iloprost and Heart-Diseases

Pilot study to compare the effect of inhaled nitric oxide (iNO) and aerosolized iloprost in preventing perioperative pulmonary hypertensive crises (PHTCs).. Guidelines recommend the use of iNO to treat PHTCs, but treatment with iNO is not an ideal vasodilator. Aerosolized iloprost may be a possible alternative to iNO in this setting.. Investigator-initiated, open-label, randomized clinical trial in 15 infants (age range 77-257 days) with left-to-right shunt (11 out of 15 with additional trisomy 21), and pulmonary hypertension (i.e. mean pulmonary artery pressure [PAP] >25 mmHg) after weaning from cardiopulmonary bypass. Patients were randomized to treatment with iNO at 10 ppm or aerosolized iloprost at 0.5 µg/kg (every 2 h). The observation period was 72 h after weaning from cardiopulmonary bypass. The primary endpoint was the occurrence of PHTCs; the secondary endpoints were mean PAP, duration of mechanical ventilation, safety of administration, and in-hospital mortality.. Seven patients received iNO and eight patients received iloprost. During the observation period, 13 of the 15 patients had at least one major or minor PHTC. There was no difference between the groups with regard to the frequency of PHTCs, mean PAP and duration of mechanical ventilation (p > 0.05).. In this pilot study, aerosolized iloprost had a favorable safety profile. Larger trials are needed to compare its efficacy to iNO for the treatment of perioperative pulmonary hypertension. However, neither treatment alone abolished the occurrence of PHTCs.

Topics: Administration, Inhalation; Bronchodilator Agents; Cardiopulmonary Bypass; Heart Diseases; Humans; Hypertension, Pulmonary; Iloprost; Infant; Nitric Oxide; Pilot Projects; Postoperative Complications; Treatment Outcome; Vasodilator Agents

Some biomarkers play important roles in the endothelial dysfunction of patients with pulmonary arterial hypertension (PAH), including nitric oxide (NO), endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), galectin-3 (Gal-3), B-type natriuretic peptide (BNP), and uric acid (UA). However, studies on these biomarkers in pulmonary artery blood in congenital heart disease-PAH (CHD-PAH) and the effect of iloprost on the regulation of biomarkers are lacking. This study investigated potential CHD-PAH biomarkers and their association with the severity of disease. The effect of iloprost on the regulation of these biomarkers was also studied. A total of 31 patients with CHD-PAH were enrolled. Seven with positive effects of iloprost (the average reduction in mPAP 11.13±1.73 mm Hg) and 19 with negative effects of iloprost (the average reduction in mPAP 4.21±4.87 mm Hg; iloprost positive group [IPG] vs iloprost negative group [ING], P<.01) and five age-matched controls were studied. The pulmonary artery blood sample was collected before and after inhaling iloprost, and the plasma concentrations of Gal-3, ADMA, ET-1, and NO were measured. A significant positive linear relationship was observed between mPAP and plasma ET-1, BNP, ADMA, and UA levels in all patients with CHD-PAH. ET-1, ADMA, BNP, and UA levels had a significant linear relationship with mean pulmonary arterial pressure, which could be used to predict the severity of CHD-PAH. ET-1 might be a potential biomarker to pre-evaluate the effect of iloprost on CHD-PAH. Iloprost could affect the expression of Gal-3 and, therefore, the process of fibrosis could be influenced by iloprost.

Topics: Biomarkers; Female; Heart Diseases; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged

During cardiac operations, weaning from cardiopulmonary bypass (CPB) may prove challenging as a result of superimposed acute right ventricular dysfunction in the setting of elevated pulmonary vascular resistance (PVR). The aim of this study was to retrospectively evaluate the effect of inhaled milrinone versus inhaled iloprost in patients with persistent pulmonary hypertension following discontinuation of CPB. Eighteen patients with elevated PVR post-bypass were administered inhaled milrinone at a cumulative dose of 50 μg kg

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Arterial Pressure; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Diseases; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Milrinone; Postoperative Complications; Retrospective Studies; Treatment Outcome; Vascular Resistance; Vasodilator Agents

Pulmonary hypertension (PH) is an independent risk factor for increased mortality in patients undergoing heart surgery. Existing chronic PH may be exacerbated by acute post-bypass PH, and this can lead to acute right ventricular failure. The prevention and treatment of right ventricular failure in cardiac surgery is based on three principles: optimize right ventricular preload, improve right ventricular contractility, minimize right ventricular afterload. The last of these may involve specific measures such as the inhalation of nitric oxide (NO) or of the stable prostacyclin analogue iloprost. The advantage of these inhalable substances is their pulmonary selectivity, and the subsequent reduction in systemic side effects. In order to avoid disastrous results in high-risk cardiac surgical patients, intra- and post-operative monitoring with pressure lines, a qualified team that pays attention to details, and an aggressive and early treatment in the operating room with inhaled iloprost and/or NO is necessary. The philosophy of 'wait and see' should be abandoned in favour of 'be suspicious and act early'. In a prospective randomized trial, the efficacies of inhaled iloprost and of inhaled NO in the therapy of PH immediately following weaning from cardiopulmonary bypass in cardiac surgical patients were compared. Iloprost proved to be significantly more effective with respect to mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output than inhaled NO.

Topics: Adult; Cardiac Surgical Procedures; Heart Diseases; Humans; Hypertension, Pulmonary; Iloprost; Nitric Oxide; Perioperative Care; Postoperative Complications; Risk Factors; Vasodilator Agents

Nebulised iloprost is established therapy of severe pulmonary hypertension; however, the effects on the bronchoalveolar compartment have not been investigated so far. We studied the short- and long-term effects of nebulised iloprost on pulmonary function tests and gas exchange in 63 patients with severe pulmonary hypertension (idiopathic n=17, chronic thromboembolism n=15, connective tissue disease n=12, congenital heart disease n=11, respiratory diseases n=8). Patients received iloprost in increasing dose up to 140 micro g iloprost/24h via an ultrasonic nebuliser. Short-term effects were assessed before and after every nebulisation: peak expiration flow decreased in mean by 1.9% (423+/-98 to 415+/-98) and percutaneous oxygen saturation increased in mean by 0.7% (90+/-6 to 91+/-5) post-nebulisation. There were no significant differences concerning underlying diagnosis or dose of nebulised iloprost. Within 3 months, 9 patients stopped treatment due to non-compliance with frequent nebulisations (n=3), or severe side effects (n=4); 2 patients with additional obstructive lung disease developed bronchoconstriction. Long-term effects were assessed by pulmonary function tests and gas exchange parameters at baseline and after 3 months treatment. There were no significant differences after 3 months therapy neither in FEV(1), FVC, TLC, residual volume nor in diffusions capacity, SO(2) at rest and during 6 min walking test, also in respect of the underlying diseases. However, there was a significant increase in 6 min walking distance (6 MWD) after 3 months (246+/-113 to 294+/-115 m, P<0.05). In conclusion, treatment with nebulised iloprost leads to functional improvement in severe pulmonary hypertension without systematic adverse short- and long-term effects on pulmonary function test or gas exchange. Patients with additional obstructive lung disease might develop bronchoconstriction. Severe side effects leading to discontinuation of treatment occurred in 9% of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Connective Tissue Diseases; Female; Forced Expiratory Flow Rates; Heart Diseases; Humans; Hypertension, Pulmonary; Iloprost; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pulmonary Embolism; Respiratory Function Tests; Sulfur Dioxide; Treatment Outcome; Vasodilator Agents; Vital Capacity

To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of COX-2 (COX-2-/-). After treatment with Dox, COX-2-/- mice had increased cardiac dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice. The expression of the death-associated protein kinase-related apoptosis-inducing protein kinase-2 was also increased in Dox-treated COX-2-/- animals. The altered gene expression, cardiac injury, and dysfunction after Dox treatment in COX-2-/- mice was attenuated by a stable prostacyclin analog, iloprost. Wild-type mice treated with Dox developed cardiac fibrosis that was absent in COX-2-/- mice and unaffected by iloprost. These results suggest that genetic disruption of COX-2 increases the cardiac dysfunction after treatment with Dox by an increase in cardiac cell apoptosis. This Dox-induced cardiotoxicity in COX-2-/- mice was attenuated by a prostacyclin analog, suggesting a protective role for prostaglandins in this setting.

Topics: Animals; Antineoplastic Agents; Apoptosis; bcl-X Protein; Cyclooxygenase 2; Doxorubicin; Echocardiography; Gene Expression Regulation, Enzymologic; Heart Diseases; Hemodynamics; Iloprost; Male; Mice; Mice, Knockout; Myocytes, Cardiac; Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vasodilator Agents

Patients with preoperatively diagnosed type II heparin-induced thrombocytopenia (HIT) scheduled for cardiopulmonary bypass (CPB) present a challenge in their intraoperative anticoagulation management because re-exposure to heparin may result in profound thrombocytopenia, intravascular thromboses, bleeding, and even death. Iloprost, a prostacyclin analogue that reversibly inhibits platelet aggregation, has been suggested as a management approach in such cases. The purpose of this study was to assess and confirm the efficacy of a perioperative intravenous iloprost infusion in preventing thromboembolic complications in patients with type II HIT undergoing cardiac surgery and requiring the use of heparin and CPB.. During a one-and-a-half-year period, 22 patients with type II HIT presented at the Cardiac Surgery Service of the Onassis Cardiac Center in Athens. In these patients, platelet aggregation test results were found strongly positive at heparin serum concentrations corresponding to those achieved during CPB. Iloprost was used in a preoperatively, in vitro-determined, patient-specific concentration that was assessed and modified perioperatively depending on its in vivo effect on platelet aggregation as opposed to the conventional constant rate.. In the 22 patients, the preoperatively determined concentration of iloprost seemed to correlate well with the in vivo interruption of platelet aggregation, as tested by a perioperative heparin-induced platelet aggregation (HIPA) assay, and in only 3 cases (14%) was the rate of iloprost infusion increased. The patients' platelet counts, which were evaluated peri- and postoperatively, were preserved with no statistically significant fluctuations. Postoperative bleeding was within normal limits and no thrombotic episodes or other complications were reported.. Although a number of alternative anticoagulation methods, such as the use of another anticoagulant (danaparoid sodium and recombinant hirudin) or the preoperative use of a defibrinogenating agent (ancorod), have been suggested for patients with type II HIT requiring anticoagulation during CPB, the use of heparin associated with a potent platelet inhibitor such as the prostacyclin analog iloprost is, as this study confirmed, the only to-date safe and effective choice.

Topics: Aged; Anticoagulants; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Female; Heart Diseases; Heparin; Humans; Iloprost; Male; Middle Aged; Platelet Aggregation Inhibitors; Preoperative Care; Retrospective Studies; Thrombocytopenia

Topics: Antibodies, Antiphospholipid; Diagnosis, Differential; Female; Heart Atria; Heart Diseases; Heart Neoplasms; Heparin; Humans; Iloprost; Middle Aged; Myxoma; Thrombocytopenia; Thrombosis

The effect of iloprost was investigated in an experimental model of cardiac damage in rats after isoprenaline (isoproterenol) treatment. Iloprost was administered by continuous subcutaneous infusion at a dose of 0.44 micrograms/kg body weight (b.w.)/min over a total period of 9 days. On day 8, 5 mg isoprenaline/kg b.w. was applied subcutaneously to induce the cardiac damage. The determinations of creatine kinase (CK, EC 2.7.3.2) and CK isoenzymes, lactate dehydrogenase (LDH, EC 1.1.1.27) and LDH isoenzymes as well as a-hydroxybutyrate dehydrogenase (a-HBDH, no EC) were performed 2, 6 and 24 h after isoprenaline application. Immediately after the last blood sampling, the animals were sacrificed and the hearts were examined histologically. Iloprost-pretreated animals showed a reduction in the rise in heart-specific isoenzymes CK-MB and LDH1-3 in the serum after isoprenaline application. A decrease in isoenzymes CK-BB and LDH4-5 in the serum was also observed in iloprost-pretreated rats. However, no difference could be detected histologically in the extent of myocardial necrosis between animals treated with isoprenaline alone or in combination with iloprost. These results suggest a biochemical cardioprotective effect of iloprost in this rat model after isoprenaline application and the lack of correlation with histological findings is discussed.

Topics: Animals; Creatine Kinase; Epoprostenol; Heart Diseases; Iloprost; Isoenzymes; Isoproterenol; L-Lactate Dehydrogenase; Male; Rats; Rats, Inbred Strains; Time Factors

Topics: Aged; Drug Evaluation; Epoprostenol; Female; Heart Diseases; Heparin; Humans; Iloprost; Male; Middle Aged; Thrombocytopenia