iloprost and Necrosis

Topics: Adult; Age Distribution; Calcium Channel Blockers; Female; Humans; Iloprost; Losartan; Male; Middle Aged; Necrosis; Prognosis; Raynaud Disease; Risk Factors; Sex Distribution; Smoking; Vasodilator Agents; Verapamil

There are three distinct syndromes of heparin-induced thrombocytopenia: an acute reversible from seen immediately after intravenous bolus injection, a delayed-onset antibody-mediated form seen several days after the initiation of therapy, and an intermediate type characterized by mild thrombocytopenia developing just a few days after starting therapy. Delayed-onset heparin-induced thrombocytopenia, clinically the most important form, results from the formation of heparin-dependent antibodies that are directed against the platelet membrane. In the presence of heparin, these antibodies may induce in vitro or in vivo platelet aggregation. Consequently, the course may be complicated by arterial thromboses. Treatment of this syndrome includes the prompt cessation of heparin. Since continued or future anticoagulation is usually necessary, alternative means of anticoagulation have been explored. Oral anticoagulation is often started but requires several days to take effect. Other options include low-molecular-weight heparins, antiplatelet agents, prostacyclin analogues, and low-molecular-weight dextran. In vitro laboratory tests may be helpful in guiding alternative therapy in some, but not all cases. Unfortunately, none of these agents have proved to be uniformly effective and additional agents and clinical investigation are needed before a definitive option becomes available.

Topics: Aspirin; Cardiopulmonary Bypass; Chondroitin Sulfates; Dermatan Sulfate; Epoprostenol; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Iloprost; Necrosis; Platelet Aggregation Inhibitors; Skin; Skin Diseases; Thrombocytopenia; Thrombosis

Patients with systemic sclerosis (SSc) develop often acral ulcers which are resistant to therapy and may result in gangrene and amputation. We investigated the effects of iloprost infusion on the acral ulcers and necrosis in patients with five patients with SSc and one with mixed connective tissue disease who had been previously treated with various modalities without improvement. All patients had Raynaud phenomenon, acral ulcers and necrosis. Iloprost 25 microg per day was administered intravenously daily over six hours for ten consecutive days. Eight weeks later all patients were treated with a second iloprost therapy cycle for five days. Two patients with severe ulceration received a third cycle until remission occurred. In all cases acral ulcers healed completely and no patient relapsed during an observation period of 6 months.

Topics: Adult; Aged; Drug Administration Schedule; Drug Resistance; Female; Fingers; Humans; Iloprost; Infusions, Intravenous; Middle Aged; Necrosis; Scleroderma, Systemic; Secondary Prevention; Skin Ulcer; Treatment Outcome

Topics: Adult; Alprostadil; Connective Tissue Diseases; Female; Fingers; Humans; Iloprost; Male; Middle Aged; Necrosis; Raynaud Disease; Vasodilator Agents

Digital ulcers (DUs) occur in up to 50% of patients with Systemic Sclerosis (SSc). DUs are painful, recurring and lead to functional disability. Management of DUs includes pharmacologic and local therapy, the healing process is slow and the ulcer can become infected or evolve to gangrene. Autologous fat grafting (AFG) is a technique used to promote tissues repair. We used AFG to treat DUs refractory to conventional treatment to enhance healing process.. We treated 9 SSc patients for a total of 15 ulcers. All 9 patients were treated with iv Iloprost. The purified fat tissue was injected at the border of larger ulcers or at the finger base of smaller DUs. The AFG was performed from 2 to 8 months since the ulcer onset.. Complete healing occured in 10 DUs and size reduction ≥50% in 2, within 8-12 weeks. In all but 2 patients the pain improved allowing a reduction of analgesics. In the majority of the cases AFG was able to hasten ulcer healing and to reduce pain and the need of pharmacological therapy. The lack of efficacy on healing and pain reduction was observed when the ulcers were long-lasting, located on legs and with concurrent atherosclerotic macroangiopathy.. Surgical resective treatment for finger ulcers in patients affected by SSc is fraught with morbidity and long prolonged recovery. This study introduces a novel minimally invasive approach. The procedure is safe and effective, with short recovery time and local deficient vascularization improvement.

Topics: Adipose Tissue; Adult; Aged; Amputation, Surgical; Combined Modality Therapy; Female; Fingers; Hand Deformities, Acquired; Humans; Iloprost; Infusions, Intravenous; Italy; Male; Middle Aged; Necrosis; Plastic Surgery Procedures; Scleroderma, Systemic; Skin Ulcer; Treatment Outcome; Wound Healing

Topics: Amputation, Surgical; Antibodies, Antinuclear; Female; Fingers; Humans; Iloprost; Middle Aged; Necrosis; Platelet Aggregation Inhibitors; Prednisolone; Raynaud Disease; Severity of Illness Index; Syndrome; Toes; Treatment Failure

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Fingers; Hodgkin Disease; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Multimodal Imaging; Necrosis; Positron-Emission Tomography; Raynaud Disease; Remission Induction; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents; Vinblastine

Topics: Angioplasty, Balloon, Coronary; Embolism, Cholesterol; Humans; Hyperbaric Oxygenation; Iloprost; Male; Middle Aged; Myocardial Infarction; Necrosis; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Stents; Tomography, X-Ray Computed

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

A retrospective study of drug abuse patients who developed arterial and venous complications in the upper extremity during 2002-2006 was performed. Twenty-two patients were admitted to hospital on 24 occasions over this period for treatment by our hand clinic. The drug most frequently causing complications was midazolam. The predominant clinical findings were increasing pain and loss of sensitivity in the hand, followed by oedema, cyanosis and marbling of the skin. Treatments included brachial block anaesthesia, low molecular weight heparin, embolectomy and fasciotomies. Despite these measures, amputations, mainly of the fingertips, were necessary in 15 patients. Complications in the upper extremity after self-injection by drug addicts are increasing; information and preventive procedures to minimize these complications are important and demanding tasks for health care bodies.

Topics: Adult; Amputation, Surgical; Angiography; Anti-Bacterial Agents; Anticoagulants; Compartment Syndromes; Cyanosis; Dermatologic Surgical Procedures; Edema; Embolectomy; Fasciotomy; Female; Fibrinolytic Agents; Heparin; Hospitalization; Humans; Iloprost; Male; Necrosis; Nerve Block; Retrospective Studies; Sensation Disorders; Skin; Skin Diseases; Substance Abuse, Intravenous; Surgical Flaps; Tissue Plasminogen Activator; Upper Extremity; Vasodilation; Vasodilator Agents

The effects of iloprost on ischemia-reperfusion injury have been studied on the skeletal, muscle, liver, myocardium, kidney, and spinal cord. However, no sufficient data exist about effects of levosimendan on renal ischemia-reperfusion injury. The purpose of this experimental study was to investigate and compare effectiveness of levosimendan and iloprost on renal injury induced by ischemia and reperfusion. Fifty rabbits were divided into five groups. Levosimendan was continuously infused starting half an hour before the cross-clamp. Cross-clamp time was one hour. After one hour ischemia, levosimendan was continued for 4 h in Group A whereas Group B took iloprost in the same protocol. Group C was the control group which did not receive any medication. Group D was sham group and Group E was medicated both iloprost and levosimendan. Renal tissues were histologically and biochemically evaluated. The histological scores were obtained according to presence of tubular necrosis and atrophy, regenerative atypia, hydropic degeneration (Group A vs. Group C<0.001, Group B vs. Group C<0.001, Group D vs. Group C<0.01, Group E vs. Group C<0.001). Mean malondialdehyde levels were 114+/-12 nmol/g tissue; in Group A 121+/-13 nmol/g tissue, in Group B 134+/-13 nmol/g tissue, in Group E 130+/-11 nmol/g tissue, in Group D 134+/-11 nmol/g tissue (Group A vs. Group B; P=0.003, Group B vs. Group D; P=0.132, Group A vs. Group E; P=0.132). Malondialdehyde levels and histologic scores of all of the groups were significantly different from the control group. Iloprost and pentoxyfillin reduced renal ischemia-reperfusion injury in rabbit model. There was no significant difference between these two medications.

Topics: Animals; Atrophy; Disease Models, Animal; Female; Hydrazones; Iloprost; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Malondialdehyde; Necrosis; Protective Agents; Pyridazines; Rabbits; Reperfusion Injury; Simendan

Topics: Adult; Bosentan; Endothelin Receptor Antagonists; Female; Fingers; Humans; Iloprost; Necrosis; Platelet Aggregation Inhibitors; Recurrence; Scleroderma, Systemic; Sulfonamides; 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

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 effects of an intravenous infusion of L-arginine as a physiological precursor of endothelium-derived relaxing factor/nitric oxide (EDRF/NO), iloprost (a stable prostacyclin (PGI2) analogue), and L-arginine combined with iloprost on skin viability were studied in 9 x 3 cm random pattern skin flaps in rats. Intravenous infusion of all drugs was started at the beginning of the operation and continued for 60 minutes. At the end of infusion period the depth of fluorescein dye penetration in the skin flap was assessed visually from photographic records, and the flap survival area was measured by the grid method at the seventh postoperative day. There was a significant reduction in distal necrosis of random skin flaps after intravenous infusion of L-arginine, iloprost, and L-arginine combined with iloprost (p < 0.01). Possible mechanisms that may be responsible for impairment of endothelium-dependent vasodilation and vasospasm in the microvasculature of random skin flap and their prevention with L-arginine and iloprost include restoration of the depleted stores of NO which in turn causes vasodilatation and has an antithrombotic effect.

Topics: Animals; Arginine; Drug Therapy, Combination; Graft Survival; Iloprost; Male; Microcirculation; Necrosis; Nitric Oxide; Rats; Rats, Wistar; Surgical Flaps; Vasodilator Agents

In order to elucidate the relation between tissue eicosanoids and liver injury due to bile duct obstruction, we have examined the effects of iloprost, a stable analogue of prostaglandin I2 (PGI2), and UK 38485 (UK), an inhibitor of thromboxane synthetase, on prostaglandin E2 (PGE2) and leukotriene C4(LTC4) in guinea pig liver. 56 male guinea pigs were divided into the following groups: (i) sham operations (SHAM), (ii) bile duct ligated (BDL) group, (iii) guinea pigs given UK (5 micrograms/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation), and (iv) guinea pigs treated with iloprost (ILO) (2 micrograms/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation). Liver damage was assessed by blind quantitation of liver cell necrosis. Bile duct ligation caused an increase in tissue PGE2-like activity and a decrease LTC4-like activity. But the most pronounced elevation of PGE2-like activity was observed in ILO treated group. The LTC4-like activity level improved significantly in the UK-treated BDL group compared with the BDL only and ILO treated animals. Also, UK was found to be beneficial in preventing the liver cell necrosis due to cholestasis. It is concluded that the ratio of PGE2/LTC4 in liver is a valuable marker for cholestatic injury.

Topics: Animals; Bile Ducts; Biomarkers; Cholestasis, Extrahepatic; Dinoprostone; Guinea Pigs; Iloprost; Imidazoles; Leukotriene C4; Ligation; Liver; Male; Necrosis; Thromboxane-A Synthase

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

Iloprost has been shown to minimize skeletal muscle necrosis when administered before the onset of ischemia in animal experiments, possibly by preventing neutrophil activation. Since patients with acute limb ischemia are seen after the process has begun, we investigated whether iloprost can be protective when given only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a standard isolated gracilis muscle preparation. In six control animals (group I) the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle ischemia and throughout the experiment (6 hours of ischemia and 1 hour of reperfusion). In addition to the continuous infusion, they received 0.45 microgram/kg intravenous boluses of iloprost 10 minutes before the induction of ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a similar ischemic interval, but were given a bolus of iloprost of 0.45 microgram/kg at end ischemia followed by continuous infusion of 0.45 microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at baseline and after 1 hour of reperfusion in all groups. Additional biopsies were obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase activity, a marker of neutrophil activation, was measured in all muscle biopsies. At the end of reperfusion, the gracilis muscle was harvested in all animals and weighed. Muscle necrosis was estimated by serial transection, nitroblue tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Dogs; Iloprost; Infusions, Intravenous; Injections, Intravenous; Muscles; Necrosis; Neutrophils; Peroxidase; Reperfusion Injury; Time Factors

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

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

Topics: Animals; Cardiovascular Agents; Coronary Disease; Drug Evaluation, Preclinical; Epoprostenol; Heart; Iloprost; Myocardial Infarction; Myocardium; Necrosis; Rabbits; Radionuclide Imaging; Technetium Tc 99m Aggregated Albumin

It was investigated whether the prostacyclin derivative Iloprost (Schering, Berlin) protects rat hepatocytes against lethal damage induced by carbon tetrachloride (CCl4) and bromobenzene (BB). Iloprost was tested in whole animal experiments (intoxication with 2 ml CCl4/kg) and with primary hepatocyte cultures (intoxication with 1.6 mM BB). Cell damage was estimated by light microscopic examination of hepatocellular morphology and by the release of hepatocellular enzymes (glutamic-pyruvic transaminase, GPT; glutamic-oxalacetic transaminase, GOT; lactic dehydrogenase, LDH) into the blood or culture medium. In both experimental set-ups, Iloprost (0.1 micrograms/kg/min in whole animal experiments and 10(-9)-10(-12) M in primary hepatocyte cultures) largely preserved normal hepatocellular morphology after intoxication. Furthermore, the toxin-induced release of hepatocellular enzymes into the blood (GOT, GPT) or into the culture medium (LDH) was reduced by 50%-70% in the presence of Iloprost. It is concluded that the prostacyclin derivative Iloprost possesses cytoprotective activity on rat hepatocytes against lethal injury by CCl4 or BB.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Bromobenzenes; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Epoprostenol; Iloprost; L-Lactate Dehydrogenase; Liver Diseases; Male; Necrosis; Rats