iloprost and Acute-Disease

Inhaled iloprost is attracting growing interest as a potential alternative and/or adjuvant to inhaled nitric oxide in the management of pediatric pulmonary hypertension in the acute and intensive care settings. However, there are currently no formal evidence-based guidelines regarding the use of inhaled iloprost in children with pulmonary hypertension. The aim of this systematic review is to assess the literature concerning the use of inhaled iloprost in children with pulmonary hypertension in the acute setting.. Studies were identified from PubMed and Embase. Internal literature databases and recent congress abstracts (2009 onward) were also searched for relevant publications.. Studies were included if they examined the use of inhaled iloprost in children with pulmonary hypertension in an acute or intensive care setting.. Twenty-eight studies were included in the review. The majority were case studies or case series (n = 17), and in total, the 28 studies represented the treatment of 195 children with iloprost. Iloprost was most frequently studied in children undergoing cardiac surgery (as a bridge to surgery and postoperatively), in children undergoing acute pulmonary vasoreactivity testing, and in neonates with persistent pulmonary hypertension of the newborn. The results of the included studies suggested that inhaled iloprost may have a diverse role in the acute treatment of pediatric pulmonary hypertension and that its acute effects are similar to those of inhaled nitric oxide. However, the iloprost dose was not consistently reported and varied greatly between studies, and several different administration devices were used.. Inhaled iloprost may be useful in the acute treatment of children and neonates with pulmonary hypertension, but clinical data are scarce, and the appropriate dosing of iloprost in different scenarios is uncertain. Well-designed prospective clinical trials are needed.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Child; Child, Preschool; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Vasodilator Agents

In the pediatric population, pulmonary hypertension may present as an acute event in the setting of lung or cardiac pathology or as a chronic disease, mainly as idiopathic pulmonary hypertension or associated with congenital heart disease. Recently, new pharmacologic approaches have demonstrated significant efficacy in the management of adults with pulmonary arterial hypertension; these include intravenous epoprostenol, prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. The same treatment strategies are currently used in children. There are only few reports of the use of inhaled iloprost in pediatrics, only one of which reported the use of chronic inhaled iloprost in a significant number of children. This report showed that 1) the acute pulmonary vasodilator response to inhaled iloprost is equivalent to that of inhaled nitric oxide; 2) acute inhalation of iloprost can induce bronchoconstriction 3) the addition of inhaled iloprost can reduce the need for intravenous prostanoid therapy in some patients; 4) most children tolerated the combination of inhaled iloprost and endothelin receptor antagonist or phosphodiesterase inhibitors; 5) Several patients had clinical deterioration during chronic inhaled iloprost therapy and required rescue therapy with intravenous prostanoids. In this review we will discuss the role of inhaled iloprost in acute and chronic pulmonary hypertension in children.

Topics: Acute Disease; Administration, Inhalation; Adult; Antihypertensive Agents; Child; Chronic Disease; Drug Therapy, Combination; Humans; Hypertension, Pulmonary; Iloprost; Treatment Outcome; Vasodilator Agents

Detection of pulmonary vasoreactivity is important for the evaluation of patient with pulmonary arterial hypertension (PAH). The present study aimed to investigate the acute hemodynamic responses to adenosine and iloprost in patients with congenital heart defects (CHDs) and severe PAH.. From Mar 2007 to Nov 2009, 75 patients with severe PAH secondary to left-to-right shunt CHDs underwent acute vasodilator test using aerosolized iloprost (n = 50) or intravenous adenosine (n = 25). The hemodynamics were detected and analyzed.. Decreased mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) were observed in 39 and 43 patients in the iloprost group, and in 16 and 19 patients in the adenosine group, respectively. However, the mean PAP was higher than 40 mm Hg in both groups. No significant difference was observed in the age and baseline hemodynamics between the patients with the decrease of PVR and mean pulmonary-to-aortic pressure (Pp/Ps) ratio greater than 10% and the remaining patients. Adenosine decreased both PAP and systemic arterial pressure significantly, while iloprost inhalation selectively reduced the PAP and increased the oxygen saturation of femoral arterial blood and the pulmonary-to-systemic flow (Qp/Qs) ratio. Compared with adenosine, iloprost caused a more profound decline in the Pp/Ps ratio, PVR and pulmonary-to-systemic vascular resistance ratio, and increase in the Qp/Qs ratio.. The acute haemodynamic responses to adenosine and iloprost varied among the patients with CHDs and severe PAH. Different to adenosine, inhaled iloprost exerted selective pulmonary vasodilative effects and was beneficial for pulmonary gas exchange.

Topics: Acute Disease; Adenosine; Administration, Inhalation; Adolescent; Adult; Child; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Severity of Illness Index; Young Adult

Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension.. In this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 +/- 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 microg) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system.. During pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 +/- 0.7 versus 3.7 +/- 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 +/- 0.3 versus 1.2 +/- 0.5 mmHg/ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 +/- 12 versus 70 +/- 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 +/- 0.5 versus 3.4 +/- 0.8 mWatt.s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 +/- 0.33 versus 1.03 +/- 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic nervous system.. In animals with acute pulmonary hypertension, inhaled iloprost improved global haemodynamics primarily via selective pulmonary vasodilatation and restoration of left ventricular preload. The reduction in right ventricular afterload is associated with a paradoxical decrease in right ventricular contractility. Our data suggest that this reflects an indirect mechanism by which ventriculo-vascular coupling is maintained at the lowest possible energetic cost. We found no evidence for a direct negative inotropic effect of iloprost.

Topics: Acute Disease; Administration, Inhalation; Animals; Cardiac Output; Disease Models, Animal; Hypertension, Pulmonary; Iloprost; Prospective Studies; Sus scrofa; Ventricular Function, Left; Ventricular Function, Right

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

Coronary reocclusion complicates the thrombolytic therapy of acute myocardial infarction despite the routine use of aspirin. This is consistent with experimental studies demonstrating that multiple agonists, in addition to thromboxane A2, mediate the platelet activation underlying reocclusion. Consequently, a more potent antiplatelet therapy with a broader spectrum of activity than aspirin may be required in this setting. Prostacyclin and its more stable analogue, iloprost, inhibit platelet aggregation to all known agonists and exert an additional effect over aspirin alone. Experiments in animal models have demonstrated, however, that iloprost increases the clearance of tissue-type plasminogen activator (t-PA) and impairs thrombolysis in vivo. This study examines whether a similar interaction occurs in humans.. Twelve patients with acute myocardial infarction received t-PA intravenously, 60 mg in the first hour and a maintenance infusion of 13.3 mg/hr for 3 hours. Patients were assigned in a double-blind fashion to iloprost (2 ng/kg/min) or placebo following the initial 90 minutes of the maintenance infusion of t-PA. Iloprost decreased mean arterial blood pressure (-10 +/- 2.9 mm Hg, p less than 0.05) but did not alter heart rate. Steady-state plasma iloprost concentration was 591 +/- 64 pmol/l. At this concentration, iloprost markedly inhibited platelet aggregation in vitro, particularly in the presence of aspirin. Steady-state clearance of t-PA was unchanged by iloprost (454 +/- 65 versus 443 +/- 136 ml/min in controls, p = NS). Furthermore, neither elimination kinetics nor plasma protein binding of t-PA was altered by iloprost.. At plasma levels that exert a potent antiplatelet effect, iloprost did not alter the pharmacokinetics of t-PA in men. Prostacyclin analogues may prove useful as an adjunct to plasminogen activators, particularly in patients at high risk for thrombotic reocclusion.

Topics: Acute Disease; Enzyme-Linked Immunosorbent Assay; Hemodynamics; Humans; Iloprost; Male; Myocardial Infarction; Placebos; Platelet Aggregation; Platelet Aggregation Inhibitors; Tissue Plasminogen Activator

Acute pulmonary hypertension (PH) complicates the course of several cardiovascular, pulmonary and other systemic diseases in children. An acute rise of RV afterload, either as exacerbating chronic PH of different aetiologies (eg, idiopathic pulmonary arterial hypertension (PAH), chronic lung or congenital heart disease), or pulmonary hypertensive crisis after corrective surgery for congenital heart disease, may lead to severe circulatory compromise. Only few clinical studies provide evidence on how to best treat children with acute severe PH and decompensated RV function, that is, acute RV failure. The specific treatment in the intensive care unit should be based on the underlying pathophysiology and not only be focused on so-called 'specific' or 'tailored' drug therapy to lower RV afterload. In addition therapeutic efforts should aim to optimise RV preload, and to achieve adequate myocardial perfusion, and cardiac output. Early recognition of patients at high risk and timely initiation of appropriate therapeutic measures may prevent the development of severe cardiac dysfunction and low cardiac output. In patients not responding adequately to pharmacotherapy, (1) novel surgical and interventional techniques, temporary mechanical circulatory support with extracorporeal membrane oxygenation, (2) pumpless lung assist devices (3) and/or lung or heart-lung transplantation should be timely considered. The invasive therapeutic measures can be applied in a bridge-to-recovery or bridge-to-lung transplant strategy. This consensus statement focuses on the management of acute severe PH in the paediatric intensive care unit and provides an according treatment algorithm for clinical practice.

Topics: Acute Disease; Administration, Inhalation; Administration, Intravenous; Adolescent; Cardiac Output; Child; Consensus; Critical Care; Disease Management; Disease Progression; Endothelium-Dependent Relaxing Factors; Extracorporeal Membrane Oxygenation; Heart-Lung Transplantation; Humans; Hypertension, Pulmonary; Iloprost; Intensive Care Units, Pediatric; Lung Transplantation; Nitric Oxide; Oxygen Inhalation Therapy; Phosphodiesterase 5 Inhibitors; Prostaglandins; Sildenafil Citrate; Vasodilator Agents; Ventricular Dysfunction, Right

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

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

Iloprost, a prostacyclin analogue with a prolonged plasma half-life has beneficial effects in chronic pulmonary hypertension, whereas the effects in acute lung injury (ALI) are unknown. The present study was performed to evaluate the cardiopulmonary effects of iloprost in experimental ALI. ALI was induced in 18 pigs by repeated lung lavage. Animals were randomised to controls, i.v. or inhaled iloprost for 15 min. Haemodynamics, gas exchange and ventilation-perfusion distribution were measured at the end of iloprost application and after 1 and 2 h. As a short-term effect, both i.v. and inhaled iloprost significantly decreased pulmonary artery pressure without major effects on gas exchange or systemic haemodynamics. After 1 and 2 h, a reduction of pulmonary hypertension was no longer present. As a long-term effect, inhaled, but not i.v., iloprost decreased pulmonary shunt and significantly improved gas exchange after 1 and 2 h. In conclusion, the single application of iloprost revealed short-term pulmonary vasodilation without other major cardiopulmonary effects. However, inhaled iloprost improved gas exchange due to a decrease of pulmonary shunt as a long-term effect, possibly as a result of a reduction of lung oedema formation.

Topics: Acute Disease; Administration, Inhalation; Analysis of Variance; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hemodynamics; Hypertension, Pulmonary; Iloprost; Injections, Intravenous; Lung Diseases; Lung Injury; Probability; Pulmonary Circulation; Pulmonary Gas Exchange; Random Allocation; Swine

The local ischemia-reperfusion (I/R) process gains a systemic nature and affects distal organs. The remote effects of I/R are most frequently observed in the lungs and pulmonary damage may vary from acute lung injury with mild dysfunction to severe respiratory failure or the acute respiratory distress syndrome. In this hind limb I/R induced experimental lung injury model two groups of rats as IR and ILO were determined. Both groups underwent 60 min of ischemia and 120 min of reperfusion. While ILO group received iloprost in saline, IR group received only saline before reperfusion period intravenously. Serum myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels and total antioxidant capacity (TAC) and lung tissue MPO activity, MDA levels and Na+-K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The MPO activities in serum and lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01). The MDA levels in lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01), but the decreases were not significant in serum MDA levels (P=0.052). Serum TAC and lung tissue Na+-K+ ATPase activity levels were found to be increased in ILO group compared to IR group (P < or = 0.01). Lung histology showed marked improvement by iloprost compared to the IR group in this study. Iloprost has been found to be effective in attenuating ischemia reperfusion-induced remote organ damage, in this case, lung injury, in rats.

Topics: Acute Disease; Adenosine Triphosphatases; Animals; Antioxidants; Cation Transport Proteins; Hindlimb; Iloprost; Male; Malondialdehyde; Neutrophil Infiltration; Peroxidase; Pulmonary Alveoli; Pulmonary Edema; Rats; Rats, Wistar; Reperfusion Injury; Respiratory Insufficiency; Sodium-Potassium-Exchanging ATPase; Vasodilator Agents

The effects of stable prostacyclin analogue iloprost on the trypsinogen activation, labilization of lysosomal membranes, lipolytic enzymes activities, histopathological and ultrastructural changes in the pancreas of rats with severe, taurocholate acute pancreatitis (AP), preceded for 6 h by acute ethanol intake have been investigated. Iloprost (1 microg/kg b.w., i.p.) was applied every 6 hours after inducing of taurocholate AP. The antecedent intragastric 40% ethanol intake (5 g/kg b.w.) increased an index of trypsinogen activation in AP lasting 18 h. Treatment with iloprost prevented this increase in the rats with AP given earlier alcohol, and limited the labilization of lysosomal membranes in nonalcoholized rats with AP. Phospholipase A2 and lipase activities were reduced by iloprost only in the rats not given ethanol. The additional damaging effect of acute ethanol abuse prior to AP could be dependent on augmented activation of trypsinogen. The protective effect of iloprost in AP seems to be dependent on the attenuation of trypsinogen activation, decrease of total potential trypsin and the decrease of lysosomal membranes labilization. Its protective effect could be limited in taurocholate acute pancreatitis preceded by acute ethanol intake as evidenced by the differences in the cathepsin B, phospholipase A2 and lipase activities and by histopathological and ultrastructural examination.

Topics: Acute Disease; Animals; Disease Models, Animal; Ethanol; Iloprost; Intracellular Membranes; Lipase; Lysosomes; Male; Pancreas; Pancreatitis; Phospholipases A; Phospholipases A2; Rats; Rats, Wistar; Taurocholic Acid; Trypsinogen

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

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

Prostacyclin (PGI2) and its stable analogue iloprost (I) exert beneficial effect in acute pancreatitis (AP). The aim of the study was to evaluate the role of iloprost in pancreas regeneration after AP in rats.. AP was induced in male Wistar rats by s.c. injections of caerulein 12 micrograms/kg t.i.d. for 2 days. Rats were divided into four groups: control + saline (C); control + iloprost (C/I); AP + saline (AP); AP + I (AP/I). Rats were treated for 7 or 14 days. I (Schering AG) was given at the dose I microgram/kg b.w., i.p., t.i.d. After the rats were killed, the pancreata were weighed and their protein, DNA, RNA, chymotrypsin, alpha-amylase contents were evaluated. Light microscopic examination of representative pieces of pancreas was performed.. Acute pancreatitis resulted in pancreas destruction observed even 7 days after the onset of the disease. The significant decrease of pancreatic weight, RNA and chymotrypsin contents were observed in AP rats when compared to C. The improvement of pancreatic histology and significant increase of DNA content were found in I treated (during 7 days) AP rats in comparison to untreated AP group. Two weeks after pancreatitis induction the pancreas regeneration occurred in both pancreatitis groups and it was connected with pancreas hypertrophy. Treatment with I resulted in slight not significant increase of some of cellular hypertrophy indices when compared to AP untreated animals. Healthy rats injected with I during 7 days showed significant elevation of DNA content in comparison to C. When treatment with I was prolonged up to 14 days such hyperplastic effect was not observed. Our results suggest, that treatment with iloprost exerts temporary hyperplastic influence on the pancreas of healthy rats and pancreas regenerating after caerulein-induced pancreatitis.

Topics: Acute Disease; Animals; Ceruletide; Iloprost; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regeneration

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

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

Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5% sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100% to 50%. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14,950, 0.2 mg/kg body weight) or dazmegrel (UK 38,485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P less than 0.05); with dazmegrel and iloprost it was 10% (P less than 0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis.

Topics: Acute Disease; Animals; Epoprostenol; Flunarizine; Iloprost; Imidazoles; Male; Necrosis; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Thromboxane A2; Vasodilator Agents

The ability of plasma to support prostacyclin like activity from human umbilical arterial rings was studied in 17 patients with Henoch-Schönlein purpura and 17 controls matched for age and sex. Plasma from 13 of the 17 patients showed a diminished or absent ability to support prostacyclin like activity in vitro. Six patients whose plasma had a low or absent ability to support prostacyclin like activity showed evidence of inhibitory activity. Plasma from three of these patients also failed to preserve the effect of a stable prostacyclin like analogue (ZK36-374). The plasma concentration of prostacyclin metabolite and the serum concentration of thromboxane A2 metabolite, thromboxane B2, were measured simultaneously. The concentration of plasma prostacyclin metabolite in 10 of the 14 patients was decreased, and a positive correlation was found between the plasma prostacyclin metabolite values and the ability of the plasma to support prostacyclin like activity. There was no significant difference in the serum thromboxane A2 metabolite concentrations between the patients and controls. These data suggest that abnormalities of vascular prostaglandin metabolism are involved in the pathophysiology of Henoch-Schönlein purpura.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Epoprostenol; Humans; IgA Vasculitis; Iloprost; Muscle, Smooth, Vascular; Thromboxane B2