iloprost and Ischemia

For many years, the only pharmacological option for patients with critical limb ischemia (CLI) unsuitable for revascularization has been prostanoids; however, some recent guidelines have become very restrictive regarding their use. We review the available evidence on the use of prostanoids and analyze the guideline positions as well as the possible reasons for changes over time. In most placebo-controlled trials and meta-analyses, prostanoids showed a significant effect in improving rest pain, promoting ulcer healing and reducing major amputations. Results for iloprost were especially consistent. Different prostanoid drugs have different evidence of efficacy, thus using a generic term "prostanoids" is misleading. Unfortunately, the available evidence is often of low quality and probably not sufficient to support an extensive use of prostanoids in all patients, and further high-quality randomized trials are needed. Consequently, some recent guidelines do not recommend treatment with prostanoids in this setting. However, in our opinion, pending definitive evidence, patients with CLI who have a viable limb in whom revascularization is unfeasible or has a poor chance of success, without alternative to amputation, may benefit from treatment with iloprost, balancing harms and benefits in each case.

Topics: Alprostadil; Amputation, Surgical; Humans; Iloprost; Ischemia; Pain; Prostaglandins; Treatment Outcome; Vasodilator Agents

Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010.. To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention.. For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials.. Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention.. Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author.. For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life.. We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.

Topics: Alprostadil; Amputation, Surgical; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Nafronyl; Nicotinic Acids; Pentoxifylline; Peripheral Vascular Diseases; Prostaglandins; Randomized Controlled Trials as Topic; Vasodilator Agents

Peripheral arterial disease (PAD) is a common circulatory problem that can lead to reduced blood flow to the limbs, which may result in critical limb ischaemia (CLI), a painful manifestation that occurs when a person is at rest. The mainstay of treatment for CLI is surgical or endovascular repair. However, when these means of treatment are not suitable, due to anatomical reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and prostanoids have both been shown to reduce pain from CLI in people who suffer from non-reconstructable PAD, but there is currently insufficient evidence to determine if one treatment is superior. Due to the severity of the rest pain caused by CLI, and its impact on quality of life, it is important that people are receiving the best pain relief treatment available, therefore interest in this area of research is high.. To compare the efficacy of lumbar sympathectomy with prostanoid infusion in improving symptoms and function and avoiding amputation in people with critical limb ischaemia (CLI) due to non-reconstructable peripheral arterial disease (PAD).. The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 29 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched clinical trials databases for ongoing or unpublished studies.. Randomised controlled trials (RCTs), with parallel treatment groups, that compared lumbar sympathectomy (surgical or chemical) with prostanoids (any type and dosage) in people with CLI due to non-reconstructable PAD.. Three review authors independently selected trials, extracted data and assessed risk of bias. Any disagreements were resolved by discussion. We performed fixed-effect model meta-analyses, when there was no overt sign of heterogeneity, with risk ratios (RRs) and 95% confidence intervals (CIs). We graded the quality of evidence according to GRADE.. We included a single study in this review comparing lumbar sympathectomy with prostanoids for the treatment of CLI in people with non-reconstructable PAD. The single study included 200 participants with Buerger's disease, a form of PAD, 100 in each treatment group, but only 162 were actually included in the analyses. The study compared an open surgical technique for lumbar sympathectomy with the prostanoid, iloprost, and followed participants for 24 weeks.Risk of bias was low for most evaluated domains. Due to the nature of the treatment, blinding of the participants and those providing the treatment would be impossible as a surgical procedure was compared with intravenous injections. It was not mentioned if blinded assessors evaluated the study outcomes, therefore, we judged subjective outcomes (i.e. pain reduction) to be at unclear risk of detection bias and objective outcomes (i.e. ulcer healing, amputation and mortality) at low risk of detection bias. We also rated the risk of attrition bias as unclear; 38 out of 200 (19%) participants were not included in the analysis without clear explanation (16 of 100 in the iloprost arm and 22 of 100 in the sympathectomy arm). The quality of evidence was low due to serious imprecision because the study numbers were low and there was only one study included.The single included study reported on the outcome of complete healing without pain or major amputation, which fell under three separate outcomes for our review: relief of rest pain, complete ulcer healing and avoidance of major amputation. We chose to keep the outcome as a singularly reported outcome in order to not introduce bias into the outcomes, which may have been the case if reported separately. The limited evidence suggests participants who received prostaglandins had improved complete ulcer healing without rest pain or major amputation when compared with those who received lumbar sympathectomy (RR 1.63, 95% CI 1.30 to 2.05), but as it was the only included study, we rated the data as low-quality and could not draw any overall conclusions. The study authors stated that more participants who received prostaglandins reported adverse effects, such as headache, flushing, nausea and abdominal discomfort, but only one participant experienced severe enough adverse effects to drop out. Five participants who underwent lumbar sympathectomy reported minor wound infection (low-quality evidence). There was no reported mortality in either of the treatment groups (low-. Low-quality evidence from a single study in a select group of participants (people with Buerger's disease) suggests that prostaglandins are superior to open surgical lumbar sympathectomy for complete ulcer healing without rest pain or major amputation, but possibly incur more adverse effects. Further studies are needed to better understand if prostaglandins truly are more efficacious than open surgical lumbar sympathectomy and if there are any concerns with adverse effects. It would be of great importance for future studies to include other forms of PAD (as Buerger's disease is a select type of PAD), other methods of sympathectomy as well as data on quality of life, complications and cost-effectiveness.

Topics: Humans; Iloprost; Ischemia; Leg Ulcer; Pain Management; Peripheral Arterial Disease; Prostaglandins; Sympathectomy; Thromboangiitis Obliterans; Vasodilator Agents

Raynaud's Syndrome is a frequent manifestation of digital ischemia which occurs or is aggravated upon exposure to cold temperatures or emotional distress. Primary Raynaud is a benign disease which predominantly affects younger women and is transient without serious sequelae. In contrast, secondary Raynaud is usually one of the manifestations of systemic disease and is, in addition to symptoms of the basic disease, associated with ischemic lesions. The diagnosis of primary Raynaud is mostly based on the clinical presentation. In secondary Raynaud, additional investigating techniques including imaging investigations and laboratory tests for the detection of underline disease are needed. Treatment is based on lifestyle modification, which includes smoking cessation, avoiding low outside temperatures, avoiding the use of vibrating tools and limiting repeated hand actions. Drug treatment consists of calcium-channel blockers, nitroglycerine ointments, prostacyclins and various new drugs such as endothelin receptor antagonists, phosphodiesterase inhibitors and serotonin receptor antagonists. Most of these drugs are effective in less than 50% of treated patients and do not completely abolish vasospastic attacks, but reduce the severity and frequency of attacks. The prostacyclin derivate iloprost is the most promising drug in the management of secondary Raynaud's disease. Other therapeutic procedures including chemical or surgical sympathectomy are obsolete and without any long-term positive effects.

Topics: Calcium Channel Blockers; Epoprostenol; Humans; Iloprost; Ischemia; Life Style; Neglected Diseases; Nitroglycerin; Raynaud Disease; Smoking Cessation; Vasodilator Agents

Topics: Antihypertensive Agents; Bosentan; Endothelin Receptor Antagonists; Female; Fingers; Humans; Iloprost; Ischemia; Male; Raynaud Disease; Risk Factors; Scleroderma, Systemic; Skin Ulcer; Sulfonamides; Vasodilator Agents

Prostanoids (alprostadil and iloprost) are used for the treatment of patients with critical limb ischemia in whom revascularization procedure is inadequate or proved to be unsuccessful. According to a Cochrane analysis (CD006544) prostanoids differ in their effects on rest-pain relief and ulcer healing.. To study the efficacy and safety of prostanoids for critical limb ischemia.. Systematic literature search and meta-analysis (mixed treatment comparison) was performed.. Seven randomized controlled trials including 964 patients were analyzed. Compared to placebo, both alprostadil (OR: 3.2 95% CI: 1.7-5.5 and OR: 1.8 95% CI: 0.6-4.3) and iloprost (OR: 2.7 95% CI: 1.7-4.2 and OR: 2.5 95% CI: 1.0-5.4) were more efficacious with regard to rest-pain relief and ulcer healing and the difference between the two prostanoids was not significant (OR: 1.2 95% CI: 0.7-1.9 and OR: 0.74 95% CI: 0.3-1.5). Adverse events occurred significantly more often with both drugs compared to placebo, however, they were less frequent with alprostadil than with iloprost (OR 0.2 95% CI: 0.1-0.3).. Prostanoids have favorable effect on rest-pain relief and ulcer healing in critical limb ischemia, without statistically significant difference between the two available drugs. The Cochrane study (CD006544) reported mistaken results due to defaults in the analysis.

Topics: Alprostadil; Humans; Iloprost; Ischemia; Leg; Pain; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rest; Skin Ulcer; Vasodilator Agents

Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular diseases in the general population. While numerous treatments have been adopted for different disease stages, there is no option other than amputation for patients presenting with critical limb ischaemia (CLI), unsuitable for rescue or reconstructive intervention.. To determine the effectiveness and safety of prostanoids in patients presenting with CLI.. The Cochrane Peripheral Vascular Diseases Group searched their trials register (last searched October 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue 4) for publications describing randomised controlled trials (RCTs) of prostanoids for CLI. We ran additional searches in MEDLINE, EMBASE, LILACS, and SciSearch, and we also contacted pharmaceutical companies and experts, in order to identify unpublished data and trials still underway.. Randomised controlled trials describing efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments, in patients presenting with CLI, without chance of rescue or reconstructive intervention.. Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author.. We retrieved 532 citations which after the first screening resulted in 111 potential studies. Finally, after exclusion of studies of poor quality and a lack of sufficient information, 20 trials were included in the review.Prostanoids seem to have efficacy regarding rest-pain relief (risk ratio (RR) 1.32, 95% confidence interval (CI) 1.10 to 1.57; P = 0.003), and ulcer healing (RR 1.54, 95% CI 1.22 to 1.96). Iloprost also shows favourable results regarding major amputations (RR 0.69, 95% CI 0.52 to 0.93). The more frequently reported adverse events when using prostanoids were headache, facial flushing, nausea, vomiting and diarrhoea.. Despite some positive results regarding rest-pain relief, ulcer healing and amputations, there is no conclusive evidence based on this meta-analysis of the long-term effectiveness and safety of different prostanoids in patients with CLI. Further well-conducted, high quality randomised double-blinded trials should be performed.

Topics: Alprostadil; Amputation, Surgical; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Peripheral Vascular Diseases; Prostaglandins; Randomized Controlled Trials as Topic; Vasodilator Agents

The article deals with the analysis of the treatment outcomes obtained in management of patients suffering from lower-limb critical ischaemia treated with iloprost, a stable analogue of the prostacyclin. The results of six randomized placebo-controlled trials and eleven trials of other drugs are described in this article. The meta-analysis of the iloprost studies confirmed the efficacy of the drug in decreasing the size of ulcers, pain relief, extremity amputation rate. Whereas the other examined drugs have not demonstrated such properties with rare exception.

Topics: Humans; Iloprost; Ischemia; Leg; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome

Ischaemic ulcerations of the fingertips are common in SSc and a source of pain and disability. Healing has been demonstrated with intravenous iloprost and two studies with bosentan have demonstrated reduction in the occurrence of new digital ulcers (DUs) over 4-6 months of treatment. Both bosentan studies showed no benefit in healing DU and because of this, net DU burden is no different between drug and placebo and accordingly secondary measures of outcome including pain and hand functionality are inconsistently affected. While it is likely an artefact, it remains unclear that current outcome measures including the Scleroderma Health Assessment Questionnaire (SHAQ), the UK Functional Score and the Michigan Hand Questionnaire are sensitive to change in the domain of digital ischaemia. Major events including amputation and hospitalization occur too infrequently to serve as practical measures of outcome in trials. Future studies of DU therapies will benefit from development of an ulcer-specific measure of outcome.

Topics: Bosentan; Fingers; Hand Dermatoses; Humans; Iloprost; Ischemia; Scleroderma, Systemic; Severity of Illness Index; Skin Ulcer; Sulfonamides; Treatment Outcome; Vasodilator Agents

Revascularization by either bypass surgery or endovascular recanalization is considered the first-choice treatment in patients with critical limb ischemia (CLI). Only conservative options are left in CLI patients in whom successful revascularization strategies are not possible: in these patients, at present, prostanoids (iloprost and prostaglandin [PGE1]) represent the pharmacological treatment of choice. Iloprost resulted more effective than PGE1, in a 6 month follow-up, in both limb savage and in prevention of cardiovascolar death, either in diabetic or non diabetic patients with unreconstructable CLI. In our experience, in patients who have responded to a first cycle of therapy (early responders), performed for at least 2-3 weeks, cyclic annual further treatments with iloprost are usually able to stabilize arterial disease, with a regression to Fontaine II stage and, in absence of further arterial complications, with complete limb preservation for an unlimited period of time. In non-responder patients, who are not urgently supposed to undergo amputation, a second cycle of iloprost carried out within few months from the first one, is able to increase the percentage of responders to prostanoids (late responders). Vice versa, in non-responders to repeat prostanoid cycles, it is useful to verify the outcomes of further attempts at saving, the symptomatic limb by surgical or endovascular re-timing, spinal cord stimulation, gene or stem cell therapy. Our recent better outcomes are related to earlier microvascular diagnosis and to earlier, repeat, pharmacological treatments with iloprost. Transcutaneous oxygen and carbon dioxide monitoring improves the possibility of an earlier diagnosis of microvascular damages and categorizes CLI patients in responders and non-responders after prostanoid treatments.

Topics: Adolescent; Adult; Aged; Algorithms; Alprostadil; Amputation, Surgical; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Iloprost; Ischemia; Leg; Limb Salvage; Male; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Vasodilator Agents

Most patients with systemic sclerosis (SSc) have Raynaud's phenomenon (RP), which is often more severe than idiopathic RP. This study was a meta-analysis to determine the efficacy of calcium-channel blockers for the treatment of RP in SSc. The primary outcome measures were frequency and severity of ischemic attacks, digital skin temperature, patient and physician global assessments, and digital ulcers.. The Cochrane search strategy was used to ascertain all trials in all languages. Primary data sources included Medline, Current Contents, and the Cochrane Controlled Trials Register. Studies that met the inclusion criteria were randomized controlled trials of >2 days' duration with a dropout rate of <35%. Twenty-nine studies were found, of which 8 randomized controlled trials were eligible for inclusion. The total number of patients included was small (n = 109). Most trials included primary and secondary RP, and the main reasons for trial exclusion were inability to extract subset data on SSc patients (18 trials), data published previously (2 trials), and lack of a control group (1 trial). Data were abstracted independently by 2 reviewers, and either a weighted mean difference (WMD) or a standardized mean difference (SMD) was calculated for all continuous outcomes; however, information was not available for all outcomes within trials.. The WMD of all calcium-channel blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5 trials) for the reduction in the frequency of ischemic attacks over a 2-week period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95% CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and -0.99 (95% CI -1.74, -0.24), respectively.. Calcium-channel blockers for RP in SSc have been tested in several small clinical trials and appear to lead to significant clinical improvement in both the frequency and the severity of ischemic attacks. Most trials were crossover trials in which order effect was not studied. This could have introduced bias. The results of this study suggest that the efficacy of calcium-channel blockers in reducing the severity and frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large, randomized controlled trial needs to be conducted.

Topics: Calcium Channel Blockers; Cross-Over Studies; Humans; Iloprost; Injections, Intravenous; Ischemia; Losartan; Randomized Controlled Trials as Topic; Raynaud Disease; Scleroderma, Systemic; Skin Temperature; Skin Ulcer

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

A review was conducted of published clinical trials of adjuvant medical therapy in infrainguinal bypass procedures to evaluate the strength of the evidence for the use of various agents.. Trials were identified by literature search. The methods used were reviewed and the results with each agent tested were assessed taking into account the soundness of the study design.. Thirty-three studies were identified; fewer than half had a randomized and double-blind design. Most were single-centre studies including a mixture of different surgical procedures and patients with varying degrees of lower limb ischaemia. Clinical outcomes were seldom reported. The median sample size was 61. The median follow-up duration was 12 months, but was often not standardized for all patients in a trial. Only aspirin in prosthetic grafts and ticlopidine in vein grafts have been shown in well designed, double-blind, randomized, controlled trials to reduce the likelihood of occlusion in infrainguinal bypass grafts.. The majority of the trials reviewed had significant deficiencies in their design, reducing the reliance that can be placed on their results. Further studies are required to investigate adequately the effectiveness of existing medical therapies for the maintenance of infrainguinal bypass grafts.

Topics: Alprostadil; Anticoagulants; Aspirin; Chemotherapy, Adjuvant; Clinical Trials as Topic; Dextrans; Double-Blind Method; Femoral Artery; Heparin, Low-Molecular-Weight; Humans; Iloprost; Ischemia; Leg; Platelet Aggregation Inhibitors; Popliteal Artery; Prospective Studies; Randomized Controlled Trials as Topic; Ticlopidine; Vascular Surgical Procedures

Topics: Anti-Infective Agents, Local; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Platelet Aggregation Inhibitors; Tibial Arteries; Vasodilator Agents

Iloprost is a synthetic stable analogue of prostacyclin (PGI2), which shares its antiaggregating and vasodilating properties. Iloprost has been administered by i.v. route to patients with critical limb ischaemia (CLI) of different origin (maximal dosage: 2 ng/kg/min 6 hours/day infusion for 14-28 days). In patients with claudicatio intermittens (Fontaine stage II) iloprost improved the time to claudication and the maximal walking distance on treadmill, with an effect still lasting 60 days after suspension. This benefit was not related to a significant improvement in blood flow. Five multicentric, perspective, randomized versus placebo studies in patients with more severe CLI (Fontaine stage III-IV) susceptible to surgical treatment, showed that iloprost was able to reduce pain and ulcer dimensions. Furthermore, tha amputation rate of the ischemic limb was significantly lower in patients treated with iloprost during a 6 month follow-up (p < 0.01). Iloprost was also more effective than aspirin in causing pain relief and ulcer healing in patients with thromboangiitis obliterans and more effective than nifedipine in reducing frequency, intensity and duration of ischemic episodes in patients with Raynaud's phenomenon. Minor side effects of iloprost administration are represented by facial flushing, tachycardia, headache, nausea, vomiting, abdominal cramping, diarrhoea, whose frequency ranges from 16% to 70%; major collateral effects, occurring in less than 5% of patients, are above all represented by severe hypotension and angina pectoris. Clinical data indicate therefore that iloprost treatment can allow to improve the clinical conditions and the prognosis in patients with critical ischemia of the limbs, not candidate to surgical revascularization, by causing a relief of pain, a reduction in ulcer dimensions and deferring amputation.

Topics: Clinical Trials as Topic; Critical Illness; Humans; Iloprost; Ischemia; Leg

Use of prostanoids in vascular surgery is valuable in various conditions: intra and postoperatively, during limb salvage procedures, they are useful to lower peripheral resistances, and in patients with limited gangrene, when surgery is not feasible, they improve limb blood flow. After some years of subjective clinical evaluation, multicentric randomized clinical trials started; the aim was to quantify the real benefit derived from the use of prostanoids to the evolution of limb ischemia and to the improvement of results of surgical revascularization. We have not yet definitive results; preliminary data show a better immediate patency rate of femoro-distal bypass grafts and a critical reduction in long term limb amputations.

Topics: Clinical Trials as Topic; Critical Illness; Humans; Iloprost; Intraoperative Care; Ischemia; Leg; Salvage Therapy

Topics: Animals; Arachidonic Acid; Cyclooxygenase Inhibitors; Drug Synergism; Epoprostenol; Fibrinolytic Agents; Graft Survival; Humans; Iloprost; Ischemia; Lipoxygenase; Lipoxygenase Inhibitors; Nitric Oxide; Postoperative Complications; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Skin; Skin Transplantation; Surgical Flaps; Thrombosis; Vasodilator Agents

Aim This pilot study aimed to reveal whether combination of electrostimulation with iloprost treatment achieves better results compared to iloprost alone in patients with critical limb ischemia. Material and methods Patients were randomized into Group 1 ( n = 11, mean age: 65.3 ± 4.2 years, received iloprost infusion protocol alone) or Group 2 ( n = 11, mean age: 62.9 ± 6.7, received iloprost infusion plus standardized protocol of peroneal nerve electrostimulation). Electrostimulation was delivered with 1 Hz frequency, 27 mA current, and 200 ms pulse width. Peak blood flow velocities in the anterior and posterior tibialis arteries were measured with duplex ultrasound. Results There was a slight insignificant increase in blood velocity in anterior tibialis artery in Group 1 (from 17.6 ± 13.0 to 18.6 ± 13.1, p = 0.57), whereas the increase in Group 2 was marked (from 23.8 ± 18.3 to 32.2 ± 19.7, p = 0.01). Blood velocity in posterior tibialis artery also increased in both groups, but it was not of statistical significance. No significant difference was found between two groups in regard to final pulse oximetry oxygen saturation levels. Conclusion Electrostimulation of the peroneal nerve caused a substantial increase in anterior tibialis artery blood velocity when used as an adjunct to medical therapy in patients with critical limb ischemia.

Topics: Aged; Blood Flow Velocity; Combined Modality Therapy; Electric Stimulation Therapy; Female; Humans; Iloprost; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Peroneal Nerve; Pilot Projects; Prospective Studies; Regional Blood Flow; Tibial Arteries; Time Factors; Treatment Outcome; Turkey; Ultrasonography, Doppler, Duplex; Vascular Patency; Vasodilator Agents

Intravenous iloprost is an important option in the treatment of ischemic disease of the lower limbs; however, the administration of therapy is frequently compromised because of the need for long cycles of infusion in a hospital setting. The aim of the study is to evaluate the efficacy, safety, feasibility, and the economic impact of infusion therapy in the outpatient setting.. Twenty-four consecutive patients were treated with iloprost at their homes where they were administered a slow rate of infusion for 24 hours a day, during 9.9 ± 2.3 days, with a portable syringe pump (Infonde®).. The clinical condition of patients evaluated with the modified SVS/ISCVS scale significantly improved after treatment (+1.29 ± 1.04 points vs. baseline, p<0.001). The drug was well tolerated; neither significant adverse events associated with medication nor problems related to venous access were recorded at home. Ninety-six percent of patients successfully completed the entire treatment cycle, and the evaluation questionnaire showed a high acceptance of the therapy. From the perspective of the hospital authority, lower direct medical costs were estimated for the domiciliary infusion process compared with the inpatient infusion setting.. Treatment with iloprost in the outpatient setting is effective, safe, feasible, and more acceptable to patients than infusion at the hospital. In addition, it has a favorable economic and organizational impact on the medical ward.

Topics: Administration, Intravenous; Adult; Aged; Humans; Iloprost; Infusion Pumps; Infusions, Intravenous; Ischemia; Lower Extremity; Middle Aged; Vasodilator Agents

Platelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB₂ and 8-iso-PGF(₂α) excretion rate, as in vivo indexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB₂ [499 (277-807) vs. 380 (189-560) pg/mg creatinine, p < 0.0001] and 8-iso-PGF(₂α) [533 (316-842) vs. 334 (196-540) pg/mg creatinine, p < 0.0001] as well as plasma sCD40L [1540 (1005-3015) vs. 948 (845-2030) pg/ml, p < 0.0001]. Furthermore, a significant increase in plasma nitrate plus nitrite levels has been observed [26.8 (18.8-35.9) vs. 43.7 (33.0-75.5) μM, p < 0.0001]. A significant direct correlation was also found between urinary 8-iso-PGF(₂α) and 11-dehydro-TXB2 before and after iloprost treatment (Rho = 0.695, p < 0.0001). In conclusion, we report that a short-term course of iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.

Topics: Aged; Aged, 80 and over; Aspirin; Biomarkers; Blood Platelets; CD40 Ligand; Chi-Square Distribution; Critical Illness; Dinoprost; Drug Administration Schedule; Female; Humans; Iloprost; Inflammation Mediators; Infusions, Intravenous; Ischemia; Italy; Lipid Peroxidation; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Platelet Activation; Platelet Aggregation Inhibitors; Thromboxane B2; Time Factors; Treatment Outcome

The incidence of severe limb ischemia (SLI) is high among haemodialysis (HD) patients. Limb rescue rate after surgical revascularization is relatively poor compared with patients with normal renal function. Prostanoids are an interesting category as adjuvants to revascularization. New vessel growth develops not exclusively by proliferation of endothelial cells in vascular extremities but also by cells mobilized from the bone marrow (HSC), transformed into endothelial progenitor cells (EPC) contributing to both re-endothelialization and neovascularization. Basal number of HSC and EPC is significantly reduced in HD patients and correlated with a subsequent defective neovascularization. The aim of this study was to evaluate the effects of perioperative treatment with iloprost in uremic patients with acute ischemia of lower limbs, undergoing surgical revascularization, on endothelial progenitor cells, hypothesizing a possible biological mechanism induced by the prostanoids. A search was also made for vascular remodeling processes through the analysis of the concentrations of soluble adhesion molecules (i-CAM, v-CAM, e-selectin), biochemical markers of endothelial activation. Thirty HD patients with SLI undergoing peripheral revascularization were enrolled (15 were treated with iloprost and 15 with a placebo). Iloprost was administered as an intra-arterial bolus of 3000 ng over 1 to 3 min immediately after revascularization and in the same affected artery. Serum samples were taken before revascularization (T0), at 6 (T6) and 24 h (T24) after infusion to measure sICAM-1, sE-selectin, and sVCAM-1, and for quantification of HSC and EPC. Progenitors were identified by specific surface markers CD34+, CD133+ and VEGFR2+. Count was conducted using PROCOUNT performed in a TRUCOUNT tube and with a FACSort flow cytometer. Before revascularization, all patients showed a decreased number of HSC and EPC. After 6 h, HSC augmented significantly compared with T0 in both groups. The iloprost group attained a significant increase compared with the placebo group. HSC levels reduced drastically at T24. EPC augmented significantly compared with basal level after 24 h. In the iloprost group, the increase was considerable compared with the placebo group. A close negative correlation, assessed by Pearson coefficient (r), was found between HSC and EPC at T24 in the iloprost group (R = 0.82 P < 0.01). Adhesion molecules had increased levels at T6 and T24 in both groups. Moreover, a clo

Topics: Aged; Cell Adhesion Molecules; Cell Count; Combined Modality Therapy; Endothelial Cells; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Neovascularization, Physiologic; Renal Dialysis; Uremia; Vasodilator Agents

Patients with critical limb ischemia (CLI) have low levels of endothelial progenitor cells (EPC). Iloprost has been demonstrated to stimulate vascular endothelial growth factor (VEGF) and promote angiogenesis. We investigated the effects of iloprost on EPC levels in vivo in CLI patients. Twenty-three patients with stage III and IV CLI were treated with iloprost for four weeks, improving clinical and instrumental parameters. Mononuclear cells isolated from peripheral blood were cultured to obtain "early" EPC, evaluated counting adherent cells with double positivity for acetylated low-density lipoprotein uptake and Ulex Europaeus lectin at flow cytometry. These cells also co-expressed the monocyte markers CD14 and CD45. Iloprost increased EPC number in the whole patient population: pre-treatment median: 13,812/ml; range: 1,263-83,648/ml; post-treatment median: 23,739/ml; range: 3,385-99,251/ml; p = 0.035, irrespective of age, sex, disease stage or atherosclerosis risk factors. In conclusion, iloprost increases EPC number in peripheral blood in vivo. Such an effect may have therapeutic relevance.

Topics: Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Carbon Dioxide; Cells, Cultured; Critical Illness; Endothelial Cells; Extremities; Female; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Ischemia; Male; Oxygen; Stem Cells; Treatment Outcome; Vascular Endothelial Growth Factor A

To evaluate the use and advantage of microsurgical intervention and intravenous iloprost administration in delayed infantile artery injuries.. Four patients were followed up and treated in our clinic between June 2003 and June 2006 for infantile artery injuries and distal ischemia. The average age of the 4 infants (3 girls, 1 boy) was 134.7+/-33.6 days. The reason for all of the artery injuries was iatrogenic. Tissue necrosis started in patches in 2 babies who were admitted at the 12(th) hour after ischemia (19(th) and 22(nd) hours), and therefore the artery was repaired by microsurgery. Iloprost infusion was also used in addition to the conservative treatments. The other 2 patients were assessed before the first 12 h after distal ischemia and were treated by iloprost without any surgical intervention. None of the patients lost any tissue or extremities during the 9 months (average) follow-up time. One of our patients died following the ventricular septal defect repair at the 9(th) month after a successful repair of artery.. We believe that intravenous iloprost infusion is very effective in the treatment of distal ischemia when used in addition to the conservative treatment methods for artery injuries in infants.

Topics: Arteries; Combined Modality Therapy; Female; Humans; Iatrogenic Disease; Iloprost; Infant; Infusions, Intravenous; Ischemia; Male; Microsurgery; Peripheral Vascular Diseases; Vasodilator Agents

To evaluate the effects of iloprost, in addition to surgery, on the outcome of acute lower limb ischemia (ALLI).. Post-hoc analysis of a randomized, double-blind, placebo-controlled study.. In the context of the ILAILL (ILoprost in Acute Ischemia of Lower Limbs) study, 192 elderly patients (>70 years old) undergoing surgery for ALLI were assigned to receive perioperative iloprost (intra-arterial, intra-operative bolus of 3000 ng, plus intravenous infusion of 0.5-2.0 ng/kg/min for six hours/day for 4-7 days following surgery), or placebo (iloprost: n=100; placebo: n=92). Patients were followed-up for three-months following surgical revascularization.. The combined incidence of death and amputation (primary study end-point) was significantly reduced in patients treated with iloprost (16.0% vs 27.2% in the placebo group; hazard ratio 1.99, 95% confidence interval 1.05-3.75, p=0.03). A statistically significant lower mortality (6.0%) was reported in patients receiving iloprost, compared to controls (15.2%) (hazard ratio 2.93, 1.11-7.71, p=0.03). The overall incidence of death and major cardiovascular events was lower in patients receiving iloprost compared to those assigned placebo (24.0% and 35.9%, respectively), at the limits of statistical significance (relative risk 1.64, 0.97-2.79, p=0.06).. These results confirm the poor outcome in elderly patients with ALLI. Based on a subgroup analysis iloprost, as an adjuvant to surgery, appears to reduce the combined end-point of death and amputation.

Topics: Acute Disease; Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Agents; Chemotherapy, Adjuvant; Double-Blind Method; Extremities; Female; Humans; Iloprost; Incidence; Ischemia; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Eicosanoids with vasodilating and angiogenic properties have been postulated to be effective therapies for critical leg ischemia (CLI) secondary to atherosclerotic peripheral arterial disease. The ability to deliver active drug to the site of action at adequate doses for sufficient duration has been a major limitation in the clinical development of such therapies. Lipo-ecraprost is a lipid-encapsulated prostaglandin E1 prodrug with the potential to deliver active prostaglandin to the site of critical arterial ischemia. The current trial was designed to test the hypothesis that lipo-ecraprost would improve amputation-free survival in patients with CLI who had no revascularization options.. The study was randomized, multicenter, double blind, and placebo controlled. Patients who met clinical and hemodynamic criteria were randomized to receive placebo or lipo-ecraprost (60 microg) administered intravenously on each of 5 days per week, for a total of 8 weeks. The study's primary endpoint was the rate of a composite end point of death or amputation above the level of the ankle at 180 days (6 months).. The study was terminated on a recommendation from the Data and Safety Monitoring Board after the completion of a protocol-specified interim analysis for futility. At the time of termination, 383 of the planned 560 patients had been randomized, of which 379 received at least one dose of study medication and thus were included in the intention-to-treat population. Twenty-three patients were lost to follow-up and were not available for 6-month assessments. At 6 months of follow-up, there were 23 amputations in the 177 patients who received placebo, and 29 amputations in the 179 patients randomized to lipo-ecraprost. At 6 months, 10 deaths had occurred in the placebo group and 18 deaths had occurred in the lipo-ecraprost arm. Changes in lower-extremity hemodynamics over the 6-month study period did not differ between the placebo and lipo-ecraprost treatment arms.. Intensive treatment with lipo-ecraprost failed to modify the 6-month amputation rate in patients with CLI who were not candidates for revascularization.

Topics: Adult; Aged; Aged, 80 and over; Alprostadil; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Carriers; Female; Follow-Up Studies; Humans; Iloprost; Infusions, Intravenous; Intermittent Claudication; Ischemia; Leg; Limb Salvage; Lipids; Male; Middle Aged; Pain Measurement; Peripheral Vascular Diseases; Reference Values; Risk Assessment; Treatment Outcome; Ultrasonography

High rate of complications has been reported following revascularization for acute limb ischemia (ALI). No adjuvant pharmacologic treatment, apart from anticoagulation and standard perioperative care, has been shown clinically effective.. Aim of this study was to evaluate the effects of the prostacyclin analog iloprost as adjuvant to surgery for ALI.. A total of 300 patients were randomly assigned to receive perioperative iloprost (intra-arterial, intraoperative bolus of 3000 ng, plus intravenous infusion of 0.5-2.0 ng/kg/min for 6 hours/day for 4-7 days following surgery), or placebo. The primary endpoint was the combined incidence of death and amputation at 3-month follow-up. Secondary endpoints were the incidence of each single major complication, total event rate, symptomatology, and tolerability.. The combined incidence of death and amputation was 19.9% in the placebo and 14.1% in the iloprost group (relative risk, 1.56; 95% confidence interval, 0.89-2.75, P = 0.12, Cox regression analysis). A statistically significant lower mortality (4.7%) was reported in patients receiving iloprost, compared with controls (10.6%; relative risk, 2.61; 95% confidence interval, 1.07-6.37, P = 0.03). The overall incidence of fatal plus major cardiovascular events was 33.1% and 22.8% in placebo and iloprost groups, respectively (relative risk, 1.61; 95% confidence interval, 1.04-2.49, P = 0.03). No serious adverse reactions occurred after iloprost administration, nor differences in the incidence of bleeding or hypotension between treatment groups.. Although at lower levels than previously reported, our results confirm the severity of ALI. Iloprost as adjuvant to surgery significantly reduced mortality and overall major event rate. Further data are needed to support this finding, and to face a still open medical issue.

Topics: Aged; Amputation, Surgical; Anticoagulants; Cause of Death; Chemotherapy, Adjuvant; Double-Blind Method; Female; Follow-Up Studies; Heparin; Humans; Hypotension; Iloprost; Infusions, Intravenous; Injections, Intra-Arterial; Ischemia; Lower Extremity; Male; Placebos; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Risk Factors; Treatment Outcome; Vasodilator Agents

Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Apoptosis; Cells, Cultured; Female; Gene Expression Regulation; Humans; Iloprost; Interleukin-6; Ischemia; Lower Extremity; Male; Monocytes; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; RNA, Messenger; Treatment Outcome; Tumor Necrosis Factor-alpha

To evaluate the long term efficacy of treatment with intravenous iloprost for severe Raynaud's phenomenon (RP) and ischemic leg ulcers in patients with autoimmune systemic diseases.. Prospective observational study over 2 years with iloprost (intravenous infusions, 0.5 to 2 ng/kg/min, initial cycle of 5 consecutive days and maintenance infusions during 24 h monthly, lengthened when it was needed) in patients with severe RP and ischemic leg ulcers whithout response to conventional therapy. Treatment was halted in patients with a good response after one year of treatment, with regular clinical controls.. We treated 23 patients. Iloprost reduced significantly the mean number (SD) of monthly episodes of RP (150.38 [102.04] initially and 40.05 [78.06] at the end; p < 0.0005), the mean highest duration of episodes of RP (21.86 [26.96] min initially and 7.14 [9.87] min at the end; p = 0.013), the associated pain (p = 0.005), and the mean number of ischemic digital (4.25 [2.86] initially and 0.63 [2.25] at the end; p = 0.003) and leg ulcers (1.67 [0.52] initially and 0.33 [0.52] at the end; p = 0.01). Articular symptoms and inflammatory markers did not improve. Treatment was stopped in 8 patients (in 5 for a very good evolution and in 3 for other causes), and only 1 of them needed to be treated again. Side effects were seen in all cases but always disappeared after slowing infusion.. Iloprost was effective in the long term treatment of severe RP and ischemic leg ulcers in patients with autoimmune systemic diseases.

Topics: Adult; Autoimmune Diseases; Female; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Male; Prospective Studies; Raynaud Disease; Severity of Illness Index; Time Factors; Vasodilator Agents

In a randomized cross-over study, the effect of PGE(1) and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE(1) and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE(1): first hour 20 microg, next 2h 30 microg each. Iloprost: first hour 0.5 ng/kg/min, next 2h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tcPO(2)) values increased much more with PGE(1). Median tcPO(2) increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE(1) and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE(1)) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE(1).

Topics: Aged; Aged, 80 and over; Alprostadil; Cross-Over Studies; Drug Tolerance; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Microcirculation; Vasodilator Agents

Two separate studies are described using the same prostacyclin analogue in a similar group of patients.. to assess the tolerability and efficacy of two dose regimens of oral Iloprost compared with placebo in the treatment of patients with ischaemic ulcers, gangrene or rest pain due to severe arterial disease over a period of 4 weeks (Study A) and one year (Study B).. multicentre, placebo controlled, double-blind, randomized prospective studies.. 178 (study A) and 624 (study B) patients with trophic skin lesions (ulcers or gangrene) or ischaemic rest pain due to severe arterial disease. To confirm severe arterial disease patients were required to have a systolic ankle Doppler pressure of 70 mmHg or less or a toe systolic Doppler pressure of 50 mmHg or less in one leg. In both studies patients were randomly allocated to three treatment groups: placebo, low dose Iloprost (50-100 microgram twice a day) or high dose (150-200 microgram twice a day) In Study A the main outcome measures were tolerability of different doses of Iloprost and death, major amputation, healing of trophic lesions and relief of rest pain at the end of the follow up, which was 5 months after the end of the treatment. In Study B the primary end point was time to major amputation and stroke or death up to 12 months. Secondary pre-defined end points included the combined end point of patients alive without amputation, no trophic skin changes, no rest pain and not on regular analgesics.. the proportion of patients who completed the 4-week treatment period in Study A at the intended dose was 58%, 43%, 45% respectively in the placebo, low dose and high dose Iloprost groups. In an intention to treat analysis the proportion of patients who survived without major amputation, ulcers or gangrene and had no rest pain was 11% in the placebo group, 19% in the low dose iloprost group and 28% in the high dose Iloprost group. The pooled Iloprost groups showed a statistically significantly better result than the placebo group (p=0.04), as did the high dose Iloprost group compared to the placebo (p=0.014). In Study B there was no treatment benefit in terms of a primary end point of amputation and death. However the secondary combined end point of patients who survived without a major amputation, ulcers or gangrene and had no rest pain, nor a need for regular analgesia was favourable for Iloprost, with 18% of patients in the placebo group reaching this optimal secondary end point, compared to 23% in the low dose Iloprost group and 26% in the higher dose Iloprost group (p<0.05).. oral Iloprost administered for a year showed no clear benefit in patients with advanced severe leg ischaemia (PAOD III and IV). The results obtained with 4 weeks' treatment in Study A and in previous trials of intravenous Iloprost could not be reproduced

Topics: Administration, Oral; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Peripheral Vascular Diseases; Prospective Studies; Reference Values; Severity of Illness Index; Treatment Outcome; 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

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

The aim of this study was to investigate the haemostatic effects of iloprost, a stable analogue of prostacyclin, in patients with peripheral arterial disease. In a group of 13 patients with obliterative arteriopathies of the lower limbs the plasma levels of thrombomodulin (TM), betathromboglobulin (beta-TG), D-dimer (DD) and plasminogen activator-inhibitor (pAI-1) were measured, and compared to the values obtained from 10 healthy volunteers. All the parameters were found to be significantly higher in vasculopathic patients. These haemostatic evaluations were carried out after 4 weeks of treatment with iloprost up to 2 ng/kg/min, 6 hours infusion per day. During and at the end of treatment a clinical improvement was recorded. The patients also showed a significant decrease in plasma beta-TG and DD at the end of treatment. These data suggest that iloprost exerts clinical improvement, in who may have a part the decrease of platelet activation and of fibrin turnover.

Topics: Adult; Female; Hemostatics; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.

Topics: Adult; Aged; Endothelins; Female; Fingers; Gangrene; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Middle Aged; Raynaud Disease; Scleroderma, Systemic; Ulcer; Vasodilator Agents

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

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

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

In 51 hospitals in six European countries 713 patients requiring below-knee amputation for ischaemic disease were studied prospectively. The patients were allocated randomly to receive standard postoperative treatment or standard treatment plus intravenous infusion of the prostacyclin analogue iloprost for 6 h per day over 14-21 days. Healing of the amputation stump and the need for reamputation at a higher level were similar in the two groups. Overall at 3 months 59 per cent of stumps had healed, 19 per cent of patients had required reamputation at a higher level, 11 per cent had died and the remaining 11 per cent remained with unhealed stumps. Preoperative characteristics were analysed as possible risk factors or markers for primary healing, reamputation and death. Previous arterial reopening procedures (surgical or radiological) almost doubled the chances of primary stump healing (P < 0.05). The surgeon's assessment of the likelihood of healing was wrong in 21 per cent of cases in which the operating surgeon thought that healing would probably occur and in 52 per cent of those in which it was thought healing was improbable.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Middle Aged; Prognosis; Prospective Studies; Reoperation; Risk Factors; Wound Healing

A prospective randomized placebo-controlled trial was conducted to determine the effects of the stable prostacyclin analogue iloprost on early graft patency and hemodynamic parameters during femorodistal reconstruction for critical leg ischemia. Peripheral resistance and graft blood flow were measured using an operative Doppler flowmeter and graft pressure transducer. Postoperative graft surveillance was continued at 1-month and then at 3-month intervals by duplex Doppler ultrasonography, measurement of ankle-brachial pressure indices, and intravenous digital subtraction angiography when indicated. In patients receiving 3000 ng of iloprost (n = 45) infused into the graft on completion there was an immediate mean decrease in peripheral resistance of 44% that persisted to skin closure in comparison with controls (n = 38) in whom no such decrease in resistance occurred (p < 0.001, Wilcoxon test). During the same period, mean graft blood flow increased in iloprost-treated patients by 74.5% compared with controls in whom there was a 6% increase in flow (p < 0.001). Primary cumulative patencies at 1 month were significantly higher in iloprost-treated grafts, 98% compared to 83% for controls (p < 0.05, log-rank test). Cumulative primary patencies at 1 year and secondary patencies at 1 month and 1 year were also greater in the iloprost-treated group (67%, 98%, and 87.6%, respectively) compared to controls (65%, 86%, and 79.3%, respectively), but these did not achieve statistical significance. A single bolus infusion of iloprost has prolonged beneficial effects on graft blood flow and peripheral resistance during femorodistal reconstruction. This is reflected by improved early primary graft patencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Blood Flow Velocity; Female; Femoral Artery; Graft Occlusion, Vascular; Humans; Iloprost; Intraoperative Period; Ischemia; Leg; Male; Middle Aged; Prospective Studies; Saphenous Vein; Vascular Patency; Vascular Resistance

We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis.. Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks.. Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion.. Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.

Topics: Adult; Aged; Double-Blind Method; Female; Fingers; Hemodynamics; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Middle Aged; Platelet Activation; Raynaud Disease; Scleroderma, Systemic; Skin; Temperature; Ulcer

A randomised placebo-controlled trial was conducted to investigate the effect of iloprost, a stable prostacyclin mimetic, on peripheral resistance during femoro-distal bypass. Patients undergoing femoro-distal long saphenous vein bypass for critical ischaemia received 3000 ng of iloprost or placebo infused into the graft via an unligated side branch over 2 min. Graft blood flow and peripheral resistance were measured for 20 min, using an operative Doppler flowmeter (OpDop 130, SciMed, U.K.) and a pressure transducer to record graft pressure. Postoperatively, graft blood flow was assessed by daily duplex ultrasound for 7 days. Iloprost produced an immediate drop in peripheral resistance in all cases (n = 18) by a mean (range) of 40% (4-80%) compared with controls (n = 15) in whom there was a 5.3% (-8 to +36%) increase in resistance (p less than 0.01, Wilcoxon test). Decreased peripheral resistance in iloprost-treated patients persisted to 20 min. The largest decreases in peripheral resistance occurred in patients with the highest initial resistances (r = 0.56, p less than 0.02). Graft flow during the same period increased by 52% (-7 to 294%) compared with controls in whom there was a 6% (-17 to 26%) increase in flow, (p less than 0.01). Flow remained elevated by 53% over baseline values at 1 week post-infusion in the iloprost-treated group but this did not achieve statistical significance compared to controls in whom flow also increased by 13%. Iloprost produces an immediate decrease in peripheral resistance associated with a prolonged increase in graft blood flow. This may reduce graft failure in the early postoperative period.

Topics: Aged; Anastomosis, Surgical; Drug Administration Schedule; Female; Femoral Artery; Humans; Iloprost; Intraoperative Period; Ischemia; Leg; Male; Middle Aged; Vascular Resistance

A randomised placebo-controlled trial was conducted to investigate the effects of iloprost, a stable prostacyclin analogue, on peripheral resistance, graft blood flow and mean systemic arterial blood pressure (MABP) during femoro-crural arterial bypass. 3000ng of iloprost, infused into the graft, produced an immediate drop in peripheral resistance by a mean (range) of 40% (4-80%) (P less than 0.01, Wilcoxon). Decreased peripheral resistance persisted to 20 minutes. Graft flow during the same period increased by 52% (-7 to 294%) (P less than 0.01). A transient maximal drop in mean MABP of 22% from 83-65 mmHg occurred 5 minutes post iloprost infusion but caused no detrimental effects and recovered to baseline values by 10 mins. Iloprost produces an immediate decrease in peripheral resistance associated with a prolonged increase in graft blood flow. This may reduce graft failure in the early postoperative period.

Topics: Aged; Aged, 80 and over; Female; Hemodynamics; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Regional Blood Flow; Transplantation, Autologous; Vascular Resistance

The effects of i.v. iloprost given for 14-28 days on six month outcome in patients with severe inoperable lower limb ischaemia were investigated in a double-blind placebo controlled study. More iloprost patients (64%) survived with a viable limb than placebo patients (42%). Iloprost improved prognosis in all subgroups of patients, but patients with lower presenting ankle Doppler pressures had a worse outcome than patients with higher pressures.

Topics: Aged; Aged, 80 and over; Aging; Blood Pressure; Double-Blind Method; Female; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Regional Blood Flow

A randomised placebo-controlled trial was conducted to investigate the effects of iloprost, a stable prostacyclin analogue, on peripheral resistance, during femoro-crural arterial bypass. 3000 ng of iloprost, infused into the graft, produced an immediate drop in peripheral resistance by a mean (range) of 43% (4-80%; p less than 0.01, Wilcoxon). Decreased peripheral resistance persisted to 20 minutes. Graft flow during the same period increased by 59.8% (-7 to 294%; p less than 0.01) and this increase persisted after the operation. Iloprost produces an immediate decrease in peripheral resistance associated with a prolonged increase in graft blood flow. This may reduce graft failure in the early postoperative period.

Topics: Aged; Aged, 80 and over; Blood Flow Velocity; Combined Modality Therapy; Female; Foot; Graft Occlusion, Vascular; Humans; Iloprost; Ischemia; Male; Middle Aged; Saphenous Vein; Vascular Resistance

A number of patients (151) with ischaemia of the lower limb presenting as ulcers or gangrene and/or rest pain were entered into a multicentre randomised double-blind controlled study of intravenous iloprost or placebo given for 14-28 days. Patients were assessed for evidence of ulcer healing as judged by reduction in size with granulation at the base and relief of rest pain sufficient for discharge from hospital. Based on these criteria, 45% in the iloprost and 29% in the placebo group showed evidence of improvement of clinical status at the end of treatment (p less than 0.05). At 6 months follow-up improvement was maintained in 42% of iloprost patients and 26% of placebo patients (p less than 0.01). At this follow up 64% of the iloprost patients and 42% of the placebo patients were alive with a viable limb. Thirty-one per cent of the iloprost patients and 47% of the placebo patients underwent major amputation (p less than 0.05). It has been shown that iloprost significantly improves patients with ischaemic ulcers or gangrene compared with placebo. This improvement is maintained for up to 6 months after treatment resulting in a reduced major amputation rate.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Double-Blind Method; Female; Follow-Up Studies; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Middle Aged

152 patients with thromboangiitis obliterans (Buerger's disease) and pain from critical leg ischaemia were randomly allocated to receive iloprost, a chemically stable prostacyclin analogue, or low-dose aspirin, for 28 days in a double-blind trial. On review, 19 patients did not fulfil the stringent entry criteria. Of the other 133 patients, 98 also had leg ulcers. After 21-28 days, 58 (85%) of 68 iloprost-treated patients showed ulcer healing or relief of ischaemic pain, compared with 11 (17%) of 65 in the aspirin-treated group. 43 (63%) on iloprost treatment had complete relief of pain, compared with 18 (28%) on aspirin. Ulcers healed completely in 18 of 52 (35%) who received iloprost compared with 6 of 46 (13%) who received aspirin. 6 months after the start of treatment, the response rate was 45 of 51 (88%) patients treated with iloprost compared with 12 of 44 (21%) patients treated with aspirin.

Topics: Adolescent; Adult; Amputation, Surgical; Anti-Arrhythmia Agents; Arm; Aspirin; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Epoprostenol; Follow-Up Studies; Humans; Iloprost; Ischemia; Leg; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Thromboangiitis Obliterans

The efficacy of iloprost, a stable prostacyclin analog, was investigated in a placebo-controlled trial in 109 diabetics with ischemic lesions. 56 patients were randomly allocated to iloprost and 53 patients to placebo. Iloprost was intravenously applied for 6 hours daily on 28 consecutive days at an individually tolerated dose up to 2 ng/kg/min. The control group received identical solvent volumes. In addition all patients had an intensive basic, mainly local, therapy. At the end of the treatment in the iloprost group 31 of 50 patients (62%) showed partial (greater than 30%) or total healing of the lesion(s). In the placebo group this was the case in 12 of 51 patients (22.5%). The difference of 38.5% was statistically significant (p less than 0.05, chi 2-test, alpha = 0.05, beta = 0.1). The percentage of patients who were free of pain increased from 23% to 42% (+19%) in the iloprost group and from 38% to 48% (+10%) in the placebo group. After dose-titration iloprost was well tolerated. Flush, headache and abdominal complaints were the most frequent side effects. Heart rate and blood pressure were not influenced and the control of diabetes was not altered.

Topics: Adult; Aged; Diabetic Angiopathies; Female; Foot; Humans; Iloprost; Ischemia; Male; Middle Aged

The clinical efficacy of the prostacyclin analogue iloprost was studied during a 2 week treatment and 6 month follow-up period in 103 patients with ischaemic ulcers who were randomised to receive active treatment or placebo. Responders were defined as those patients who achieved healing of at least one third of the ulcer area during the study period. The overall responder rate was 41.3%, compared with 25% for the control group (P = 0.086). Side effects including flushing and headache, were common. The study population had a mortality of 23% during the 6 month period, the amputation rate was 43.5% for iloprost and 50% for placebo treated patients. In this severely diseased population of patients a treatment period limited to 2 weeks did not sufficiently improve ulcer healing.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Female; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Male; Middle Aged

Topics: Anesthesia, Local; Anesthetics, Local; Epinephrine; Humans; Iloprost; Ischemia

Topics: Angiography, Digital Subtraction; Foot; Humans; Iloprost; Ischemia; Lower Extremity; Perfusion; Treatment Outcome

Inflammation is a component in the pathogenesis of critical limb ischemia. We aimed to assess how inflammation affects response to treatment in patients treated for critical limb ischemia using neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocytes ratios (PLR) as markers of inflammation.. Patients in a single tertiary cardiovascular center with critical limb ischemia unsuitable for surgical or interventional revascularization were retrospectively identified. Data were collected on medical history for risk factors, previous surgical or endovascular revascularization, and outcome. A standard regimen of low molecular weight heparin, aspirin, statins, iloprost infusions, and a standard pain medication protocol were applied to each patient per hospital protocol. Patients with improvement in ischemic pain and healed ulcers made up the responders group and cases with no worsening pain or ulcer size or progression to minor or major amputations made up the non-responders group. Responders and Non-responders were compared for risk factors including pretreatment NLR and PLR.. 268 included patients who were not candidates for surgical or endovascular revascularization were identified. Responders had significantly lower pretreatment NLR (4.48 vs 8.47, p < 0.001) and PLR (162.19 vs 225.43, p = 0.001) values. After controlling for associated risk factors NLR ≥ 4.63 (p < 0.001) and PLR ≥ 151.24 (p = 0.016) were independently associated with no response to treatment.. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocytes ratio are markers of inflammation that are reduced in patients improving with medical treatment suggesting a decreased state of inflammation before treatment in responding patients.

Topics: Aged; Cardiovascular Agents; Critical Illness; Female; Humans; Iloprost; Ischemia; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Peripheral Arterial Disease; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Wound Healing

We investigated the protective effect of iloprost against ischemia/reperfusion (I/R) injury in rat ovary. We used 32 female Sprague-Dawley rats randomly allocated to four experimental groups: sham, ischemia, I/R and I/R + iloprost. Ovarian torsion was established in all rats except the sham group. The torsion group was exposed to ischemia for 3 h. The detorsion group was exposed to 3 h ischemia applied + 3 h reperfusion. The detorsion + iloprost group was exposed to ischemia for 3 h + reperfusion for 3 h + intravenous (IV) iloprost infusion for 60 min starting at the beginning of reperfusion. Ovaries were removed and prepared for histopathological evaluation. Reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the blood. The total histopathological injury score and MDA level of the ischemia group were significantly higher than for the sham group. Ovarian injury score and MDA level following I/R increased compared to the ischemia group. Iloprost administration reduced the total injury score and MDA level. The GSH level was higher in the I/R + iloprost group than in the I/R group. We concluded that IV iloprost administration reduces I/R injury in rat ovarian tissue.

Topics: Animals; Antioxidants; Female; Glutathione; Iloprost; Ischemia; Malondialdehyde; Ovary; Oxidative Stress; Rats, Sprague-Dawley; Reperfusion Injury

Topics: Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Skin; Ulcer

Topics: Administration, Intravenous; Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Drug Administration Schedule; Female; Humans; Iloprost; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Access Devices; Wound Healing

The aim of this study is to evaluate the role of Iloprost as an early predictor of successful revascularization in patients affected by ischemic diabetic foot ulcers (DFUs).. Consecutive patients with ischemic DFUs with persistent low TcPO2 (<30mmHg) one day after a technical successful Percutaneous Transluminal Angioplasty (PTA) have been included. All patients underwent Iloprost infusion and TcPO2 has been recorded at days 3, 14 and 30. According to the TcPO2 reported at day 3, patients were divided into two groups: group A (patients with TcPO2 ≥30mmHg) and group B (patients with TcPO2 <30mmHg). Baseline TcPO2 values at days 3, 14 and 30 after Iloprost infusion and needing of re-intervention (re-PTA) have been evaluated.. Twenty-five patients have been included, 12/25 (48%) in Group A and 13/25 (52%) in Group B. There were no significant differences at the baseline and one day after PTA between the two groups while TcPO2 values recorded in Group A at days 3, 14 and 30 after Iloprost infusion were significant higher in comparison to the Group B (χ = 0.005). The rate of re-PTA were respectively 33,3% (Group A) and 53,8% (Group B) (p = 0.03).. Iloprost may be an early predictor of successful revascularization in patients affected by critical limb ischemia (CLI) and DFUs.

Topics: Diabetes Mellitus; Diabetic Foot; Epoprostenol; Foot Ulcer; Humans; Iloprost; Ischemia

Topics: Diabetes Mellitus; Epoprostenol; Foot Ulcer; Humans; Iloprost; Ischemia; Limb Salvage

Previous studies demonstrated that early recoil is frequently observed in patients undergoing balloon angioplasty. The aim of this study was to evaluate the impact of intra-arterial administration of iloprost (Endoprost®, Italfarmaco S.p.A., Milan, Italy) on early elastic recoil after balloon angioplasty of below-the-knee (BTK) vessels in patients with critical limb ischemia (CLI).. Between January 2015 and December 2015 32 patients with CLI underwent balloon angioplasty of at least one BTK vessel followed by intra-arterial administration of iloprost. Early elastic recoil was defined as residual lumen compromise >10%. Early elastic recoil was determined on the basis of minimal lumen diameter (MLD) measurements at baseline (MLDbaseline), immediately after BTK balloon angioplasty (MLDpostdilation), and 15 minutes thereafter (MLD15min).. Patients were predominantly female (18/32, 56.2%) with a mean age of 79.6 years (range 68-87). Most of the patients were diabetics (25/32, 78.1%). An occlusion was present in 24 cases (75%). Mean BTK lesion length was 144.1 mm (range 22-320). Mean MLD measurements were 0.1 mm (range 0-0.5; MLDbaseline), 2.5 mm (range 1.9-3; MLDpostdilation), and 1.9 mm (range 0.7-3; MLD15min). Early elastic recoil was recorded in 14 patients (43.8%). The mean percentage of elastic recoil after 15 minutes was 21.4%.. In our experience intra-arterial administration of iloprost reduces the risk of early elastic recoil after balloon angioplasty of BTK vessels in patients with CLI. Further analyses with larger population studies and randomized trials are needed to validate this therapeutic option.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Critical Illness; Elasticity; Female; Humans; Iloprost; Injections, Intra-Arterial; Ischemia; Leg; Male; Peripheral Arterial Disease; Recurrence; Time Factors; Treatment Outcome; Vascular Patency; Vasodilator Agents

We report the case of a young woman who experienced ischemia of upper limb after osteopathic manipulation. Duplex and computed tomography scan showed wall hematoma of the ostium of subclavian artery. The patient spontaneously recovered so that no surgery was necessary. Dissection of vertebral and carotid arteries has been reported after osteopathic manipulations. We report ischemia of upper limb secondary to dissection of subclavian artery. Arterial dissections associated with manipulation should be recorded in a register in order to assess more carefully the vascular risk that this method carries.

Topics: Adult; Anticoagulants; Computed Tomography Angiography; Female; Hematoma; Heparin, Low-Molecular-Weight; Humans; Iloprost; Ischemia; Manipulation, Osteopathic; Subclavian Artery; Tinzaparin; Treatment Outcome; Ultrasonography, Doppler, Color; Upper Extremity; Vascular System Injuries; Vasodilator Agents

Case report of a patient with age-related macular degeneration whose digital ischemia can most plausibly be attributed to ranibizumab.. To report ranibizumab as the probable cause of digital ischemia in a patient treated for age-related macular degeneration.. Single-patient case report.. An 83-year-old woman with an unremarkable medical history suffered acute ischemia in her left hand with necrosis of the distal phalange of the fifth finger after six intravitreal injections of ranibizumab. Her etiological work-up was negative. Her condition improved after endovascular revascularization and remained good at six months' follow-up after three months of dual antithrombotic therapy (low molecular weight heparin then rivaroxaban, both with aspirin) followed by rivaroxaban alone and four courses of intravenous iloprost.. The increased incidence of peripheral arterial thromboembolic events in patients under ranibizumab treatment is slight but significant, with 0.8-5% of patients affected, most of which suffer strokes. These events seem to occur at a random time after ranibizumab treatment is initiated and no reliable marker has yet been identified. The most probable cause of digital ischemia in our patient was ranibizumab.

Topics: Aged, 80 and over; Angiogenesis Inhibitors; Angioplasty; Aspirin; Combined Modality Therapy; Female; Fingers; Heparin, Low-Molecular-Weight; Humans; Iloprost; Intravitreal Injections; Ischemia; Macular Degeneration; Radial Artery; Ranibizumab; Rivaroxaban; Thrombectomy; Thrombosis; Ulnar Artery; Vascular Endothelial Growth Factor A

Persistent or chronic intestinal ischemic injury (i3) can lead to severe malnutrition and acute mesenteric ischemia. Although recommended, revascularization of splanchnic arteries is sometimes unrealizable.. We report a case series of iloprost use in consecutive stable patients with persistent i3 unsuitable for revascularization followed in a tertiary care center. The feasibility of revascularization was discussed and ruled out by a multidisciplinary team, and informed consent was obtained prior to consideration of a vasoactive therapy. Therapeutic response was defined at 6 months by a decrease in the use of analgesic and parenteral nutrition, and no need for intestinal resection.. Between 2006 and 2015, 6 patients (mean age: 51) were included. Splanchnic vascular insufficiency was due to superior mesenteric artery (SMA) thrombosis (n = 4), dissection of the celiac trunk and SMA (n = 1), or repeated vasospasm resulting in chronic nonocclusive mesenteric ischemia (n = 1). Iloprost was delivered via continuous intravenous perfusion at a maximum dosage of 2 ng/kg/min for 6 hours/day on 4 consecutive days, without severe adverse events. Therapeutic response was observed in 4 patients, 3 of which completely stopped parenteral nutrition and analgesic with no need for intestinal resection.. Our results are consistent with findings of a favorable effect of iloprost in patients with persistent splanchnic ischemia that should be confirmed in prospective trials.

Topics: Analgesics; Databases, Factual; Female; Humans; Iloprost; Infusions, Intravenous; Intestines; Ischemia; Male; Middle Aged; Parenteral Nutrition; Retrospective Studies; Splanchnic Circulation; Tertiary Care Centers; Time Factors; Treatment Outcome; Vasodilator Agents

Proper management of patients with thromboangiitis obliterans (TAO) or cannabis-associated arteritis (CAA), presenting with critical lower limb ischaemia (CLI) remains controversial, and data are limited.. Patients with TAO or CAA presenting with CLI between 2011 and 2016 were retrospectively evaluated. Patients requiring primary intervention were excluded. Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100 mg twice/day) after discharge, and (c) strict recommendations/monitoring for smoking cessation. Main outcomes included symptom recession, ankle-brachial index (ABI) improvement, and healing of lesions at the time of discharge as well as amputation, revascularization, and abstinence rate during follow-up.. Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of the patients reported any other factor than smoking. All patients presented with rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at presentation was 0.46 ± 0.2, after 28 days of treatment, all patients showed improvement regarding clinical picture and ABI measurement (0.54 ± 0.1; p < 0.05). During follow-up, only three patients underwent bypass surgery and two patients underwent major amputation, although the smoking abstinence rate was very low (13 %).. Intravenous iloprost plus bemiparin for 28 days together with per os aspirin plus cilostazol seem to produce promising results in patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate. However, larger series are needed to further evaluate inter-group differences and potential prognostic factors.

Topics: Adult; Amputation, Surgical; Ankle Brachial Index; Anticoagulants; Arteritis; Aspirin; Cardiovascular Agents; Cilostazol; Critical Illness; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Iloprost; Infusions, Intravenous; Ischemia; Limb Salvage; Lower Extremity; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Smoking; Smoking Cessation; Tetrazoles; Thromboangiitis Obliterans; Time Factors; Treatment Outcome; Vasodilator Agents

Severe frostbite can result in devastating injuries leading to significant morbidity and loss of function from distal extremity amputation. The modern day management approach to frostbite injuries is evolving from a historically very conservative approach to the increasingly reported use of early interventional angiography and fibrinolysis with tPA. The aim of this study was to evaluate the results of our frostbite treatment protocol introduced 3 years ago.. All frostbite patients underwent first clinical and then Doppler ultrasound examination. Angiography was conducted if certain clinical criteria indicated a severe frostbite injury and if there were no contraindications to fibrinolysis. Intra-arterial tissue plasminogen activator (tPA) was then administered at 0.5-1mg/h proximal to the antecubital fossa (brachial artery) or popliteal fossa (femoral artery) if angiography confirmed thrombosis, as well as unfractionated intravenous heparin at 500 units/h. The vasodilator iloprost was administered intravenously (0.5-2.0ng/kg/min) in selected cases.. 20 patients with frostbite were diagnosed between 2013-2016. Fourteen patients had a severe injury and angiography was performed in 10 cases. The total number of digits at risk was 111. Nine patients underwent fibrinolytic treatment with tPA (including one patient who received iloprost after initial non response to tPA), 3 patients were treated with iloprost alone and 2 patients received neither treatment modality (due to contraindications). The overall digital salvage rate was 74.8% and the Hennepin tissue salvage rate was 81.1%. One patient developed a catheter-site pseudoaneurysm that resolved after conservative treatment.. Prompt referral to a facility where interventional radiology and 24/7 laboratory services are available, and the combined use of tPA and iloprost, may improve outcome after severe frostbite.

Topics: Adult; Aged; Angiography; Clinical Protocols; Disease Management; Female; Fibrinolytic Agents; Frostbite; Humans; Iloprost; Infusions, Intra-Arterial; Ischemia; Male; Middle Aged; Radiology, Interventional; Referral and Consultation; Thrombosis; Tissue Plasminogen Activator; Ultrasonography, Doppler; Vasodilator Agents; Young Adult

Topics: Adolescent; Age of Onset; Antiphospholipid Syndrome; Child; Female; Foot; Foot Ulcer; Humans; Iloprost; Ischemia; Raynaud Disease; Regional Blood Flow; Treatment Outcome; Vasoconstriction; Vasodilator Agents; Wound Healing

Promoting the paracrine effects of human mesenchymal stem cell (hMSC) therapy may contribute to improvements in patient outcomes. Here we develop an innovative strategy to enhance the paracrine effects of hMSCs. In a mouse hindlimb ischaemia model, we examine the effects of hMSCs in which a novel triple-catalytic enzyme is introduced to stably produce prostacyclin (PGI2-hMSCs). We show that PGI2-hMSCs facilitate perfusion recovery and enhance running capability as compared with control hMSCs or iloprost (a stable PGI2 analogue). Transplanted PGI2-hMSCs do not incorporate long term into host tissue, but rather they mediate host regeneration and muscle mass gain in a paracrine manner. Mechanistically, this involves long noncoding RNA H19 in promoting PGI2-hMSC-associated survival and proliferation of host progenitor cells under hypoxic conditions. Together, our data reveal the novel ability of PGI2-hMSCs to stimulate host regenerative processes and improve physical function by regulating long noncoding RNA in resident progenitor cells.

Topics: Animals; Cell Line; Cells, Cultured; Combined Modality Therapy; Cyclooxygenase 1; Epoprostenol; HEK293 Cells; Hindlimb; Humans; Iloprost; Ischemia; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice, Inbred NOD; Mice, SCID; Motor Activity; RNA, Long Noncoding; Running; Transplantation, Heterologous; Treatment Outcome; Vasodilator Agents

Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ.. A retrospective study enrolling 102 consecutive patients between 2004-2008, with clinical and instrumental (ultrasound, angiography, transcutaneous tensiometry of oxygen TcpO2 and carbon dioxide TcpCO2 in the affected and contralateral limbs) diagnosis of critical ischemia. All patients received the best medical therapy. Iloprost was administered (0.5-2 ng/kg/min 6 hours/day for 2-4 weeks) in all patients initially considered unsuitable for revascularization, repeating it regularly in time every six-twelve months in the case of positive response. The minimum expected follow-up was 4 years.. 71.5% of patients were treated with iloprost and the responder rate was 71.2%. Most of the patients were regularly retreated with repeated cycles. Initial median supine TcpCO2 in symptomatic limb was higher in untreated patients than those treated (58 vs. 49 mmHg; p < 0.05) and in non-responders compared to responders (60 vs. 49 mmHg; p < 0.05). TcpCO2 directly and significantly correlated with the highest risk of mortality and seems to represent a new accurate prognostic criterion of unfavourable short and long-term response to prostanoid. In iloprost group, major amputations were significantly reduced. Revascularization was significantly higher in non-responders (57.1% vs. 11.5%; p < 0.05). There was a significantly higher prevalence of subsequent myocardial infarction in the non-iloprost group (27.6% vs. 9.6%; p < 0.05). The survival rate of non-responders was higher than untreated up until the second year (76.2% vs. 62%; p < 0.05). At 4 years we found higher survival in patients treated with iloprost (64.3% vs. 41% in untreated; p < 0.05) and in responders (75% vs. 38.1% in non-responders; p < 0.05).. Our results confirm the favourable role of iloprost on the long-term outcome in patients with CLI. In particular, the maximum benefit is obtained in responder patients treated with multiple cycles of infusion.

Topics: Amputation, Surgical; Humans; Iloprost; Ischemia; Retrospective Studies; Time Factors; Treatment Outcome; Vasodilator Agents

Whether medical therapy alone may reduce the amputation rates in patients with chronic limb ischemia and who are unsuitable for revascularization is a controversial topic. In this study, we aimed to investigate the effects of 1 week infusion of iloprost in the treatment of patients with chronic limb ischemia.. Twenty-seven consecutive patients were included in the study. There were 23 men (85.2%) and 4 women (14.8%) with a mean age of 68.93 ± 14.84 years. Patients were considered eligible if they were unsuitable for surgical and endovascular revascularization. Follow-up was made on 10th day and 6th month and included ankle brachial index and clinical assessment.. Minor side effects occurred in four patients (16.0%), but the treatment was continued. In-hospital mortality occurred in one patient (4.0%). Another two patients died and four patients received amputation until follow-up (overall mortality 11.1%). There was significant increase in mean ankle-brachial index values between 1st day and 10th day (p < 0.001), between 1st day and 6th month (p < 0.001), and between 10th day and 6th month (p < 0.001).. One-week treatment with iloprost may provide both long lasting symptomatic benefit and may improve hemodynamic parameters, which were shown to predict future amputation.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Ankle Brachial Index; Chronic Disease; Critical Illness; Drug Administration Schedule; Endovascular Procedures; Female; Hospital Mortality; Humans; Iloprost; Infusions, Intravenous; Ischemia; Lower Extremity; Male; Middle Aged; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures; Vasodilator Agents

The internet provides the public with unregulated access to a wide range of medications. We present the case of a 43-year-old man who purchased oral tadalafil gel on the internet and injected it into his left radial artery. He presented 48 hours after injection with signs of ischaemia distal to the injection site requiring a combination of medical and surgical treatment. This unique case highlights the potential dangers of unregulated access to medication and the consequences of intravascular injection of oral gels.

Topics: Adult; Amputation, Traumatic; Anticoagulants; Carbolines; Fingers; Gels; Heparin, Low-Molecular-Weight; Humans; Iloprost; Injections, Intra-Arterial; Ischemia; Male; Phosphodiesterase 5 Inhibitors; Prescription Drug Misuse; Radial Artery; Tadalafil; Vasodilator Agents

The aim of this study was to investigate the effects of iloprost (I) on lung injury as a remote organ following skeletal muscle ischemia-reperfusion injury in a rat model.. Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in Group S (Sham). Ischemia reperfusion group (Group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 minutes. Group iloprost (Group I) received intravenous infusion of iloprost 0.5 ng/kg/min, without ischemia and reperfusion. Group I/R/I received intravenous infusion of iloprost 0.5 ng/kg/min immediately after 2 hours of ischemia. At the end of the study, lung tissue was obtained for determining total oxidant status (TOS) and total antioxidant status (TAS) levels, histochemical and immunohistochemical determination.. Diffuse lymphocyte infiltration was detected in immunohistochemical examination of lung tissue in Group I/R. The connective tissue around bronchi, bronchioles and vessel walls was found to be increased. Although minimal local lymphocyte infiltration was detected in some fields in Group I/R/I, the overall tissue was found to be similar to Group S. iNOS expression was significantly higher in Group I/R, when compared with Group S and significantly lower in Group I/R/I compared to Group I/R.TOS levels were significantly higher in Group I/R, when compared with groups S and I (p = 0.028, p = 0.016, respectively) and significantly lower in group I/R/I, when compared with Group I/R (p = 0.048). TAS levels were significantly higher in Group I/R, when compared with groups S, I (p = 0.014, p = 0.027, respectively) and significantly lower in Group I/R/I, when compared with Group I/R (p = 0.032).. These results indicate that administration of iloprost may have protective effects against ischemia reperfusion injury (Fig. 8, Tab. 1, Ref. 30)

Topics: Adult; Animals; Antioxidants; Humans; Iloprost; Ischemia; Lung Injury; Male; Muscle, Skeletal; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Vasodilator Agents

To assess the efficacy and of iloprost in the treatment of Buerger's disease.. In this prospective study, 158 patients with rest pain and/or ischemic ulcers from 17 clinics were administered 1 ng/kg/min intravenous iloprost for 28-days. The primary endpoint was complete healing without pain or major amputation at 24 weeks. The secondary endpoints were pain assessment, reduction in ulcer area, 50% reduction of the ulcer size, shift in the modified SVS/ISCVS clinical status grading scale, global assessment by the investigator and an independent observer at 4 and 24 weeks. The comparisons were carried out with the initial values. The final evaluation was carried out in 150 patients.. Complete healing rate was significantly better with iloprost treatment in comparison to the initial values at 24 weeks (<0.001). The secondary endpoints; complete healing rate, pain, the size of the ulcer, 50% reduction of the ulcer size, SVS/ISCVS grading scale, assessment by investigator, assessment by observer parameters were significantly better at 4 and 24 weeks (<0.001). The reduction of the ulcer size was significantly better when comparing 4th and 24th week values (<0.05).. The results of this independent study indicate that intravenous iloprost relieves ischemic symptoms efficiently in the acute phase Buerger's disease patients. Considering unsatisfactory results following surgical revascularisation and sympathectomy in Buerger's disease, prostacyclin analogues might be the first line treatment as long as complete abstinence from smoking is achieved.

Topics: Adult; Amputation, Surgical; Analysis of Variance; Chi-Square Distribution; Critical Illness; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Middle Aged; Pain; Prospective Studies; Smoking; Smoking Cessation; Smoking Prevention; Thromboangiitis Obliterans; Time Factors; Treatment Outcome; Turkey; Wound Healing

Topics: Bosentan; Botulinum Toxins, Type A; Calcium Channel Blockers; Education, Medical, Continuing; Endothelin Receptor Antagonists; Evidence-Based Medicine; Female; Fingers; Humans; Iloprost; Ischemia; Life Style; Middle Aged; Orthopedics; Phosphodiesterase 5 Inhibitors; Prostaglandins; Randomized Controlled Trials as Topic; Raynaud Disease; Scleroderma, Systemic; Sulfonamides; Vascular Resistance; Vasodilator Agents

The study was aimed at assessing feasibility of treatment of patients suffering from critical ischaemia of lower extremities with iloprost as compared to the basic therapy by means of pharmacoeconomic analysis. The findings of clinical studies and meta-analyses demonstrated that therapy with iloprost results in a pronounced clinical effect as compared with the basic therapy: significantly (p<0.005) decreasing the number of amputations above the knee joint (23% versus 39%) and more frequently decreasing the size of trophic ulcers (in 49% of cases versus 26%). This provides maintenance of the ability to work in part of patients and a decrease in the frequency of hospitalization, which in its turn results in decreased costs of treatment and indirect expenses.. The results of the carried out study show that with due regard for only direct costs economy from treatment with iloprost would amount to 1,544,556 Roubles per 100 patients. With additionally taking into account of indirect costs economy from using iloprost as compared with basic therapy increases to 25,689,11 Roubles per 100 patients.

Topics: Amputation, Surgical; Cost Savings; Cost-Benefit Analysis; Disease Management; Drug Costs; Economics, Pharmaceutical; Female; Hospitalization; Humans; Iloprost; Ischemia; Lower Extremity; Male; Medication Therapy Management; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Severity of Illness Index

Topics: Angiogenesis Inducing Agents; Child, Preschool; Combined Modality Therapy; Cross Infection; Debridement; Fatal Outcome; Fingers; Gangrene; Humans; Iloprost; Infant; Ischemia; Male; Meningitis, Meningococcal; Multiple Organ Failure; Nitroglycerin; Platelet Aggregation Inhibitors; Shock, Septic; Staphylococcal Infections; Toes; Tuberous Sclerosis; Vasodilator Agents

Thorascopic sympathectomy is a widely used procedure for the treatment of intractable palmar hyperhidrosis.. A 24-year-old woman who underwent thorascopic sympathectomy for hyperhidrosis in 2005 presented on more than 30 occasions with recurrent right distal upper limb ischaemia secondary to repetitive episodes of vasospasm. The patient did not have preoperative symptoms consistent with Raynaud's syndrome. We observed a reduction in the symptomatic relief offered by Iloprost treatment over a period of five years.. This is the first report of distal upper limb ischaemia following thorascopic sympathectomy. We highlight the development of resistance to repeated Iloprost infusions that we observed in this case.

Topics: Drug Resistance; Female; Humans; Hyperhidrosis; Iloprost; Infusions, Parenteral; Ischemia; Radiography; Recurrence; Spasm; Sympathectomy; Thoracoscopy; Treatment Outcome; Upper Extremity; Vascular Diseases; Vasodilator Agents; Young Adult

We report a case of acute compartment syndrome associated with the use of iloprost in the treatment of Buerger's disease. After a four-compartmental fasciotomy of the affected lower limb, the patient made a complete recovery.

Topics: Angiography, Digital Subtraction; Compartment Syndromes; Decompression, Surgical; Fasciotomy; Humans; Iloprost; Infusions, Intravenous; Ischemia; Lower Extremity; Male; Middle Aged; Thromboangiitis Obliterans; Treatment Outcome; Vasodilator Agents

A 36-year-old female with known bilateral carpal tunnel syndrome was admitted to hospital and given a steroid injection on the ulnar side in her right hand. She suffered immediate ischaemia of the 3rd, 4th, and 5th fingers. Imaging showed decreased flow in the 4th and 5th phalageal arteries. Treatment with iloprost infusion commenced 7 days after the injury, with moderate improvement and further managed with a carpal tunnel release. This case report sheds light on an unusual yet very important complication of carpal tunnel management.

Topics: Adrenal Cortex Hormones; Adult; Angiography, Digital Subtraction; Carpal Tunnel Syndrome; Female; Fingers; Humans; Iloprost; Injections, Intra-Articular; Ischemia; Ulnar Artery; Vasodilator Agents

A 70-year-old woman presented with a 7-day history of severe pain, paresthesia, oedema, acrocyanosis and punctate haemorrhagic lesions on her fingertips. The complaints began 2 days after the second cycle of a first-line chemotherapy consisting of cisplatin or carboplatin, and gemcitabine due to advanced urothelial carcinoma. At the fingertips of both hands, haemorrhagic and partly ulcerative lesions were found; these were attributed to vascular toxicity of gemcitabine. Therapeutically sympathicolysis by bilateral blockade of the brachial plexus was performed, accompanied by intravenous administration of the prostacyclin analog iloprost, fractionated heparin subcutaneously and oral therapy with corticosteroids and aspirin. Digital amputation could be avoided. Acral ischemia is a rare but probably underreported adverse effect of gemcitabine therapy and a potential source of misdiagnosis.

Topics: Aged; Antimetabolites, Antineoplastic; Deoxycytidine; Fatal Outcome; Female; Fingers; Gemcitabine; Humans; Iloprost; Ischemia; Magnetic Resonance Angiography; Necrosis; Urinary Bladder Neoplasms; Vasodilator Agents

Topics: Acute Disease; Aged; Angiography; Cardiovascular Agents; Humans; Iloprost; Ischemia; Male; Thrombolytic Therapy; Thumb; Tissue Plasminogen Activator

A single series of patients affected by systemic sclerosis (SSc) and cyclically treated with iloprost was reviewed in order to evaluate the incidence of digital ulcers (DUs) and to compare the characteristics between the patients with and without this painful and disabling vascular complication. The record charts of 85 SSc patients were revised. Ischemic DUs and scleroderma contracture ulcers were separately considered. Twenty-nine subjects developed ischemic DUs during the course of the disease; whereas, scleroderma contracture ulcers occurred in six subjects. Ischemic DUs were associated with younger age at scleroderma onset, a longer disease duration, a longer time delay from scleroderma diagnosis to iloprost therapy, a bigger skin involvement, the presence of joint contractures, a videocapillaroscopic late pattern, a history of smoking, and of corticosteroids therapy. After the exclusion of four subjects with concomitant peripheral arterial disease, a forward-stepwise logistic regression analysis showed that only four variables, i.e., age at scleroderma onset, delay in beginning iloprost therapy, history of smoking, and presence of joint contractures remained significantly associated with ischemic DUs. In a score reflecting the sum of these four risk factors, the prevalence of ischemic DUs increased progressively from the lowest to the highest value of the score. The predictivity of this model was evaluated by the receiver-operating characteristics curve, with an estimated area under the curve of 0.836 with 95% confidence interval from 0.736 to 0.937. All the patients with scleroderma contracture ulcers were characterized by both diffuse pattern of disease and positivity for anti-Scl70 antibody. In this retrospective study, scleroderma patients with ischemic DUs are characterized by early disease onset, delay in beginning iloprost therapy, smoking habit, and presence of joint contraction. A score reflecting the sum of these factors may be useful to predict the risk of developing ischemic DUs.

Topics: Female; Fingers; Humans; Iloprost; Ischemia; Male; Middle Aged; Raynaud Disease; Risk Factors; ROC Curve; Scleroderma, Systemic; Skin; Ulcer; Vasodilator Agents

Topics: Aorta; Celiac Artery; Female; Humans; Iloprost; Ischemia; Liver Circulation; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Mesentery; Middle Aged; Vasodilator Agents

The authors present the results of preoperative and postoperative prostacyclin analog treatment with skin grafting in a large ulceration of a chronic critical ischemic leg in a man who had lost his contralateral extremity 5 years ago. Healing was uneventful at the 6-month follow-up.

Topics: Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Male; Middle Aged; Skin Transplantation; Vasodilator Agents; Wound Healing

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

This study investigated the cytoprotective effects of N-acetylcysteine (NAC) and iloprost on spinal cord ischemia in an experimental model.. Thirty-five (male) New Zealand white rabbits were included in five study groups (n=7, each group). One group served as Sham. Rabbits in other groups had their abdominal aorta cross-clamped just above the iliac bifurcation for 40 min. During aortic cross clamping, iloprost, NAC, both iloprost and NAC or saline (control) were infused.. In NAC, iloprost, and iloprost+NAC groups, neurological status of rabbits (Tarlov score) 24 and 48 h after the operation was better than the control group (p<0.01), but worse than the Sham group (p<0.01). There was minimal neuronal damage in the iloprost treated groups compared to the NAC group (p<0.05). Mean viability index values in NAC, iloprost and iloprost+NAC groups were higher than the control group (p<0.01). Viability index in the NAC group was lower than the iloprost and iloprost+NAC groups.. The use of iloprost and NAC may provide better protection from spinal cord ischemia.

Topics: Acetylcysteine; Animals; Cytoprotection; Iloprost; Ischemia; Male; Models, Animal; Nitric Oxide; Paraplegia; Phosphopyruvate Hydratase; Rabbits; Random Allocation; Spinal Cord; Vasodilator Agents

Peripheral arterial vascular disease is caused by atherosclerosis. The severity of peripheral arterial disease is closely associated with the risk of myocardial infarction, ischemic stroke, and death from vascular causes. Approximately 1/3 of patients with peripheral disease have typical claudication. The goals of treatment for patients with claudication are to relieve their exertional symptoms, increase walking capacity, and globally improve their quality of life. In the peripheral arterial disease IIB stage, with claudication < 100 meters, no useful medical therapy is available. Aim of this investigation is to analyse, in a retrospective way, two groups of patients treated with vasodilator drugs or iloprost.. Data from 99 patients were registered: 79 patients were treated regularly with iloprost, administered for 10 days, 4 times a year. The 2nd group of 20 patients was treated with buflomedil 600 mg/die or pentoxifilline 1200 mg/die. The end point was the pain-free walking distance (PFWD) evaluated with treadmill test at basal conditions and at 3, 6, 12, 18 months.. Treatment groups showed no difference as for occurrence of by-pass surgery or endovascular procedures during follow-up. Improvement in PFWD was significantly more evident in patients treated with iloprost as compared with the control (P = 0.02). Even considering the PFWD variations at any follow-up step vs basal value, we always observed a statistically significant difference with iloprost, P < 0.0001.. The study suggests that iloprost may be effective in improving walking distance in severe IIB stage peripheral arterial vascular disease.

Topics: Adult; Exercise Test; Female; Humans; Iloprost; Ischemia; Leg; Male; Pentoxifylline; Pyrrolidines; Regional Blood Flow; Retrospective Studies; Vasodilator Agents; Walking

The aim of this study was to evaluate the capacity of transcutaneous partial pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to pharmacological treatment in short- and long-term follow-up of unreconstructable critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic and therapeutic algorithm able to define the possibility of prostanoid therapy in unreconstructable CLI at high risk of limb loss.. Twenty-six consecutive patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs) considered unreconstructable after peripheral angiography and with a history of type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3 weeks.. Transcutaneous gas-analytic monitoring (TGM) in non-reconstructable CLI treated with Iloprost divided patients into 2 groups: early responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who underwent a second cycle of Iloprost within a few months of the first, TGM further divided the patients into another subgroup of late responders (LR) with TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after pharmacological treatment failure, should undergo eventual surgical re-timing and/or spinal cord stimulation in a final attempt to save the limb.. In the short-term follow-up of CLI, a marked reduction in supine/dependent TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot proved to be significant predictors of major amputation risk. In the long-term follow-up period, TGM showed that, in ER and in LR, the favourable effect of pharmacological therapy observed in the first 6 months will disappear over the next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid therapy repeated every year. In NR treated with surgical and/or alternative therapies who did not undergo major amputations, prolonged instrumental TGM will provide a constant evaluation of metabolic parameters, thus providing the possibility to save the limb with additional pharmacological therapy.

Topics: Aged; Aged, 80 and over; Blood Gas Monitoring, Transcutaneous; Critical Illness; Female; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Time Factors; Vasodilator Agents

Iloprost, usually administered through intravenous infusion for 6 hours per day for at least 21 days, is the main medical treatment for critical limb ischemia in patients unsuitable for surgical or endovascular approach. We evaluated the tolerance and the short-term and long-term effects of a single 1-week treatment in critical limb ischemia patients.. Twenty-nine patients in Leriche-Fontaine III and IV stage were treated with iloprost infusions for 16 hours per day for 7 days, achieving a maximal dose of 1.5 ng/kg/min. Tolerance and clinical assessment after treatment discontinuation and after 1 and 6 months were recorded; clinical evaluation (rest pain, trophic lesions), ankle/brachial pressure index (ABPI) and treadmill exercise test were performed before, immediately after treatment and after 1 and 6 months.. No discontinuation of treatment occurred because of intolerance to iloprost. At the end of the treatment 69% of patients were responders, 55.2% at 1 month, 37.9% after 6 months. ABPI and treadmill maximum walking distance were improved by the treatment at every timepoint. After 6 months 10.3% mortality and 3.4% major amputation rates were recorded. There was a higher percentage of non-responders amongst women vs men, in diabetic patients vs non diabetic and in stage IV patients vs stage III.. One-week treatment with iloprost is safe and effective in both Leriche-Fontaine stage III and IV patients. Clinical effects are persistent over time, often lasting up to the 6th month, similarly to the commonly used 28-day treatment, with clear implications in terms of patient's compliance and medical cost containment.

Topics: Aged; Aged, 80 and over; Exercise Test; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Middle Aged; Vasodilator Agents

The association of vasoplegic shock and myocardial infarction in a patient under iloprost treatment for critical ischemia of the lower limbs has not previously been reported.. A 56 year-old man suffering from type 2 diabetes, hypertension and dyslipidemia developed critical ischemia of the right leg and was treated with iloprost. On the 19th day of infusion, he developed a vasoplegic shock with myocardial infarction. The shock resolved and he recovered from the infarction.. This case report indicates the need for reinforced blood pressure and electrocardiographic monitoring in diabetes patients treated with iloprost.

Topics: Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Myocardial Infarction; Shock, Cardiogenic; Time Factors; Vasodilator Agents

Topics: Diabetes Mellitus, Type 2; Diabetic Angiopathies; Gases; Humans; Iloprost; Ischemia; Leg; Platelet Aggregation Inhibitors; Treatment Failure; Treatment Outcome

We analysed our experience with the use of iloprost for the treatment of critical ischaemic digits (ID) in children with connective tissue diseases (CTD) in order to assess its safety and efficacy.. This was a retrospective analysis of paediatric patients with CTD who were treated with iloprost for critical ID resistant to conventional therapy. Information on demographics, clinical and laboratory features, the regimen of iloprost treatment and outcome were collected.. Fifteen patients (10 female, five male) treated one or more times with iloprost were included (total of 19 treatments). Six had juvenile systemic sclerosis, five had systemic lupus erythematosus, three had mixed connective tissue disease and one had cutaneous polyarteritis nodosa. Thirteen patients were already taking calcium channel blockers with no improvement; in two patients ID were the presenting signs of the disease without prior treatment. Eleven patients had more than two fingers involved; one child had involvement of all 10 fingers. Normal digital blood flow was achieved in 74% of treatments and significant improvement was noted in 26%. Fingertip necrosis was present in 11 patients (14 treatments). It healed completely in seven, improved in one and remained unchanged in six. Raynaud's phenomenon (RP) was present in 14 patients (17 treatments): in two no RP attack occurred during the follow-up period, eight improved both in the number of attacks per week and in the duration of each attack. Complete pain relief was observed in 10/17 treatments (59%) and there was a significant decrease in pain in the remaining seven. No major side-effects or withdrawal symptoms were reported. Minor side-effects reported include reversible headache (seven patients), hypotension or irritability (three), nausea/vomiting (two) and injection site reaction (one).. Iloprost appears to be a safe and effective treatment for ischaemic digits and digital ulcers in children with CTD. In conjunction with immunosuppressive drugs, it has a potential role in preventing irreversible complications, such as digital gangrene and amputation.

Topics: Adolescent; Child; Child, Preschool; Connective Tissue Diseases; Drug Administration Schedule; Female; Fingers; Humans; Iloprost; Infant; Infusions, Intravenous; Ischemia; Male; Retrospective Studies; Treatment Outcome; Vasodilator Agents

A 42-year-old man had ischaemia of three fingers of his left hand caused by thromboangiitis obliterans (Buerger's disease).

Topics: Adult; Diagnosis, Differential; Fingers; Humans; Iloprost; Ischemia; Male; Smoking; Thromboangiitis Obliterans; Vasodilator Agents

A 69-year-old amateur carpenter complained of a sudden stabbing pain and a white discoloration of D4 and D5 of the right hand while shoveling snow. On admission in our clinic twelve days later, clinical inspection showed a gangrene of the distal bone of D5 and proximal garland-shaped radial and ulnar subcutaneous haemorrhage and already ischemic contracture. D4 showed pale livid colour.. According to the results of an arteriography acral pulse oscillography revealed a occlusion of the digital arteries. Duplex sonography showed a thrombotic occluded aneurysm of the right ulnar artery over the hypothenar area.. Hypothenar hammer syndrome with a thrombotic occlusion of an aneurysm of the distal ulnar artery and multiple thromboembolic occlusions of the digital arteries of D4 and D5 of the right hand.. After initial therapy with Iloprost, treatment of pain and local treatment, an intraarterial locoregional lysis therapy with urokinase was performed. Acral blood circulation improved significantly and the patient was completely painless after treatment.. In case of an acute onset of unilateral digital ischemia hypothenar hammer syndrome should be considered. Regional thrombolysis can be performed in case of severe digital ischemia.

Topics: Acute Disease; Aged; Aneurysm; Angiography, Digital Subtraction; Fingers; Humans; Iloprost; Ischemia; Male; Plasminogen Activators; Platelet Aggregation Inhibitors; Syndrome; Thrombosis; Ulnar Artery; Ultrasonography, Doppler, Duplex; Urokinase-Type Plasminogen Activator; Vasodilator Agents

A 36-year-old patient presented with a severe hand ischemia after intraarterial injection of four dissolved tablets of Methylphenidate each 10 mg (Ritalin into the right radial artery.. Non-invasive vascular diagnostic demonstrated a normal perfusion of the radial and ulnar artery and a severe ischemia of the small vessels of the right hand.. Under suspicion of a combined vaso-spastic and thromboembolic arterial occlusion we started an intraarterial lysis therapy followed by anticoagulation with heparin and infusions of prostaglandines. Despite this therapy necroses of three fingers developed; partial amputation was followed by a good wound healing.. Ischemia of an extremity after intraarterial injection of drugs is a vascular emergency.

Topics: Acute Disease; Adult; Amputation, Surgical; Anti-Inflammatory Agents; Anticoagulants; Central Nervous System Stimulants; Drug Therapy, Combination; Emergencies; Fingers; Heparin; Humans; Iloprost; Injections, Intra-Arterial; Ischemia; Male; Methylphenidate; Necrosis; Platelet Aggregation Inhibitors; Prednisone; Prostaglandins; Radial Artery; Substance Abuse, Intravenous

In critical limb ischemia (CLI), the prognosis to keep the leg is poor if revascularisation is not possible. Treatment with prostanoids has proven to be beneficial regarding pain relief, ulcer healing and limb salvage but only in a proportion of patients. Prostanoids exert their effect in different ways e.g. on white blood cells and endothelial cells. No study has so far investigated the effect of prostanoids on the local tissue metabolism. The aim of this study was to investigate if infusion of the prostacyclin analogue, iloprost (PGI2) improves the local metabolism measured by microdialysis technique.. Eleven patients, 7 men and 4 women, median age 75 years (range 64-89 years), suffering CLI (Fontaine stage III and IV), were included. Patients with insulin dependent diabetes mellitus were excluded. Microdialysis catheters (CMA 60) were inserted subcutaneously in the ischemic leg and in the pectoral region, respectively. An iloprost infusion was given for 6 hours during 3 days preceded by a control day. Registrations of glucose and lactate levels were performed hourly.. No significant differences were found in lactate or glucose levels over the treatment period but a trend of increasing glucose and decreasing lactate was observed. Compared to the control day, lactate was significantly lower during (p=0.02) and after (p<0.05) the infusion. This was also true for the reference catheter during the infusion period (p=0.02).. No immediate improvement in glucose or lactate levels in ischemic tissue could be observed after 3 days of iloprost infusion, but a significant lactate decrease was found compared to a previous control day, suggesting a possible metabolic response.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Lactic Acid; Leg; Male; Microdialysis; Middle Aged; Treatment Outcome; Vasodilator Agents

Antithrombin (AT) supplementation in patients with severe sepsis has been shown to improve organ failures in which activated leukocytes are critically involved. However, the precise mechanism(s) for the therapeutic effects of AT is not well understood. We examined in rats whether AT reduces ischemia/reperfusion (I/R)-induced renal injury by inhibiting leukocyte activation. AT markedly reduced the I/R-induced renal dysfunction and histologic changes, whereas neither dansyl glutamylglycylarginyl chloromethyl ketone-treated factor Xa (DEGR-F.Xa), a selective inhibitor of thrombin generation, nor Trp49-modified AT, which lacks affinity for heparin, had any effect. Renal tissue levels of 6-keto-PGF(1 alpha), a stable metabolite of prostacyclin (PGI(2)), increased after renal I/R. AT enhanced the I/R-induced increases in renal tissue levels of 6-keto-PGF(1 alpha), whereas neither DEGR-F.Xa nor Trp49-modified AT had any effect. AT significantly inhibited I/R-induced decrease in renal tissue blood flow and the increase in the vascular permeability. Ischemia/reperfusion-induced increases in renal tissue levels of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and myeloperoxidase were significantly inhibited in animals given AT. Pretreatment of animals with indomethacin reversed the effects induced by AT. Iloprost, an analog of PGI(2), produced effects similar to those induced by AT. These observations strongly suggest that AT reduces the I/R-induced renal injury by inhibiting leukocyte activation. The therapeutic effects of AT might be mainly mediated by PGI(2) released from endothelial cells through interaction of AT with cell surface glycosaminoglycans.

Topics: 6-Ketoprostaglandin F1 alpha; Amino Acid Chloromethyl Ketones; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antithrombin III; Capillary Permeability; Drug Evaluation, Preclinical; Endothelium, Vascular; Epoprostenol; Factor Xa; Iloprost; Indomethacin; Ischemia; Kidney; Lymphocyte Activation; Male; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Specific Pathogen-Free Organisms; Tumor Necrosis Factor-alpha

The aim of this study was to assess the tolerance and report obtained results with a stable prostacyclin analogue (iloprost) in diabetic patients with severe forms of permanent lower limb ischaemia.. Sixty-four consecutive unselected patients, in stage III and IV of Leriche and Fontaine, turned down for vascular surgery after angiography and treated with iloprost during 28 days, were enrolled in this study. Patients were followed-up clinically (ischemic pain, trophic change, walking distance) and with transcutaneous oxymetry (D28). Long-term assessment (6 and 12 months) was expressed as rate of death, major amputation and of live patients with viable limbs and walking. There was no manifestation of intolerance to iloprost. Were considered as responders patients offering a lack or significant decrease in pain, a reduction of trophic lesions and improvement or recovery of walking.. Response at two months is lasting: 29 responders (45.3%) and 35 non-responders (54.7%). At 6 months and one year, we observed that 8 (12.5%) and 15 (24.1%) patients respectively had died; 19 (29.6%) and 22 (34.3%) patients underwent major amputation, but 41 (64%) and 34 (53.1%) patients were still alive with their limb and conservative walking. In responder group, at 6 months, 28 (96.5%) patients were alive without amputation for only 13 (37.1%) among non-responders. At one year, 79.3% of the responders and 31.4% of the non-responders were alive without amputation. A total loss of walking, a segmental amputation and a previous amputation of opposite limb were more often noted in no responder group. But no predictive factor was referred to TcPO(2) in particular. Results ware similar in the group of 136 non diabetic patients treated during the same period (67.9% alive with limb at 6 months).. This retrospective study, despite its limitations, underlines the clinical particularities of critical ischaemia in diabetics and the good tolerance to iloprost. This point allowed patients, in non-surgical chronic critical ischaemia, to avoid being confined to bed and to access to benefits of a early physiotherapy, in association with local treatment. However, no predictive criterion of long-term results could be established, except initial clinical severity and clinical change one month after treatment.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Diabetic Angiopathies; Female; Humans; Iloprost; Ischemia; Leg; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Treatment Outcome; Vasodilator Agents

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

Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P <0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

Topics: Adult; Aged; Cohort Studies; Female; Fingers; Humans; Hypertension, Pulmonary; Iloprost; Ischemia; Longitudinal Studies; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Raynaud Disease; Respiratory Function Tests; Scleroderma, Systemic; Skin; Ulcer; Vasodilator Agents

A 40-year-old man had chronic ischaemia of his replanted thumb. Angiography revealed occlusion of both digital arteries and weak collaterals. He was treated for 4 weeks with Iloprost which produced a definite and sustained improvement. As the digital arteries remained occluded, the beneficial effect of Iloprost was attributed to increased flow in the microcirculation and collaterals.

Topics: Adult; Amputation, Traumatic; Chronic Disease; Humans; Iloprost; Ischemia; Male; Replantation; Thumb; Vasodilator Agents

To evaluate the effect of an intravenously administered synthetic epoprostenol analog, iloprost, in nonocclusive acute mesenteric ischemia induced by cardiac tamponade.. Prospective, randomized, controlled experimental study.. Animal research laboratory at a university medical center.. Ten Yorkshire pigs (weight range, 20-25 kg).. Nonocclusive acute mesenteric ischemia was induced by pericardial tamponade. Pigs were randomized to receive either a low-dose, continuous intravenous infusion of iloprost (0.075 microg/kg/min) or an equivalent volume of normal saline to serve as the control. Infusion of iloprost or saline was continued after pericardial tamponade was reversed.. Ten anesthetized and ventilated pigs underwent laparotomy and thoracotomy. A pulmonary artery catheter was inserted, a magnetic flow probe was positioned around the superior mesenteric artery (SMA), and cannulation of the pericardial space was performed. Pericardial tamponade was induced by injecting 5% dextrose in water into the pericardial space until blood flow in the superior mesenteric artery decreased to half of baseline. After 60 mins, animals received either a continuous intravenous infusion of iloprost at 0.075 microg/kg/min (n = 6) or an equal volume of normal saline (n = 4) for 60 mins. Pericardial fluid was then removed, and iloprost or normal saline infusion was continued for another 60 mins.. Heart rate, blood pressure, cardiac output, oxygen delivery, oxygen consumption, SMA blood flow, ileal Pco2, ileal intramucosal pH, and serum lactate levels of mixed venous blood and mesenteric venous blood were recorded at baseline, after pericardial tamponade was induced, during the iloprost or normal saline infusion with pericardial tamponade, and after removal of pericardial fluid (reperfusion period).. Iloprost infusion increased SMA blood flow by 60% in this model of nonocclusive mesenteric ischemia (from 168 +/- 41 to 269 +/- 76 mL/min; p <.05). The effect of iloprost infusion was more prominent after the tamponade (422 +/- 87 mL/min in the iloprost group vs. 232 +/- 111 mL/min in the control group; p <.05). Increased mesenteric perfusion decreased intestinal mucosal hypercarbia, leading to improvement of intramucosal pH.

Topics: Animals; Cardiac Tamponade; Iloprost; Infusions, Intravenous; Ischemia; Random Allocation; Regional Blood Flow; Splanchnic Circulation; Swine; Vasodilator Agents

Iloprost given in a standard dose regimen (0.5-2 ng/kg/min for 6 hours daily over 21-28 days) has proven to be effective and safe in hospitalized patients with critical limb ischemia. Major drawbacks of the standard regimen are the high frequency of side effects, the long duration of the daily infusion, and a hospital stay of 3 to 4 weeks. Recently, the efficacy of low doses of iloprost (25 mg/day) was demonstrated. This open pilot study was undertaken to identify a more practical and cost-effective regimen with less side effects. The feasibility, efficacy and safety of an individually adapted, intermittently applied low-dose iloprost regimen in an outpatient setting were evaluated.. Twenty-seven patients with severe peripheral ischemia in the limbs or part of the limb due to various etiologies, who were eligible for outpatient treatment, were enrolled into the study. The infusion of iloprost (50 microg in 250 ml 0.9% saline) was started at 0.5 ng/kg BW/min and titrated to the individual optimum dose, which was defined as the maximum dose at which the patient felt entirely comfortable. The frequency of the iloprost infusions and the duration of the treatment were individually determined in each patient according to the severity of the clinical condition. Outcome endpoints were the response rates achieved by day 28, defined as substantial relief from rest pain and evidence of ulcer healing. The patients were followed up for a minimum of 6 months.. A total of 27 patients (15 male, 12 female, mean age 65 years) were treated. Twenty-four patients received daily infusions with a break at weekends (5 times/week); 3 patients were treated every second day (3 times a week). The mean daily iloprost dose actually given was 20+/-5 microg, the mean duration of treatment was 3.6+/-0.8 weeks, i.e. a mean of 17+/-4 infusions were administered. Six patients with one-vessel run-off underwent percutaneous transluminal angioplasty (PTA) of their single calf vessel. Twenty-six patients showed clinical improvement by day 28; excluding those who had had PTA, the response rate to iloprost was 74% (20/27). No patient required admission to hospital while receiving outpatient treatment; no side effects occurred after adjustment to the optimum dose. At long-term follow-up (11+/-3 months), 76% of patients were alive and had a viable limb.. In a limited number of patients with severe peripheral ischemia of various etiologies, long-term outpatient treatment with an individually adapted low-dose iloprost regimen was feasible and safe. Our data suggest that flexible treatment modalities might be as effective as rigid standard treatment regimens, the former being more advantageous in terms of greater practicability and cost-effectiveness due to outpatient management. Further studies are needed to confirm the efficacy of this individually adapted, low-dose outpatient iloprost treatment regimen in a larger number of patients.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Angioplasty, Balloon; Blood Pressure; Combined Modality Therapy; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Evaluation; Female; Follow-Up Studies; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Recurrence; Severity of Illness Index; Time Factors; Treatment Outcome

A 37-year-old man with ischaemic finger necrosis and recent-onset Raynaud's phenomenon associated with cocaine abuse is reported. Initial therapy with systemic vasodilators, low-molecular-weight heparin and aspirin failed. Resolution of the ischaemia and ulcer healing was rapidly achieved with intravenous infusions of the prostacyclin analogue iloprost. The mechanism of vascular ischaemic injury and the development of secondary Raynaud's phenomenon due to cocaine use is discussed.

Topics: Adult; Cocaine-Related Disorders; Fingers; Follow-Up Studies; Humans; Iloprost; Infusions, Intravenous; Ischemia; Male; Necrosis; Raynaud Disease; Risk Assessment

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

Surgical procedures on the thoracoabdominal part of the aorta make the spinal cord vulnerable to ischemia. Paraplegia is the most severe complication following thoracoabdominal operations. In this study, iloprost was used as an agent to decrease the severity of ischemia and reperfusion injury to the spinal cord during aortic occlusion and declamping.. Twelve adult mongrel dogs weighing 17+/-2 kg were used in this study. The animals were randomly assigned to either group I, which received saline solution (6 dogs), or group II, which received prostacyclin. Group I was referred to as the control group and group II as the iloprost group. After baseline measurements were completed, the aorta was cross-clamped for sixty minutes distal to the left subclavian artery. No pharmacologic agents were used to control blood pressure in group I. Proximal and distal mean arterial pressures (DMAP) were monitored continuously. DMAP were considered as diastolic pressure in preocclusion and reperfusion periods. Iloprost administration was started at a rate of 5 ng/kg/minute five minutes before the aortic occlusion. This dosage was increased to 25 ng/kg/minute during aortic occlusion.. Mean proximal arterial pressure was 147+/-12 mmHg in the control group and 116+/-13 mmHg in the iloprost group at occlusion (p<0.01). Mean distal arterial pressure was 19+/-7 in the control group and 37+/-5 in the iloprost group during clamping (p<0.05). Functional outcome was evaluated according to Tarlov scores 24 hours after the study. Although none of the animals recovered completely from the control group, 4 animals from the iloprost group recovered (p<0.05). Following the neurologic assessment, animals were sacrificed and specimens were taken for the electron microscopic study. Electron microscopic changes documented that severe mitochondrial damage and vacuolisation occurred in the control group. However these changes were more subtle in the iloprost group.. As a result of this study we concluded that iloprost infused before and during clamping of the thoracic aorta mitigates the spinal cord injury due to ischemia and reperfusion following unclamping.

Topics: Animals; Aorta, Abdominal; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Iloprost; Ischemia; Microscopy, Electron; Myelin Sheath; Reperfusion Injury; Spinal Cord; Vasodilator Agents

Currently available drug therapies for patients suffering severe ischaemia with rest pain and trophic lesions of the limbs remain unsatisfactory. Also vascular reopening procedures are suitable in only about half of the patients. In atherosclerotic disease when the vascular endothelium is damaged prostacyclin synthesis is decreased and thromboxane A2 production increases. Prompted by this knowledge of the importance of prostacyclin in pathogenesis of atherosclerotic disease an attempt was made to employ PGI2 clinically--for treatment of advanced forms of peripheral arterial atherosclerotic disease. Favourable effects of the stable analogue of prostacyclin (Iloprost), were reported in various studies, which included patients with peripheral atherosclerotic arterial disease, thromboangiitis obliterans and Raynaud's phenomenon. The use of Iloprost resulted in a significantly superior response than other drugs and placebo in terms of alleviation of rest pain, ulcer healing and decrease of amputation rate of ischaemic limbs. Therefore prostacyclin provides a therapeutic option in patients with advanced forms of arterial disease--including critical ischaemia.

Topics: Arteriosclerosis; Epoprostenol; Extremities; Humans; Iloprost; Ischemia; Raynaud Disease; Thromboangiitis Obliterans

Although the pathophysiology of critical limb ischaemia is poorly understood, there is evidence that the condition of the small arteries may determine the outcome of revascularization procedures. This study was designed to investigate the effects of critical limb ischaemia on the structure and function of the small arteries in the leg. Small arteries (<500 microm) from proximal (non-ischaemic) and distal (ischaemic) sites were obtained from patients undergoing bypass surgery for critical limb ischaemia and mounted in a myograph. Reactivity and morphological measurements were carried out and compared with controls. Control vessels from the thigh and calf showed no difference in media to lumen ratio. However, a comparison of ischaemic and non-ischaemic vessels from the patients with critical limb ischaemia showed significant thinning of the ischaemic vessel wall. Contraction studies using noradrenaline and angiotensin II revealed a significant decrease in the response of ischaemic vessels compared with the non-ischaemic vessels from the same patient. Moreover, these differences in reactivity were still apparent after the responses were corrected for wall thickness. Endothelial function assessed using the endothelium-dependent agonists acetylcholine and bradykinin showed a significantly impaired relaxation response to acetylcholine but not to bradykinin in the ischaemic vessels, and acetylcholine-induced relaxation was not improved after incubation with indomethacin. There was no change in the response to the endothelium-independent cAMP-mediated vasodilator iloprost but a significant impairment to sodium nitroprusside which acts via cGMP. These results suggest that small arteries in critical limb ischaemia are altered in both structure and function, with vessel wall thinning and impaired responses to acetylcholine and sodium nitroprusside.

Topics: Acetylcholine; Aged; Analysis of Variance; Angiotensin II; Arteries; Bradykinin; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Humans; Iloprost; In Vitro Techniques; Ischemia; Leg; Male; Middle Aged; Muscle, Smooth, Vascular; Nitroprusside; Norepinephrine; Vasoconstrictor Agents; Vasodilator Agents

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

Intraarterial injection may result in acute ischemia and amputation. The authors describe the case of a 27-year-old man with an acute hand ischemia following intraarterial injection of a suspension of buprenorphine. Despite its initial severity, this case was successfully treated with iloprost, a stable prostacyclin analogue, and dextran-40, a low-molecular-weight dextran.

Topics: Acute Disease; Adult; Anticoagulants; Buprenorphine; Dextrans; Hand; Humans; Iloprost; Infusions, Intravenous; Injections, Intra-Arterial; Injections, Intravenous; Ischemia; Male; Narcotics; Vasodilator Agents

Secondary postoperative ischaemia due to venous occlusion is the most detrimental insult to free microvascular flaps. In an experimental rat free flap model the efficacy of long acting prostacyclin analogues iloprost (Ilomedin) and cicaprost in venous occlusion induced postoperative ischaemia was studied. Free, microvascular groin flaps were transplanted to the neck and the draining veins were temporarily occluded on the first postoperative day for a total of 20 min. In the untreated control group, haemorrhagic flap necrosis occurred. Intravital microscopy after secondary ischaemia revealed flap areas without reperfusion. The functional vessel density was significantly reduced. Reperfused capillaries were tortuous and significantly dilated. After reperfusion the interstitial leakage of macromolecular dextran increased, indicating loss of microvascular endothelial integrity. Intraarterial and intravenous applications of iloprost were able to diminish the ischaemic effects, giving a flap survival rate of 83%. Similar results were obtained by intravenous and enteral administration of cicaprost. Transcutaneous oxygen partial pressure measurements confirmed the viability of the surviving flaps. We conclude that both iloprost and cicaprost are effective in preventing venous occlusion induced failure of free microvascular groin flaps.

Topics: Animals; Epoprostenol; Graft Rejection; Iloprost; Ischemia; Male; Oxygen; Partial Pressure; Postoperative Complications; Prostaglandins, Synthetic; Rats; Rats, Sprague-Dawley; Surgical Flaps; Vasodilator Agents

(1) Iloprost, a vasodilatory prostacyclin analogue administered by infusion, is indicated for second-line therapy in patients with severe ischaemia of the lower limbs, when surgical revascularisation fails or is contraindicated. (2) In thromboangiitis obliterans the clinical file on iloprost has remained inadequate since the product was first released. (3) A meta-analysis of 6 clinical trials giving conflicting results in patients with stage III or IV lower-limb arterial disease favoured iloprost. But the results of this meta-analysis are uninterpretable because of methodological biases. It is not known what effects iloprost has in the short term (on pain and skin damage) or in the long term (on the risk of amputation). (4) The iloprost dose must be adjusted individually according to adverse effects linked to vasodilation.

Topics: Clinical Trials as Topic; France; Humans; Iloprost; Ischemia; Leg; Meta-Analysis as Topic; Thromboangiitis Obliterans; Treatment Outcome; 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 physiological basis of postischemic hyperemia is not yet fully understood. The present study investigated the effects of pharmacologic manipulation of the prostaglandin system on local hemodynamics. Strain-gauge plethysmography was used to study 8 normal subjects and 9 patients with obliterating arterial disease of the lower limbs. Hemodynamic evaluations were performed before treatment, after seven days of low-dose acetylsalicylic acid (100 mg/day) to inhibit platelet thromboxane synthesis, and after acute infusion of 1 g of acetylsalicylic acid to inhibit endothelial prostacyclin synthesis. In patients with arterial disease, the hemodynamic study was also carried out after infusion of iloprost, a synthetic prostacyclin analogue. Acute infusion of acetylsalicylic acid significantly reduced basal blood flow in normal subjects, but not in patients with arterial disease. In the latter group, iloprost affected neither basal nor maximal postischemic flow. The study also evaluated the role of endothelin in musculocutaneous hemodynamic regulation, both in physiological conditions and in atherosclerosis. This part of the study addressed the possibility that the hemodynamic effects of vasodilator prostanoids like prostacyclin might affect endothelin release in vivo. During reactive hyperemia, plasma endothelin was reduced in normal subjects (-1.02 pg/mL, 95% CI: -2.23, 0.08), but not in patients with atherosclerosis (-0.35 pg/mL, 95% CI: -1.45, 0.75). In both groups, plasma endothelin was not affected by aspirin. These findings confirm the role of prostacyclin in local hemodynamic regulation. In the normal subject, musculocutaneous blood flow seems to depend at least in part on the action of vasodilator prostanoids and endothelin. This is not the case in patients with arterial disease, in whom plasma endothelin does not seem to be affected by postischemic changes in blood flow. A possible explanation for this difference could be alteration of the endothelial function in patients with arterial disease, related to the functional and structural characteristics of the artery wall in atherosclerosis.

Topics: Aged; Arteriosclerosis; Aspirin; Endothelins; Epoprostenol; Hemodynamics; Humans; Hyperemia; Iloprost; Ischemia; Leg; Middle Aged; Platelet Aggregation Inhibitors; Plethysmography; Regional Blood Flow; Vasodilator Agents

To determine the effects of the stable prostacyclin analog, iloprost, in a porcine model of endotoxin-induced mesenteric ischemia.. Prospective, experimental, randomized, controlled study.. Animal research laboratory at a university medical center.. Pigs were randomized to receive a constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of carrier solution (normal saline) 30 mins before being infused with endotoxin (100 microg/kg over 1 hr). The infusion with iloprost or carrier solution was continued for the duration of the experiment.. Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy during which a magnetic flowprobe was placed around the superior mesenteric artery and an ileal tonometer was inserted. Thirty minutes before they were infused with endotoxin, the animals were randomized to receive intravenous iloprost or normal saline. Endotoxin was infused centrally over a 60-min period. Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the start of the endotoxin infusion. Data were measured at the end of the endotoxin infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by the dosage of iloprost used in this experiment. After resuscitation, the cardiac output returned to baseline in the iloprost-treated group but remained decreased in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric blood flow increased 34% above baseline levels in animals pretreated with iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7 kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44 +/- .23) in the control group than in the iloprost-treated group.. Pretreatment with intravenous iloprost effectively increased intestinal blood flow in this model of endotoxin-induced mesenteric ischemia. This action of the drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose iloprost had no effect on mean arterial pressure, it may be a useful adjunct in the treatment of sepsis and septic shock.

Topics: Acidosis; Animals; Endotoxemia; Evaluation Studies as Topic; Hemodynamics; Iloprost; Intestines; Ischemia; Prospective Studies; Random Allocation; Splanchnic Circulation; Swine; Vasodilator Agents

Iloprost, a prostaglandin I2, is chemically stable and it has been successfully used by intravenous infusion in severe limb ischemia. Usually Iloprost is diluted in 0.9% sodium chloride solution and infused intravenously for six hours each day for 28 days in hospital.. In the present study after the first three days of infusion with a traditional pump in hospital, a home pump has been utilised for the infusion of Iloprost at home. This device allows the continue infusion of Iloprost at a flow rate of 2 ml/h for six days, then the pump is filled with a new solution. The home pump consists of a protective shell in polycarbonate (10 x 12 cm), 270 ml of volume, inside there is a balloon reservoir (3 membranes) which is filled with Iloprost. The structure of Iloprost does not change into the home pump as evidenced by HPLC studies and its continue infusion allows plasmatic high levels of its active isomers during the 28 days of therapy. In 30 patients, 25 men and 5 women (mean age 61 years) with Fontaine stage IIB (6), III (5) and IV (19) POAD Iloprost has been infused with the home pump. The follow-up period was 1 to 16 months.. The results have shown 4 major amputations and 1 death, in 9 patients complete pain relief and ulcer healing, and in 6 patients only improvement in relief of rest pain and ulcers.. All the patients appreciated this system of infusion because they had a normal life; in addition it is less expensive because the patients stay in hospital only 3 days.

Topics: Female; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Leg Ulcer; Male; Middle Aged; Vasodilator Agents

Topics: Adult; Arm; Brachial Artery; Female; Forearm; Humans; Iloprost; Infusions, Intra-Arterial; Ischemia; Platelet Aggregation Inhibitors; Radial Artery; Thrombosis; Ulnar Artery; Vasodilator Agents

A young woman with acute upper extremity edema and ischemia after intraarterial drug injection is presented. Unsatisfactory results from standard treatment were the reason for changing the therapy to temporary thrombolysis, which led to significant improvement. Some days later severe impairment forced another attempt at applying standard therapy, again unsuccessful. Only after continuous intraarterial infusion of Iloprost, a new improvement occurred and saving of the hand was possible. It became obvious that more effective therapeutic measures ought to be applied when severe hand ischemia following intraarterial drug injection is present.

Topics: Acute Disease; Adult; Azlocillin; Diabetes Mellitus; Female; Hand; Humans; Iloprost; Injections, Intra-Arterial; Ischemia; Radiography; Thrombolytic Therapy

A 34-year-old patient was treated with constant intravenous infusion of sulprostone because of postpartum hemorrhage from a hypotonic uterus. The arm in which sulprostone had been infused was painful 23 h after infusion. A day later, the arm was found to be blueish, edematous and extremely painful as a result of arterial spasm. The vasospasm was probably caused by accidental subcutaneous infusion of sulprostone as a result of a displaced intravenous catheter. A diagnosis of critical limb ischemia was made. Treatment with the prostacyclin-analogue iloprost resulted in full recovery. Critical limb ischemia as a serious complication of sulprostone has not been previously reported.

Topics: Adult; Arm; Diabetes, Gestational; Dinoprostone; Female; Fetal Membranes, Premature Rupture; Humans; Iloprost; Ischemia; Obstetric Labor, Premature; Postpartum Hemorrhage; Pregnancy; Vasodilator Agents

Topics: Adolescent; Adult; Extremities; Female; Humans; Iloprost; Injections, Intra-Arterial; Ischemia; Male; Substance Abuse, Intravenous

Intraarterial bolus treatment with the prostacyclin analogue iloprost appears to have a prolonged beneficial effect on femorodistal bypass graft flow which extends beyond the duration of its vasodilator properties. The effect of iloprost on the microcirculation rendered ischaemic over the time course of a distal bypass operation was investigated in this study without the use of fluorescent light.. A rat model was designed to allow prolonged direct observation of leukocyte-venular endothelial adhesion in a femorodistal bypass simulation. The extensor digitorum longus (EDL) muscle of 10 rats was subjected to two 30 minute periods of ischaemia by a non-venous occluding tourniquet and to simulate some of the changes of chronic ischaemia the adverse effect of ischaemia was accentuated by indirect electrical stimulation via the lateral popliteal nerve.. Intraarterial bolus treatment with iloprost significantly reduced the total numbers of leukocytes observed in EDL venules, and the numbers exhibiting evidence of adhesion by rolling or sticking to venule endothelium compared with saline controls at one hour post ischaemia. Ischaemia induced vasodilatation and reduced shear stress by a similar and significant amount in both groups.. Two periods of ischaemia and reperfusion similar to those which occur during bypass grafting resulted in changes in the distal microcirculation consistent with reperfusion injury. Intraarterial bolus treatment with iloprost prevented these leucocyte-endothelial changes. It appears iloprost may have a role in reducing leukocyte-induced reperfusion injury in femorodistal bypass surgery.

Topics: Animals; Cell Adhesion; Femoral Artery; Hemodynamics; Hindlimb; Iloprost; Ischemia; Leukocytes; Male; Muscles; Rats; Rats, Sprague-Dawley; Venules

The ability of the prostacyclin analogue iloprost to improve survival of ischemic experimental skin flaps was investigated. Unilateral island skin flaps based on the superficial inferior epigastric vessels were raised in 70 rats and subjected to varying lengths of primary ischemia. The flaps were divided into the following four groups: group I, no perfusion washout; group II, postischemic washout with lactated Ringer's solution; group III, postischemic washout with urokinase; and group IV, postischemic washout with iloprost. Flap survival rates for group IV were significantly higher than all other groups (p < 0.05). The primary ischemia time at which 50% of the flaps failed was 8.9 hours for group I, 9.5 hours for group II, 13.3 hours for group III, and 15.3 hours for group IV. This is the first study to investigate the effect of iloprost on skin flap survival. Iloprost was found to be significantly more effective than urokinase in salvaging ischemic experimental skin flaps.

Topics: Animals; Epoprostenol; Female; Graft Survival; Iloprost; Ischemia; Isotonic Solutions; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Ringer's Lactate; Skin; Surgical Flaps; Urokinase-Type Plasminogen Activator

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

The authors carried out an investigation on the "short" and "middle-term" effect of the prostanoid derivate iloprost on some molecular haemostatic markers in a group of peripheral vasculopathic patients with critical limb ischemia. The series consists of 10 patients (6 males, 4 females, age 52 +/- 5) suffering from peripheral obstructive vasculopathy at the III-IV stage by Fontaine. After overnight fasting, each patient was given an intravenous infusion of iloprost lasting six hours at the rate of 2 ng/kg/min and reaching approximately the global dosage of 50 gamma; before and after the infusion a venous blood sample was withdrawn; the experiment was repeated under the same conditions after a four week treatment with the drug administered daily at the same dosage. For each sample the plasma levels of betathromboglobulin (BTG) fibrinopeptide A (FPA), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-I) and D-dimer (D-D) (ELISA, methods, kits Boehringer) were measured. The basal values of BTG, FPA, tPA, PAI-I and D-D were significantly increased compared to those of a control group; after the iloprost infusion (acute effect) significant changes of the BTG, FPA, tPA and PAI-I were not found; D-D only showed a marked reduction (p < 0.05); after the four week treatment with infusion the basal values of BTG, FPA, tPA and PAI-I resulted almost unchanged; D-D only showed a marked reduction (p < 0.05) both as regards the basal value and those after the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Female; Fibrinolysis; Humans; Iloprost; Ischemia; Leg; Male; Peripheral Vascular Diseases

The purpose of this study was to establish the incidence of surgical amputation for critical leg ischaemia in New Zealand, and estimate the hospital, prostheses and indirect costs of this intervention. The cost of amputations was then compared with the cost of treating such patients with iloprost. The study was retrospective. Individual patient records relating to 1991 for both public and private hospitals were analysed. Unit costs relevant to 1991 were applied to the volume data of patients and procedures to derive total costs. Costs were estimated on an incremental basis taking a societal perspective. Conservative estimates were obtained for hospital costs, prostheses and for production loss (loss of output or productivity). Total cost was $NZ15.9 million (hospital and prosthesis cost $NZ13.1 million, production loss $NZ2.8 million). The total quantified cost per amputation was $NZ23 038 (hospital and prosthesis cost $NZ19 020, production loss $NZ4017). 32% of patients requiring amputations were in the working age group. The theoretical avoidance of amputation by treatment with iloprost resulted in net savings of hospital and prosthetic costs of between $NZ6660 and $NZ8720 per patient. Amputation for critical leg ischaemia is costly and has a high mortality, but for iloprost treatment to be cost effective in a New Zealand hospital setting, patients must be targeted and a success rate of at least 55% achieved in avoidance of amputation and reduction of pain while at rest.

Topics: Amputation, Surgical; Artificial Limbs; Cost of Illness; Cost-Benefit Analysis; Diagnosis-Related Groups; Hospital Costs; Humans; Iloprost; Incidence; Ischemia; Leg; New Zealand; Peripheral Vascular Diseases; Retrospective Studies

Free flap transplantations and replantations of extremities are threatened by venous occlusion in the postoperative course. In rats, free autogenous groin flaps were transplanted to the neck using microsurgical techniques. On the first postoperative day, the draining vein of the flap was temporarily clamped. In the control group there was always a total loss of the flaps by haemorrhagic necrosis. The intraarterial flap perfusion by iloprost during the clamping was able to diminish the ischaemic effects; 80% of the flaps survived. The systemic application of iloprost by intravenous infusion reduced the ischaemic effects in a similar way. Serious complications such as intraabdominal bleeding or bleeding in the donor area were seen after intravenous administration. Cicaprost had a similar protective effect on flap ischaemia after intravenous infusion. Flap survival was comparable to iloprost. Severe complications seemed to be less. Prostacyclin analogues were able to diminish damage of secondary ischaemia caused by venous occlusion.

Topics: Animals; Epoprostenol; Iloprost; Ischemia; Microsurgery; Rats; Surgical Flaps; Tissue Survival; Transplantation, Autologous

Thirty-four patients with ischaemic rest pain in 42 limbs and ankle pressure equal to or less than 50 mmHg have been treated with intravenous infusion of synthetic prostacyclin (iloprost) for eight days. Leg blood flow was measured with air plethysmography before treatment, on day 4 and day 8 of treatment. Total relief of pain for at least 6 weeks occurred in 91% of patients with leg blood flow > or = 40 ml/min, in 18% with leg flow 30-39 ml/min and in 11% with leg flow < 30 ml/min. Complete relief of pain for at least 6 weeks occurred in 92% of patients in whose limbs the blood flow on day 8 was greater than 50 ml/min but only in 6% with blood flow less than 50 ml/min. These results indicate that iloprost increases leg blood flow and that patients likely to respond can be identified from the baseline air plethysmographic measurement of leg blood flow.

Topics: Arteriosclerosis; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Plethysmography; Regional Blood Flow; Time Factors

The enhancement of blood flow in experimental skin flaps following postischemic perfusion washout was investigated in rats. Unilateral island skin flaps based on the superficial epigastric vessels were raised and subjected to 6 hr of primary ischemia. Group 1 was designated as a control and did not undergo postischemic perfusion washout. In the remaining rats, postischemic washout was performed with one of five agents: Group 2--lactated Ringer's solution; Group 3--University of Wisconsin solution, an organ preservation medium; Group 4--verapamil, a calcium channel blocker; Group 5--urokinase, a thrombolytic agent; Group 6--iloprost, a stable prostacyclin analog. Two hours following perfusion washout, fluorometric analysis revealed a statistically significant enhancement of blood flow in Groups 4, 5, and 6, compared to Groups 2 and 3 (p < 0.05). Furthermore, a significant increase in skin surface fluorescence was demonstrated in all the flaps that underwent perfusion washout, compared to the control flaps (p < 0.05). By analyzing skin surface fluorescence, the enhancement of nutritive blood flow in flaps, following postischemic perfusion washout, was evaluated. This is the first study in which the above pharmacologic agents were compared in a quantitative manner.

Topics: Adenosine; Allopurinol; Animals; Female; Fluorescein; Fluoresceins; Glutathione; Iloprost; Insulin; Ischemia; Organ Preservation Solutions; Perfusion; Raffinose; Rats; Rats, Sprague-Dawley; Skin; Surgical Flaps; Tissue Preservation; Urokinase-Type Plasminogen Activator; Verapamil

A 35-year-old drug abuser inadvertently injected adulterated heroin into her left femoral artery and presented with critical ischaemia of her left leg. Treatment with intravenous Iloprost, a stable prostacyclin analogue, combined with Heparin, produced a dramatic improvement in her circulation within 4 h.

Topics: Adult; Blood Pressure; Drug Therapy, Combination; Female; Femoral Artery; Heparin; Heroin; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Substance Abuse, Intravenous

We investigated the cytoprotective effects of verapamil, a Ca channel blocker, and of iloprost (ZK 36374), a stable prostacyclin analogue, on ischemia/reperfusion (I/R) injury in Wistar albino rat kidneys that were subjected to 60 min of warm ischemia and reperfusion. The groups included sham, ischemia-untreated (ISCH), verapamil-treated (VER), iloprost-treated (ILO), and verapamil + iloprost (VER + ILO)-treated rats. The 7-day survival of all the treated groups was better than that of the ISCH group. The creatinine concentration on the 3rd day was significantly lower in the VER + ILO group than in the ISCH group. Serum creatinine on day 3 was also low in the VER + ILO groups compared to the ISCH group, although the differences were not significant. The creatinine values on day 7 were significantly lower in the VER and ILO group than in the control, VER, or ILO groups. The malondialdehyde (MDA) concentrations of the kidney cortex tissue after reperfusion in all groups were higher than normal. The tissue-reduced glutathione (GSH) concentrations of the kidneys sampled immediately after reperfusion were significantly lower in the ISCH group than in all of the other treated groups. These results indicate that although verapamil and iloprost have independent cytoprotective effects on 60-min warm ischemia/reperfusion injury of rat kidneys, the protection afforded when both drugs are combined is synergistic. The mechanism of cytoprotection is not limited to the suppression of lipid peroxidation, and a nearly complete protection of reperfusion injury can be obtained by such an intervention.

Topics: Animals; Creatinine; Glutathione; Iloprost; Ischemia; Kidney; Male; Malondialdehyde; Rats; Rats, Wistar; Reperfusion Injury; Verapamil

Cholesterol embolisation is a little known complication of aortic surgery and radiological procedures with a mortality of 81%. Treatment has been poorly described and inadequate. We report a case in which we have followed an aggressive policy of treatment using modern vascular techniques not previously described in this condition.

Topics: Angiography; Aorta, Abdominal; Arteriovenous Fistula; Blood Vessel Prosthesis; Cholesterol; Combined Modality Therapy; Drug Therapy, Combination; Embolism; Femoral Artery; Humans; Iloprost; Injections, Intra-Arterial; Intermittent Claudication; Ischemia; Leg; Male; Middle Aged; Postoperative Complications; Pulse; Reoperation; Streptokinase

Topics: Adult; Antiphospholipid Syndrome; Female; Follow-Up Studies; Humans; Iloprost; Ischemia; Male; Middle Aged; Necrosis; Pain; Toes

Four uremic patients with advanced peripheral arterial occlusive disease (PAOD) of lower limbs causing rest pain and ischemic-necrotic lesions were treated with a four-hour intravenous infusion of iloprost at doses of 0.75-2.5 ng/kg/min for twenty-eight days. After a week of the therapy all patients experienced disappearance of rest pain and prolonged walking distance. At the end of the trial a diabetic patient showed a complete regression of the necrotic areas of two toes while the other patients still showed ischemic-necrotic foot lesions that were well demarcated. Iloprost therapy can be effective in uremic patients with severe PAOD.

Topics: Acute Disease; Arm; Drug Evaluation; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Necrosis; Remission Induction; Toes; Uremia

Earlier workers have suggested a possible fibrinolytic effect using prostaglandin or prostaglandin analogues. Despite using maximum tolerated doses of the prostaglandin analogue Iloprost, we have been unable to demonstrate any significant effect on fibrinolysis in patients with stage IV peripheral vascular disease (Fontaine classification).

Topics: Fibrinolysis; Humans; Iloprost; Ischemia; Necrosis; Peripheral Vascular Diseases; Skin Diseases

Pharmacokinetics of a single intra-graft infusion of 3000ng iloprost during femoro-crural bypass surgery have been investigated. Plasma iloprost concentrations, biphasic half-lives, and total drug clearances were found to occur within ranges demonstrated for IV infusion dose regimens.

Topics: Aged; Female; Femoral Artery; Humans; Iloprost; Infusions, Intravenous; Ischemia; Leg; Male; Middle Aged; Regional Blood Flow; Saphenous Vein; Transplantation, Autologous

This study of the postischemic events in the hamster cheek pouch showed that there is an increase in number of leukocytes adhering to the venular endothelium after reperfusion. It also showed that the stable prostacyclin analogue Iloprost could counteract both the postischemic increase in leukocyte adhesion and the postischemic increase in vascular permeability to macromolecules. The hamsters were anesthetized and the cheek pouch was everted and prepared for intravital microscopy. Temporary ischemia (30 min) was obtained using an expandable cuff placed around the proximal part of the cheek pouch. Fluorescein labelled dextran (FITC-dextran, Mw 150,000) was used as a tracer of macromolecular leakage from the postcapillary venules. Iloprost, given either topically (0.1 nM) or as an intravenous infusion (40 ng/kg/min), reduced the postischemic permeability increase (P less than 0.05) but did not affect the hemodynamics or the permeability response induced by histamine. It is proposed that these effects could be due to inhibition of leukocyte activation by Iloprost, indicating that these cells could play a role in the permeability increase during reperfusion after ischemia.

Topics: Animals; Blood Pressure; Capillary Permeability; Cell Adhesion; Cheek; Cricetinae; Histamine; Iloprost; Ischemia; Leukocytes; Male; Mesocricetus; Mouth Mucosa; Regional Blood Flow

Digital ischaemia is a recognised complication of both malignant disease and chemotherapy. Its onset may prevent further treatment and lead to tissue loss. We report a case of severe digital ischaemia in a patient with advanced breast carcinoma undergoing cytotoxic chemotherapy. This was successfully treated with Iloprost, a prostacyclin analogue.

Topics: Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Combined Modality Therapy; Female; Fingers; Fluorouracil; Humans; Iloprost; Infusions, Intravenous; Ischemia; Middle Aged

Heparin-associated thrombocytopenia and thrombosis is a severe complication of systemic heparin therapy. Its treatment is mainly based upon discontinuation of heparin therapy. However in some patients requiring emergency cardiac or vascular surgery, reexposure to heparin may be unavoidable. We report the management of two such patients by use of antiplatelet drugs for a vascular procedure. In the two cases, a combination of iloprost, a stable prostacyclin analogue (1 to 2 ng/kg/mn) with aspirin and dipyridamole was shown to inhibit ex vivo the heparin-induced platelet aggregation. These antiplatelet agents were continued during the perioperative period. A successful vascular procedure was achieved with full heparinization without subsequent thrombocytopenia or thrombotic or hemorrhagic complications. This experience supports the hypothesis that heparin can be readministered early to patients with heparin-associated thrombocytopenia and thrombosis, provided antiplatelet therapy is given.

Topics: Aged; Aorta, Abdominal; Aspirin; Dipyridamole; Female; Femoral Vein; Heparin; Humans; Iliac Artery; Iliac Vein; Iloprost; Ischemia; Platelet Aggregation; Platelet Aggregation Inhibitors; Thrombocytopenia; Thrombosis; Vena Cava, Inferior

Topics: Animals; Cardiovascular Agents; Ear; Epoprostenol; Iloprost; Ischemia; Mice; Mice, Hairless; Necrosis; Perfusion; Vascular Diseases

Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified.

Topics: Animals; Capillary Permeability; Diphosphates; Iloprost; Ischemia; Male; Microcirculation; Muscles; Radionuclide Imaging; Rats; Rats, Inbred WF; Reperfusion; Technetium; Technetium Tc 99m Pyrophosphate; Time Factors

Operative trauma, ischemia, release of catecholamines and thermal stimuli in consequence of harvesting, preservation and transplantation deteriorate the renal capillary circulation. By crossing of tolerance limits arises an irreversible transplant damage. The conditions of our examinations were placed in this field. By pre- and postischemic application of Iloprost was demonstrable an improvement of the ischemic tolerance of the kidney. Correction of renal hemodynamics, antiplatelet action and cytoprotection are the reasons of the protective influence of Iloprost in our opinion.

Topics: Acute Kidney Injury; Animals; Creatinine; Hemodynamics; Iloprost; Ischemia; Kidney; Kidney Transplantation; Rabbits; Swine

Topics: Cardiovascular Agents; Epoprostenol; Extremities; Humans; Iloprost; Ischemia; Raynaud Disease

Thromboxane, prostacyclin and their ratio could play an important role in the ischemic liver injury. To study this hypothesis, thromboxane and prostacyclin were measured by RIA after incubation of liver tissues removed during and after an ischemia of 90 min in male Wistar rats. The thromboxane to prostacyclin ratio increases during this period. In order to examine if this change could influence the survival rate of animals submitted to the same period of ischemia, drugs able to reduce the relative predominance of thromboxane were infused. The survival rate was not modified by administration of Iloprost or Daltroban, the antagonist of the thromboxane receptors. By contrast, imidazole, an inhibitor of thromboxane synthetase, significantly increased the survival rate. The same result was obtained with the administration of Daltroban plus Iloprost, suggesting that the reduction of thromboxane action associated with the increase of PGI2 level reduces the ischemic injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Epoprostenol; Iloprost; Imidazoles; Ischemia; Liver; Male; Phenylacetates; Rats; Rats, Inbred Strains; Sulfonamides; Thromboxane B2

The recovery of coronary flow and cardiac work was studied in isolated guinea pig hearts (working-heart preparation) after successive bolus injections of leukotriene D4 (LTD4) at increasing doses (0.01-1,000 ng). LTD4 caused an immediate (within 1 min) reduction in coronary flow and cardiac work and an increase in myocardial NADH fluorescence. There was limited spontaneous recovery at any dose and at the end of the cumulative LTD4 study, coronary flow recovered only from 41.4 +/- (SE) 3.5 (n = 10) to 53.5 +/- 4.7% of initial values, and cardiac work recovered from 21.2 +/- 4.1 to 33.1 +/- 5.6% (P less than 0.05). Adenosine (1 X 10(-6) M) or iloprost (1 X 10(-7) M) restored coronary flow but not cardiac work after LTD4 injections, in contrast to full recovery of cardiac work observed in hearts subjected to a similar degree of ischemia induced by reducing the coronary flow by a peristaltic pump, or hypoxia caused by reducing PO2 of the perfusion fluid. Adenosine (1 X 10(-6) M) and forskolin (1 X 10(-6) M) in combination, or iloprost (1 X 10(-7) M) and isoproterenol (1 X 10(-8) M) in combination, restored both coronary flow and cardiac work to control levels. Myocardial NADH levels, which increased immediately after LTD4 injections, returned to normal after perfusion with adenosine or iloprost. The data suggest that LTD4 has a prolonged vasoconstrictive effect on the heart. Reversal of this effect by compounds that stimulate adenylate cyclase of the vascular tissue (adenosine, prostacyclin) revealed a direct suppressive effect on the myocardium independent of the vascular effect and myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Adenylyl Cyclases; Animals; Colforsin; Enzyme Induction; Epoprostenol; Fluorometry; Guinea Pigs; Heart; Iloprost; Ischemia; Male; Myocardium; NAD; Oxygen Consumption; SRS-A; Vasoconstriction

Topics: Animals; Dinoprostone; Epoprostenol; Iloprost; Ischemia; Liver; Liver Circulation; Organ Preservation; Prostaglandins E; Rats; Splanchnic Circulation; Superoxide Dismutase; Temperature; Verapamil

Kidneys of five pigs were preoperatively perfused with iloprost in situ (infusion of 0.5 microgram X kg-1 for 15 minutes) and exposed to a warm ischemic period of 45 minutes. The behaviour of these kidneys during initial perfusion by gravity and hypothermic mechanical perfusion for 24 hours was comparable to that of kidneys having had a warm ischemic period of less than 5 minutes. After retransplantation all kidneys showed a sufficient blood flow and immediate production of urine during the test period of 3 hours.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Epoprostenol; Iloprost; Ischemia; Kidney; Kidney Transplantation; Kinetics; Renal Artery; Renal Circulation; Swine; Tissue Preservation; Vascular Resistance

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

Topics: Adult; Cardiovascular Agents; Diabetic Angiopathies; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Male