulness of the treatment.

Topics: Angioplasty; Arterial Occlusive Diseases; Contraindications; Drug Prescriptions; Drug Utilization; Femoral Artery; France; Humans; Iliac Artery; Iloprost; Intermittent Claudication; Ischemia; Leg; Legislation, Drug; Quality of Life; Vasodilator Agents; Walking

To help in determining management strategy as an alternative to amputation by using a synthetic prostacycline, a preliminary study was undertaken in 12 patients (11 men and one woman), with a mean age of 71.08 years, ie, 13 limbs evaluated at the stage of amputation. All patients were treated with a combination of iloprost and physical therapy (massage, specific exercises, cardiorespiratory training). Static transcutaneous oxygen pressure (TcPO2) was measured, with a sensitization test by verticalization and inhalation of oxygen, on day (D) D0, D15, D28, D60, D180, and D365. Results were analyzed in absolute terms and by tissue oxygenation ratio (TOR) (ratio between absolute values of TcPO2 in the foot and those of a reference chest electrode). Supine TOR and vertical TOR, with values of 36.67 and 65.08, respectively, appeared to be significantly linked to the variable "preservation of limb". At 1 year, seven limbs were preserved (53.85%) while amputation had been scheduled for all the patients treated. Evidence was found in all patients who kept their limb of stability (7.69%) and a decrease in (30.77%) or disappearance of pain (15.38%) at 1 year.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Analysis of Variance; Arterial Occlusive Diseases; Blood Gas Monitoring, Transcutaneous; Combined Modality Therapy; Female; Humans; Iloprost; Leg; Logistic Models; Male; Middle Aged; Physical Therapy Modalities; Prognosis; Vasodilator Agents

Topics: Arterial Occlusive Diseases; Hemodynamics; Humans; Iloprost; Intermittent Claudication; Vasodilator Agents

A 34-year-old woman was hospitalized for severe acute arterial insufficiency of the limbs. Overuse of ergotamine derivative was acknowledged by the patient, who had a long history of migraine headaches. An arteriogram showed diffuse arterial spasm and occlusion of right leg distal arteries. Intravenous infusion of a stable prostacyclin analog (Iloprost) was administered. Rapid and complete improvement of arteriospasm was noted within a few hours, confirmed by a further arteriogram. This appears to be one of the rare case reports of successful limb salvage by use of Iloprost for ergotism.

Topics: Adult; Angiography; Arterial Occlusive Diseases; Ergotamine; Ergotism; Female; Humans; Iloprost; Leg; Migraine Disorders; Vasoconstrictor Agents; Vasodilator Agents

The authors, after examination of pharmacologic profile of Iloprost, prostacyclin synthetic analogue, report their clinical experience from January 1992 to June 1997 on 105 patients with severe ischaemia of inferior limbs. They utilize two protocols: 0.5-2 ng/kg/min x 6 hs once a day x 28 days and 1-1.5 ng/kg/min x 6 hs twice a day x 12 days. The first protocol were practise along the first 2 years; the second on following period as long as today. The results, evaluated on clinical criteria, are referred entity and time of pain remission and decrease of analgesic use, performance status improvement, increase of gear autonomy and, if present, wound healing. The incidence of amputation was 4.76% (5 pts). The authors issue that Iloprost is a conservative treatment, often alternative with amputation, giving sometimes to patients a longtime functional "restitutio ad integrum".

Topics: Arterial Occlusive Diseases; Critical Illness; Diabetic Angiopathies; Follow-Up Studies; Humans; Iloprost; Infusion Pumps; Ischemia; Leg; Treatment Outcome; Vasodilator Agents

The authors analyse the short-term and medium-term effects of iloprost prostanoid derivate on hemostatic status in a group of patients with obliterating vascular disease of the lower limbs. The study included 10 patients (6 males, 4 females; aged 52 + 5 years old) suffering from Fontaine's stage 3 obstructive arterial disease. After a 10-hour fast each patient received a 6-hour iv infusion of iloprost at a dose of 2 ng/kg/min (approx 50 gamma) a venous blood sample was collected before and after infusion. The test was repeated using the same method after 4 weeks of treatment with the same dose of the drug. The following parameters were analysed in serum: fibrinogen (F) (IL coagulometric method), Factor VII (F VII) (IL coagulometric method), antithrombin II (AT III) (IL chromogenic method), protein C (PC) II coagulometric method) and protein S (PS) (IL coagulometric method). After the first infusion a significant increase was observed in AT III (p > 0.05), whereas other indices showed no significant variations. After treatment for 4 weeks AT III was again enhanced after infusion (p > 0.05); with regard to the basal values of other parameters, a significant reduction (p > 0.05) was found in F VII, whereas no other significant changes were observed. In the light of these results the authors suggest an antithrombotic effect of the drug documented by the short-term increase in AT III probably due to lower consumption, and a medium-term reduction in F VII due to trophic effect of the drug at a vasculoparietal level resulting in the depression of FVII tissue activation factors.

Topics: Arterial Occlusive Diseases; Blood Coagulation Factors; Female; Humans; Iloprost; Male; Middle Aged; Platelet Aggregation Inhibitors

On 10 patients, suffering from peripheral arterial disease, with critical limb ischaemia, the CO2 production during ischaemia has been evaluated at 1st and at 28th day of treatment with iloprost. The study demonstrated that the drug is able to improve the tissue resistance to ischaemia, with a significant (p < 0.05) reduction of the CO2 production. The authors underline that this study is one of the first confirmations, in vivo and on the man, of the previous experimental findings, made in isolated arterial tissue.

Topics: Arterial Occlusive Diseases; Carbon Dioxide; Humans; Iloprost; Ischemia; Oxygen

Transcutaneous oxygen pressure (tcPo2), laser Doppler flux and capillary microscopy have been used to examine the forefoot skin in 5 healthy men and 8 patients with severe peripheral arterial occlusive disease in order to evaluate the dose dependent effects of iloprost on skin microcirculation. Iloprost was infused IV starting at 0.0625 ng.kg-1.min-1 and doubling the dose every 15 min up to 2 ng.kg-1.min-1. While tcPo2 at an electrode core temperature of 44 degrees C decreased in both patients and controls, there was a significant dose dependent increase in tcPo2 (37 degrees C) in the controls from 0.25 ng.kg-1.min-1. In the patients the reaction was variable: it was decreased in two and increased in 6, with a maximum either at 0.25-0.5 ng.kg-1.min-1 (n = 3) or at the highest dose (1.0 or 2.0 ng.kg-1.min-1; n = 3). Mean laser Doppler flux in both groups was increased, although the reaction was not consistent in the patients. Density of forefoot skin capillaries was reduced in 3 patients, and in the others the flow velocity was very low. During infusion of iloprost, both an increase in capillary density and blood cell velocity were observed. The effects were of variable intensity and occurred at varying doses, some appeared early and diminished as the dose was increased, and others were found only at 2 ng.kg-1.min-1. Adverse effects were numerous, extending from harmless skin flushing to mental changes and a quickly reversible attack of angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Arterial Occlusive Diseases; Blood Gas Monitoring, Transcutaneous; Dose-Response Relationship, Drug; Female; Hot Temperature; Humans; Iloprost; Infusions, Intravenous; Lasers; Male; Microcirculation; Middle Aged; Reference Values; Skin

The aim was to determine the effects of the stable prostacyclin analogue iloprost (ZK 36374) on systemic haemodynamics and on cardiovascular neural control.. The buffering effect was examined of intravenous and intracoronary iloprost infusion on the excitatory sympathetic reflexes elicited from the heart by (1) intracoronary injections of bradykinin and (2) transient coronary artery occlusion.. 22 conscious mongrel dogs of either sex, weight 20-25 kg, were used.. ECG, systemic arterial pressure, left atrial pressure, and left ventricular pressure, and contractility (dP/dt) were continuously monitored for the duration of the experiments. Iloprost infusion reduced left ventricular pressure, mean arterial pressure, and dP/dt without causing significant changes in heart rate. Transient non-hypertensive coronary artery occlusion increased heart rate and depressed contractility. During intravenous iloprost infusion, coronary artery occlusion no longer elicited an increase in heart rate, while left ventricular dP/dt was more drastically reduced. This pattern of response was not substantially modified by beta adrenergic blockade, whereas the blockade of muscarinic receptors with atropine was accompanied by hypotension and a greater reduction of dP/dt. The observation of a reduced pressor response to the intracoronary injections of bradykinin during iloprost administration further indicated a restraining effect of iloprost on the sympathetic reflexes elicited from the heart.. The data suggest the hypothesis that the protective effects on the ischaemic myocardium observed with iloprost infusions may arise not only from its vasodilator and antiplatelet properties, but also from its capacity to blunt excitatory sympathetic reflexes.

Topics: Animals; Arterial Occlusive Diseases; Blood Pressure; Bradykinin; Coronary Disease; Dogs; Heart; Heart Rate; Hemodynamics; Iloprost; Sympathetic Nervous System; Vagus Nerve; Ventricular Function, Left

The pharmacokinetics of iloprost were studied in 12 hospitalized patients suffering from severe peripheral arterial occlusive disease (PAOD) stages III or IV according to Fontaine. The patients were 8 males and 4 females aged from 49 to 83 years. Apart from PAOD, several other concomitant diseases were present, e.g. myocardial and/or renal insufficiency, diabetes and hypertension. Patients were treated daily with i.v. infusions of iloprost at dosages of 1.0-3.3 ng/kg/min over a period of 4 to 6 h. Dose-normalized steady-state plasma levels ranged from 39 to 100 pg/ml (65 +/- 20 pg/ml). The total clearance accounted for 16 +/- 5 ml/min/kg. Post-infusion disposition in the plasma was biphasic with half-lives of 4 +/- 2 min and 37 +/- 8 min. The plasma level profiles obtained on days 4 and 14 of treatment in 3 patients were similar. Sex specific kinetic differences were not observed. In comparison to healthy volunteers, studied in an earlier trial, total clearance was slightly lower and consequently steady state levels were increased (p less than 0.05) in PAOD patients. Half-lives in the plasma were not significantly different.

Topics: Aged; Aged, 80 and over; Arterial Occlusive Diseases; Female; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Time Factors

Topics: Arterial Occlusive Diseases; Chronic Disease; Gangrene; Humans; Iloprost; Infusions, Intra-Arterial; Leg; Male; Middle Aged

Topics: Adenosine Diphosphate; Arterial Occlusive Diseases; Blood Platelets; Cardiovascular Agents; Collagen; Epoprostenol; Fingers; Humans; Iloprost; Ischemia; Male; Middle Aged; Platelet Aggregation; Scleroderma, Systemic; Time Factors

The hemodynamic and antithrombotic action of ZK 36374, a stable carbacyclin derivative of prostacyclin, was studied during electrically-induced coronary artery thrombosis in the open chest anesthetized pig. Infusion of ZK 36374 (100 ng/kg/min, n = 6) had no effect on heart rate and cardiac output, but caused a 20% reduction in mean arterial blood pressure by peripheral vasodilation. In animals receiving solvent or no drug prior to thrombosis induction, the time to occlusive coronary artery thrombosis (TOT) was 30 +/- 2 minutes (mean +/- SEM, n = 17). Pretreatment with an i.v. infusion of ZK 36374 (100 ng/kg/min) prolonged TOT by 50% to 47 +/- 7 minutes (p less than 0.005, n = 6). This prolongation of TOT was not due to the lower blood pressure in the ZK 36374 group, as dihydralazine in a dose that lowered arterial blood pressure to the same extent had no effect on TOT (32 +/- 4 minutes, n = 4). The results indicate that ZK 36374 may be useful in delaying (or preventing) occlusive coronary artery thrombi.

Topics: Animals; Arterial Occlusive Diseases; Cardiotonic Agents; Coronary Disease; Disease Models, Animal; Epoprostenol; Fibrinolytic Agents; Hemodynamics; Iloprost; Platelet Aggregation; Swine