iloprost and Heart-Failure

Pulmonary hypertension (PH), an often unrelenting disease that carries with it significant morbidity and mortality, affects not only the pulmonary vasculature but, in turn, the right ventricle as well. The survival of patients with PH is closely related to the right ventricular function. Therefore, having an understanding of how to manage right ventricular failure (RVF) and acute pulmonary hypertensive crises is imperative for clinicians who encounter these patients. This review addresses the management of these patients in detail, addressing: (a) the pathophysiology of RVF, (b) intensive care monitoring of these patients in the intensive care unit, (c) imaging of the right ventricle, (d) intubation and mechanical ventilation, (e) inotrope and vasopressor selection, (f) pulmonary vasodilator use, (g) interventional and surgical procedures for the acutely failing right ventricle, and (h) mechanical support for RVF.

Topics: Biomarkers; Capnography; Central Venous Pressure; Critical Care; Echocardiography; Epinephrine; Epoprostenol; Extracorporeal Membrane Oxygenation; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Iloprost; Intensive Care Units; Milrinone; Nitric Oxide; Radiography, Thoracic; Respiration, Artificial; Spectroscopy, Near-Infrared; Vasodilator Agents; Vasopressins; Ventricular Dysfunction, Right; Ventricular Function, Right

Pulmonary arterial hypertension (PAH) is a progressive disease marked by vasoconstriction and vascular remodeling within pulmonary arteries leading to right heart failure and death. Significant advances in understanding the pathobiology of the disease have identified three key pathways involved in progression of this disease, which are the endothelin pathway, the prostacyclin pathway, and the nitric oxide/cyclic guanosine monophosphate pathway. Echocardiogram is the best screening tool to obtain an estimation of the pulmonary artery systolic pressure but right heart catheterization remains the standard by which the diagnosis is made. There are currently six FDA approved therapies for PAH. The mechanistic rationale, evidence behind their use and side effect considerations in utilizing these therapies in PAH patients will be the focus of this review.

Topics: Antihypertensive Agents; Bosentan; Cardiac Catheterization; Disease Progression; Drug Therapy, Combination; Endothelin Receptor Antagonists; Endothelium, Vascular; Epoprostenol; Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Isoxazoles; Phosphodiesterase Inhibitors; Piperazines; Platelet Aggregation Inhibitors; Prognosis; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Thiophenes; Vasoconstriction

Type Sphosphodiesterase inhibitors (FDEI-5) used to be applied as the main drugs for treatment of erectile dysfunction. At present, this pharmacological group is being studied intensively in various fields of clinical medicine, such as pulmonology, cardiology, gastroenterology, gynecology etc. Part II of this system literature review is dedicated to analysis of the results of such application. In many randomized and non-randomized controlled studies sildenafil decreased pulmonary arterial pressure (independently of etiology) and pulmonary vascular resistance; it could be successfully combined with nitric oxide, illoprost, or epoprostenolol. Clinical studies have also demonstrated an increase in physical load tolerance, optimization of PAH studies according to NYHA functional classes, and good tolerance to the drug. In the recent years, antiischaemic effects of FDEI-5 and their ability to inhibit apoptosis have been proved It is possible to draw the conclusion that nature created a universal phosphodiesterase mechanism for the interconnection of biochemical processes that provide the vital activity of the cell and organism. The fact that more than 15 controlled studies of clinical application of sildenafil not for treatment of erectile dysfunction have been planned and commenced confirms the importance of further studies of this mechanism. Further analysis of the results will show how universal this mechanism is.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Bronchodilator Agents; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Therapy; Drug Therapy, Combination; Forecasting; Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Myocardial Infarction; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Treatments that improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) have shown no benefits for those with heart failure with preserved ejection fraction (HFpEF). Our study aimed to investigate the effect of inhaled iloprost on myocardial performance during exercise in HFpEF.. The study participants were enrolled from the ILO-HOPE trial (NCT03620526), a prospective randomized, double-blind, placebo-controlled study that was designed to investigate the effects of iloprost on cardiovascular hemodynamics during exercise in patients with HFpEF. Subjects were randomized 1:1 to inhalation of iloprost or placebo for 5 min. Two-dimensional transthoracic echocardiography with high temporal resolution was implemented to measure left ventricular (LV) longitudinal strain, LV diastolic function, and RV function both at rest and during supine exercise at 20-W workload.. LV global longitudinal strain (GLS) in response to exercise increased more in the iloprost group (LV GLS, -24.96 ± 1.20 vs -20.75 ± 3.00, P < 0.001). Iloprost also resulted in greater increment of LV GLS during exercise (ΔLV GLS, +6.02 ± 1.39 vs +3.44 ± 0.80, P < 0.001). Moreover, iloprost use was associated with enhancement of LV diastolic function, RV systolic function, and relief of pulmonary hypertension during exercise.. In patients with HFpEF, inhaled iloprost favorably improved myocardial performance during exercise by increasing LV GLS reserve, decreasing LV diastolic filling load, and reducing stress-induced pulmonary hypertension and thereby improving RV systolic function. Larger studies are needed to validate the result and long-term benefits of iloprost in patients with HFpEF.

Topics: Administration, Inhalation; Aged; Double-Blind Method; Echocardiography; Exercise; Female; Heart Failure; Humans; Iloprost; Male; Middle Aged; Prospective Studies; Stroke Volume; Vasodilator Agents

This randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF).. Twenty-one consecutive patients with CHF and CSR (apnea-hypopnea index [AHI] ≥15/h) underwent right heart catheterization with titration of intravenous (IV) glyceryltrinitrate (GTN) to a maximum tolerable dosage and inhalation of iloprost 10 μg/mL after a washout phase. Maximum tolerable dosages of GTN and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with IV or inhaled sodium chloride (NaCl) 0.9 %, respectively.. GTN (6.2 ± 1.5 mg/h) and iloprost significantly lowered \\mean pulmonary artery pressure (20.1 ± 9.0 to 11.6 ± 4.2 mmHg, p < 0.001 and 16.9 ± 7.9 to 14.2 ± 6.4 mmHg, p < 0.01, respectively). Pulmonary capillary wedge pressure was only reduced by GTN (14.0 ± 5.6 to 7.2 ± 3.9 mmHg, p < 0.001), and there was no significant change in the cardiac index. Sleep studies revealed no significant improvement in markers of CSR severity, including AHI, central apnea index, and CSR cycle length following GTN or iloprost treatment. Significant decreases in blood pressure, mean oxygen saturation, and S3 sleep were documented during GTN infusion.. Acute improvement of pulmonary congestion by GTN had no immediate impact on CSR severity. Future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure.. German Clinical Trial Registry-ID:DRKS00000467 ( www.germanctr.de ).

Topics: Administration, Inhalation; Aged; Cardiac Catheterization; Cardiac Output; Cheyne-Stokes Respiration; Cross-Over Studies; Double-Blind Method; Female; Heart Failure; Hemodynamics; Humans; Iloprost; Infusions, Intravenous; Lung; Male; Middle Aged; Nitroglycerin; Polysomnography; Pulmonary Wedge Pressure

Pulmonary hypertension (PH) can lead to right-side heart failure (RHF) and death. There are no therapeutic recommendations for patients experiencing acute RHF in the course of PH. This study aimed to examine the safety and efficacy of inhaled iloprost in patients with precapillary PH and RHF.. Between October 2007 and December 2008, 7 patients with precapillary PH and RHF were enrolled. Per protocol, iloprost was inhaled hourly for a minimum of 12 hours during a 24-hour period. The starting dose of 2.5 μg was increased hourly by 2.5 μg as long as the increases were tolerated. Safety and efficacy were determined by continuous invasive monitoring of systemic and pulmonary hemodynamic parameters. Systemic pressures remained stable during inhalation (66.1 ± 6.9 mm Hg at baseline and 69.1 ± 6.4 mm Hg immediately after inhalation therapy, P = 0.48). Cardiac index increased from 2.4 ± 0.7 L/min/m(2) to 2.9 ± 0.9 L/min/m(2) (P = .008). Pulmonary vascular resistance decreased from 634.6 ± 218.3 dyn·s·cm(-5) to 489.6 ± 173.8 dyn·s·cm(-5) (P = .044), and N-terminal B-type natriuretic peptide levels decreased from 13,591 ± 10,939 pg/mL to 9,944 ± 8,569 pg/mL (P = .051).. Blood pressure-guided hourly inhalation of iloprost may offer a safe and effective strategy for the treatment of PH patients with RHF.

Topics: Administration, Inhalation; Aged; Blood Pressure Determination; Female; Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome; Vasodilator Agents; Ventricular Dysfunction, Right

An elevated pulmonary vascular resistance (PVR) is described as a predictor of postoperative right heart failure and increased mortality in patients undergoing orthotopic heart transplantation. The use of intravenous vasodilators is limited by their systemic effects. We evaluated the pulmonary and systemic hemodynamic effects of inhaled nitric oxide (NO) and inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated PVR.. Fourteen male heart transplant candidates due to dilative or ischemic cardiomyopathia with elevated PVR (> or = 180 dyn s cm(-5)) were included in the study. Increasing concentrations of NO (5, 10 and 30 ppm) and 50 microg aerosolized IP were administered by inhalation. Hemodynamic measurements preceded and followed administration of each agent.. Inhalation of IP, 10, and 30 ppm NO reduced PVR and mean pulmonary artery pressure (MPAP), but did not affect blood pressure or systemic vascular resistance. Comparing the effectiveness of 10 ppm NO and IP, we found a significant higher reduction of MPAP in patients treated with IP. An increase of cardiac index and stroke index could only be shown with IP-inhalation.. Inhaled iloprost induces pulmonary vasodilation which is significantly greater than the effects of 10 and 30 ppm NO. The results of our study show, that inhaled iloprost induces a reliable hemodynamic response in the evaluation of heart transplant candidates. Further advantages of iloprost inhalation are the lack of adverse reactions and toxic side effects and an easier administration. Due to this facts we recommend iloprost as a routine screening drug for vascular reactivity in HTx-candidates. Based on our results it would be of great interest to investigate the role of iloprost in management of postoperative right heart insufficiency following cardiac transplantation.

Topics: Administration, Inhalation; Adult; Aerosols; Dose-Response Relationship, Drug; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nitric Oxide; Oxygen Consumption; Preoperative Care; Pulmonary Artery; Vascular Resistance; Vasodilator Agents

Inhaled aerosolized iloprost, a stable prostacyclin analogue, has been considered a selective pulmonary vasodilator in the management of pulmonary hypertension.. To assess the efficacy of inhaled iloprost in the treatment of life-threatening pulmonary hypertension.. Open, uncontrolled, multicenter study.. Intensive care units and pulmonary hypertension clinics at six university hospitals in Germany.. 19 patients who had progressive right-heart failure despite receiving maximum conventional therapy (12 with primary pulmonary hypertension, 3 with pulmonary hypertension related to collagen vascular disease without lung fibrosis, and 4 with secondary pulmonary hypertension).. Inhaled iloprost, 6 to 12 times daily (50 to 200 microg/d).. Right-heart catheterization and distance walked in 6 minutes at baseline and after 3 months of therapy.. During the first 3 months of therapy, New York Heart Association functional class improved in 8 patients and was unchanged in 7 patients. Four patients died, 3 of right-heart failure and 1 of sepsis. The acute hemodynamic response to inhaled iloprost was predominant pulmonary vasodilatation with little systemic effect at baseline and at 3 months (data available for 12 patients). Hemodynamic variables were improved at 3 months, and the distance walked in 6 minutes improved by 148 m (95% CI, 4.5 to 282 m; P = 0.048). Of the 15 patients who continued to use inhaled iloprost, 8 stopped: Four had lung transplantation, 1 switched to intravenous prostacyclin therapy, and 3 died. Seven patients are still receiving inhaled iloprost (mean +/-SD) duration of therapy, 536 +/- 309 days; mean dosage, 164 +/- 38 microg/d).. Inhaled iloprost may offer a new therapeutic option for improvement of hemodynamics and physical function in patients with life-threatening pulmonary hypertension and progressive right-heart failure that is refractory to conventional therapy.

Topics: Administration, Inhalation; Adult; Aged; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Pulmonary Gas Exchange; Statistics, Nonparametric; Treatment Outcome; Vasodilator Agents

Pulmonary hypertension is a life-threatening complication of lung fibrosis. Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch. We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in randomized order and, in addition, tested for effects of oxygen and systemic calcium antagonists (CAAs) in eight patients with lung fibrosis and pulmonary hypertension. Aerosolized prostaglandin (PG)I(2) caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 +/- 4.2 to 31.6 +/- 3.1 mm Hg, and pulmonary vascular resistance (RL) from 810 +/- 226 to 386 +/- 69 dyn. s. cm(-)(5) (p < 0.05, respectively). Systemic arterial pressure, arterial oxygen saturation, and pulmonary right-to-left shunt flow, measured by multiple inert gas analysis, were not significantly changed. Inhaled NO similarly resulted in selective pulmonary vasodilatation, with RL decreasing from 726 +/- 217 to 458 +/- 81 dyn. s. cm(-)(5). In contrast, both intravenous PGI(2) and CAAs were not pulmonary selective, resulting in a significant drop in arterial pressure. In addition, PGI(2) infusion caused a marked increase in shunt flow. Long-term therapy with aerosolized iloprost (long-acting PGI(2) analog) resulted in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure. We concluded that, in pulmonary hypertension secondary to lung fibrosis, aerosolization of PGI(2) or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure. Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis.

Topics: Administration, Inhalation; Adult; Aged; Atrial Function, Right; Calcium Channel Blockers; Drug Therapy, Combination; Epoprostenol; Female; Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Lung; Male; Middle Aged; Nifedipine; Nitric Oxide; Pulmonary Fibrosis; Pulmonary Gas Exchange; Pulmonary Wedge Pressure; Vascular Resistance; Vasodilator Agents; Ventilation-Perfusion Ratio; Vital Capacity

Severe pulmonary hypertension is a risk factor for mortality, due to increased postoperative right ventricular failure, in a heart transplant patient. Elevated pulmonary vascular resistance (PVR) in heart transplant candidates can be reduced using a left ventricular assist device or medical therapy. This study analysed the effect of inhaled iloprost and oral sildenafil combination therapy (ilo-sil) on pulmonary haemodynamic parameters in patients with secondary pulmonary hypertension.. Between May 2011 and April 2014, 25 patients who were unresponsive to reversibility test and PVR >3.5 Wood units (WU) during right heart catheterisation were included in this study. After 6 months of oral sildenafil (3 × 20 mg/day) and inhaled iloprost (6 × 5 μg/day) combination therapy, second right heart catheterisations were performed and eligibility for heart transplant was evaluated.. Repeat right heart catheterisation revealed that there was a significant decrease in the PVR from 5.4 ± 1.6 WU to 3.54 ± 2.5 WU (p<0.001), with trans-pulmonary gradient from 13.7 ± 5.6 to 11.46 ± 6.64 (p=0.042), and mean cardiac index (CI) increasing non-significantly from 1.45 ± 0.51 L/min/m2 to 1.82 ± 0.60 (p=0.157). The mean sPAP was initially 57.54 ± 14.79 mmHg and fell to 52.93 ± 16.83 mm Hg (p=0.03). Twenty (20) (80%) patients were enrolled in the waiting list since their PVR values decreased to <3.5 WU. Of these 20 patients, one had undergone heart transplant and four were bridged to transplant with mechanical circulatory support devices.. After a decrease in PVR with ilo-sil combination therapy for patients with severe pulmonary hypertension, these patients may become candidates for heart transplant without bearing additional risk. Ilo-sil combination therapy could be a viable option with which to evaluate the reversibility of PVR.

Topics: Administration, Inhalation; Administration, Oral; Adult; Cardiac Catheterization; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Iloprost; Male; Middle Aged; Retrospective Studies; Sildenafil Citrate; Treatment Outcome; Vascular Resistance; Vasodilator Agents

Systemic artery to pulmonary artery fistulas (SA-PAFs), are extremely rare in people without congenital heart disease. In this group of patients pulmonary arterial hypertension was reported in the single case. Then, we describe a case of multiple SA-PAFs, which were the cause of severe nonreversible arterial pulmonary hypertension in a patient who had a right-sided pneumothorax 35 years earlier.. 52-year-old male Caucasian patient with echocardiographically confirmed pulmonary hypertension (PH) was admitted to cardiology department due to exertional dyspnea and signs of right ventricle failure. Routine screening for causes of secondary PH was negative. Right heart catheterization (RHC) confirmed a high degree arterial PH [mean pulmonary artery pressure (mPAP); 50,6 mmHg, pulmonary wedge pressure (PWP); 11,3 mmHg, pulmonary vascular resistance (PVR); 11,9 Wood's units (WU)] irreversible in the test with inhaled nitric oxide. Oxygen saturation (SaO. Non-congenital SA-PAFs are extremely rare, however, they should be excluded in patients with pulmonary arterial hypertension and history of inflammatory or infectious disease of the lung and pleura, pneumothorax, cancer or Takayashu's disease and after chest trauma.

Topics: Arterio-Arterial Fistula; Cardiac Catheterization; Computed Tomography Angiography; Familial Primary Pulmonary Hypertension; Fatal Outcome; Heart Failure; Humans; Iloprost; Lung; Male; Middle Aged; Pneumothorax; Pulmonary Artery; Pulmonary Wedge Pressure; Sildenafil Citrate; Vascular Resistance

To investigate the efficacy and safety of inhaled iloprost on top of other pulmonary hypertension (PH) specific therapies for patients with PH and severe right heart failure.. We consecutively enrolled WHO functional class IV patients with PH and chronic thromboembolic pulmonary hypertension (CTEPH) in Shanghai Pulmonary Hospital from January 2011 to January 2013. Inhaled iloprost was administrated to all enrolled patients, oral endothelin antagonist receptors (ERAs) and/or type 5 phosphodiasterase inhibitors (PDE5-I) were also used as basis therapies. The in-hospital outcomes and the changes of right heart functional parameters were observed.. Twenty-four patients with PH and 5 patients with CTEPH were enrolled. After a mean treatment duration of (23 ± 13) days, 3 patients dead and significant improvement was observed in the remaining 26 patients. Compared with the baseline, heart rate decreased from (99 ± 14) to (91 ± 12) bpm (P = 0.001), plasma NT-proBNP level decreased from 5 823 (3 029-13 248) to 3 220 (1 678-6 720) ng/L (P < 0.001), tricuspid annular plane systolic excursion (TAPSE) increased from (1.3 ± 0.4) to (1.4 ± 0.3) cm (P = 0.018), right ventricular diameter decreased (left-to-right diameter from (57 ± 11) to (53 ± 10) mm, P = 0.040, and superoinferior diameter from (69 ± 11) to (64 ± 16) mm, P = 0.027), Tbil also decreased from (41 ± 34) to (26 ± 17) µmol/L (P < 0.001). No severe side effects were observed.. The strategy of inhaled iloprost on top of other PAH-specific target therapy medications is effective and safe for PH patients with severe right heart failure.

Topics: Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Natriuretic Peptide, Brain; Peptide Fragments; Vasodilator Agents; Ventricular Dysfunction, Right

Topics: Administration, Inhalation; Critical Care; Diuretics; Furosemide; Heart Failure; Humans; Hydrazones; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Pyridazines; Simendan; Thromboembolism; Vasodilator Agents; Ventricular Dysfunction, Right

Prostanoid-modulatory approaches in heart failure patients have displayed effects which may seem to be mutually incompatible. Both treatment with prostanoids and inhibition of prostanoid synthesis have resulted in increased mortality in heart failure patients. Currently, it is unknown if prostanoids mediate contractile effects in failing human heart and if this can explain some of the clinical effects seen after prostanoid modulatory treatments. Therefore, the objectives of this study were to determine if prostanoids could elicit direct inotropic responses in human ventricle, and if so to determine if they are modified in failing ventricle. Contractile force was measured in left ventricular strips from non-failing or failing human and rat hearts. The ratio of phosphorylated to non-phosphorylated myosin light chain 2 (MLC-2) was measured by Western blotting in myocardial strips, and the levels of prostanoid FP receptor mRNA and protein were measured in rat by real-time RT-PCR and receptor binding assays. In non-failing human hearts, prostanoids evoked a positive inotropic effect and an increase of MLC-2 phosphorylation which was absent in failing human hearts. In failing rat heart, the prostanoid FP receptor-mediated inotropic response and prostanoid FP receptor-density was reduced by ~40-50% compared to non-failing rat heart. Prostanoids mediate a sustained positive inotropic response in non-failing heart, which appears to be down regulated in failing heart. The pathophysiological significance of changes in prostanoid-mediated inotropic support in the failing heart remains to be determined.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alprostadil; Animals; Cardiac Myosins; Child; Disease Models, Animal; Female; Heart Failure; Heart Ventricles; Humans; Iloprost; Male; Middle Aged; Myocardial Contraction; Myosin Light Chains; Prostaglandins F, Synthetic; Rats; Receptors, Prostaglandin; Ventricular Function

Pulmonary hypertension and right ventricular (RV) dysfunction may complicate the implantation of a left ventricular assist device (LVAD). We examined whether inhaled vasodilators can sufficiently reduce RV afterload, avoiding the need for temporary RV mechanical support.. The study includes 7 patients with RV dysfunction after LVAD insertion. Treatment consisted of inotropes, inhaled nitric oxide (10 ppm), and iloprost (10 μg) in repeated doses. Full hemodynamic profile was obtained before inhalation, during administration of inhaled NO alone (before and after iloprost), as well as after the first two doses of inhaled iloprost. Tricuspid annular velocity was estimated at baseline and before and after adding iloprost.. There was a statistically significant reduction in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP), RV systolic pressure, and pulmonary capillary wedge pressure, and a considerable increase in LVAD flow, LV flow rate index, and tricuspid annular velocity at all points of evaluation versus baseline. By the end of the protocol, MPAP/mean systemic arterial pressure, and PVR/systemic vascular resistance ratios were reduced by 0.17±0.03 (95% confidence interval, 0.10 to 0.25, p=0.001) and 0.12±0.025 (95% confidence interval, 0.06 to 0.18; p=0.003), respectively. The tricuspid annular velocity increased by 2.3±0.18 cm/s (95% confidence interval, 1.83 to 2.73 cm/s; p<0.001). Pairwise comparisons before and after iloprost showed an important decrease in PVR (p=0.022), MPAP (p=0.001), pulmonary capillary wedge pressure (p=0.002), and RV systolic pressure (p<0.001), and a rise in tricuspid annular velocity (p=0.008).. Inhaled vasodilators mainly affected the pulmonary vasculature. Combination treatment with inhaled NO and iloprost sufficiently decreased PVR and MPAP on the basis of an additive effect, improved RV function, and avoided the need for RV assist device.

Topics: Administration, Inhalation; Adult; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nitric Oxide; Pulmonary Wedge Pressure; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival Rate; Treatment Outcome; Vascular Resistance; Ventricular Dysfunction, Right

Topics: Female; Heart Failure; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Iloprost; Male; Nitric Oxide; Ventricular Dysfunction, Right

To determine the effects of inhaled nitric oxide (NO) and aerosolized iloprost on pulmonary hemodynamics and lung edema formation in a rat model of pulmonary hypertension due to congestive heart failure (CHF).. Prospective, randomized, controlled study.. Research laboratory.. One hundred sixty male Sprague-Dawley rats.. CHF was induced by supracoronary aortic banding whereas sham-operated rats served as controls. CHF rats or controls inhaled NO, aerosolized iloprost, or 0.9% NaCl for 3 minutes each. Additional CHF groups received intravenous infusions of iloprost, sodium nitroprusside, or 0.9% NaCl. For prolonged drug administration over 150 minutes, NO was inhaled continuously whereas aerosolized iloprost was administered for 3 minutes each at 45-minute intervals.. Dose-response relations in rats with CHF showed a maximal pulmonary-selective reduction in blood pressure at 20 ppm NO and 2.5 microg/mL aerosolized iloprost, with iloprost therapy resulting in a greater decrease in pulmonary arterial pressure (PAP). At these doses, both vasodilators decreased pulmonary vascular resistance and increased venous oxygen saturation (Svo2) in the absence of systemic hemodynamic effects. No pulmonary or systemic effects were detected in rats with CHF inhaling 0.9% NaCl or in control rats inhaling NO or iloprost. Intravenous infusion of iloprost or sodium nitroprusside not only reduced pulmonary but also systemic vascular resistance. During prolonged inhalation, NO caused a stable reduction in PAP, whereas PAP decreased even further during repetitive iloprost inhalations. After 150 minutes, iloprost-treated rats had a higher Svo2 and lesser edema as compared with animals with CHF inhaling NO or untreated rats with CHF, although differences in wet/dry weight ratio did not reach statistical significance (p < 0.06).. Inhaled vasodilators may offer an effective, safe, and pulmonary-selective strategy for the treatment of pulmonary hypertension in left heart disease, and inhaled iloprost may be superior to NO in this condition.

Topics: Administration, Inhalation; Aerosols; Animals; Heart Failure; Hypertension, Pulmonary; Iloprost; Male; Nitric Oxide; Rats; Rats, Sprague-Dawley; Vasodilator Agents

Iloprost, as a stable analog of endogenous prostacyclin, has far-reaching pharmacological effects. For several years already it has been used successfully in its intravenous and inhalative forms for treating patients with pulmonary hypertension (PH). Since the development of efficient nebulizers that guarantee a constant output of the effective agent, inhalative iloprost has become an important alternative in the drug treatment of PH. Inhalative iloprost is an effective and safe partner for other classes of substances in combination therapy, which is becoming ever more frequently necessary. In addition, it is also used in the acute testing of pulmonary vasoreactivity and in intensive care therapy of manifest right heart failure.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Critical Care; Drug Therapy, Combination; Female; Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Infant; Infant, Newborn; Male; Middle Aged; Pulmonary Circulation; Vasodilator Agents

Increased pulmonary vascular resistance causing pulmonary artery hypertension is a major problem in the treatment of congenital diaphragmatic hernia with a strong association to mortality. We here report a patient with intractable pulmonary hypertension at 4 weeks of age unresponsive to conventional treatment. After administration of the platelet-derived growth factor (PDGF) receptor antagonist imatinib, pulmonary artery pressure gradually decreased to acceptable levels and the patient's clinical condition gradually improved.

Topics: Benzamides; Bosentan; Combined Modality Therapy; Continuous Positive Airway Pressure; Diuretics; Enteral Nutrition; Extracorporeal Membrane Oxygenation; Heart Failure; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Hypoxia; Iloprost; Imatinib Mesylate; Infant, Newborn; Male; Nitric Oxide; Piperazines; Protein Kinase Inhibitors; Purines; Pyrimidines; Receptors, Platelet-Derived Growth Factor; Sildenafil Citrate; Sulfonamides; Sulfones

Chronic left-heart failure is often associated with the development of pulmonary venous hypertension. In heart transplant candidates this is of great significance because the healthy donor heart has to compensate the increased right-ventricular afterload. Right-ventricular dysfunction is still responsible for 19% of all early deaths after orthotopic heart transplantation. Careful preoperative assessment of pulmonary vascular resistance by right-heart catheterization is essential. Reversibility testing is generally carried out to clarify therapeutic options for the post-transplant period. The objective of this case series is to report our institutional experience with inhaled iloprost compared to the common used oxygen/nitroglycerin method for reversibility testing.. Right-heart catheterization was performed in 23 patients with severely impaired left-ventricular function (EF < or = 25%, pVO2 < or = 14 ml/kg/min, NYHA III or IV) with combined pulmonary venous hypertension (TPG > 12 mm Hg and or PVR > 250 dyn x s x cm(-5)). An intraindividual comparison was performed between of the hemodynamic effect with oxygen/nitroglycerin s.l. and inhaled iloprost.. The transpulmonary gradient fell significantly from an initial 16 mm Hg to 13 mm Hg on oxygen/nitroglycerin s.l. compared to 10 mm Hg on inhaled iloprost. Pulmonary vascular resistance fell significantly from an initial 344 dyn x s x cm(-5) to 270 dyn x s x cm(-5) on oxygen/nitroglycerin s.l. compared to 209 dyn x s x cm(-5) on inhaled iloprost. On inhaled iloprost a moderate systemic effect was noticed.. In heart transplant candidates with pulmonary venous hypertension reversibility testing with inhalation of iloprost is a save method and significantly more effective than the combination of inhaled oxygen plus nitroglycerin s.l.

Topics: Administration, Inhalation; Adult; Aged; Cardiac Catheterization; Female; Heart Failure; Heart Transplantation; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nitroglycerin; Oxygen Inhalation Therapy; Pilot Projects; Vascular Resistance; Vasodilator Agents

Topics: Drug Administration Schedule; Electrocardiography; Fatal Outcome; Female; Heart Failure; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Infant, Newborn; Intracranial Aneurysm; Male; Nitric Oxide; Oxygen; Pneumothorax; Respiration, Artificial; Vasodilator Agents

Pulmonary hypertension secondary to valvular heart disease is a cause of acute right heart failure during valve replacement operations. This study compares the hemodynamic effects of intravenous use of iloprost and nitroglycerin in patients with pulmonary hypertension undergoing valvular replacement surgery. We sought to determine the acceptable doses of these medications for use in surgery to decrease mean pulmonary artery pressure to <30 mmHg without causing systemic side effects. The plasma nitric oxide levels that were obtained from pulmonary mixed venous blood have been compared to demonstrate the difference in the action mechanism of these drugs.. Eighteen patients undergoing mitral or aortic and mitral valvular replacement with pulmonary hypertension >25 mmHg were included in the study. The 2 groups received iloprost or nitroglycerin via a central pulmonary catheter, and the hemodynamic parameters were evaluated before incision (T1), 10 minutes after chest opening (T2), and 5 minutes and 20 minutes after cardiopulmonary bypass (T3 and T4). The plasma nitric oxide levels were obtained from the mixed venous blood at the T1 and T4 intervals.. The data have been analyzed for each group and for repeated measurements of hemodynamic parameters at T1-T4 time points. The analysis of hemodynamic parameters before (T1 and T2) and after (T3 and T4) bypass showed similar responses depending on the use of either iloprost or nitroglycerin. The administration of iloprost after bypass (T3) at a dosage of 1.25 to 2.5 ng/kg per minute reduced mean pulmonary artery pressure (from 28.8 +/- 7.89 to 20.63 +/- 6.39 mmHg) and pulmonary vascular resistance (from 226.88 +/- 101.93 to 118.00 +/- 82.36 dyn sec cm -5) better than nitroglycerin at a dosage of 0.5 to 1 microg/kg per minute (from 23.20 +/- 5.20 to 18.50 +/- 5.10 mmHg and from 160.80 +/- 39.76 to 137.40 +/- 56.54 dyn sec cm -5, respectively). Iloprost causes significant increase in cardiac output (from 4.91 +/- 0.91 to 5.49 +/- 0.91 L/min) compared to nitroglycerin (from 5.23 +/- 0.80 to 5.27 +/- 0.74 L/min). The plasma nitric oxide levels of the iloprost group did not show an increase from T1 to T4, whereas the nitroglycerin group levels did (P <.05).. Intravenous use of both iloprost and nitroglycerin effectively reduces mean pulmonary artery pressure, although only the iloprost group was accompanied by an increase in cardiac output. During operation, where abrupt management of pulmonary hypertension is required, systemic use of iloprost or nitroglycerin at appropriate doses via a pulmonary artery catheter offers adequate relief of hypertension and is well tolerated without any significant adverse effects. The plasma nitric oxide levels did not rise with the use of iloprost.

Topics: Adult; Aged; Antihypertensive Agents; Cardiac Output; Female; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Male; Middle Aged; Nitric Oxide; Nitroglycerin; Vasodilator Agents

Severe portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis and carries a poor prognosis. In the last years, intravenous (IV) epoprostenol has been suggested to be the optimal medical treatment for PPHTN, and recently oral bosentan has been shown to be efficacious and safe in selected patients with PPHTN. We report a case of PPHTN suffering from recurrent right heart failure while on treatment with IV iloprost, which was successfully managed by combination therapy with IV iloprost plus oral bosentan, providing sustained cardiopulmonary stabilization for at least two years. This report documents the first case of a patient with PPHTN successfully treated with the combination of IV iloprost and oral bosentan over an extended period. Thus, combination therapy with IV iloprost and oral bosentan might be a promising new option for selected patients suffering from PPHTN and recurrent right heart failure.

Topics: Administration, Oral; Adult; Antihypertensive Agents; Bosentan; Drug Therapy, Combination; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Hypertension, Portal; Hypertension, Pulmonary; Iloprost; Injections, Intravenous; Liver Cirrhosis, Alcoholic; Male; Recurrence; Sulfonamides; Time Factors

Significant pulmonary hypertension is a predictor of postoperative right heart insufficiency and increased mortality in patients undergoing orthotopic heart transplantation. Since the use of iv vasodilators is limited by their systemic effects, we evaluated the pulmonary and systemic hemodynamic effects of inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated pulmonary vascular resistance (PVR).. Twenty-nine male heart transplant candidates because of dilated or ischemic cardiomyopathy with elevated PVR were included in the study. After assessing baseline hemodynamics, 50 micro g aerosolized IP were administered by inhalation.. Inhalation of iloprost reduced PVR index (PVRI; 416 +/- 180 vs 349 +/- 173 dyn x sec(-1) x m(-2) x cm(-5); P < 0.01) and mean pulmonary artery pressure (MPAP; 28.6 +/- 9 vs 24.2 +/- 9.1 mmHg; P < 0.01), but did not affect blood pressure or systemic vascular resistance. An additional improvement of ventricular performance with an increase of cardiac index (CI; 2.8 +/- 0.7 vs 2.6 +/- 0.7 L x min(-1) x m(-2); P < 0.05) and a decrease of pulmonary capillary wedge pressure (PCWP; 15.6 +/- 6.8 vs 12.8 +/- 7.1 mmHg; P < 0.01) was observed after inhalation of IP.. Inhaled aerosolized iloprost effectively reduces MPAP and is accompanied by an increase in CI and stroke index. Further advantages of iloprost inhalation are the lack of adverse reactions and ease of administration. Iloprost may be a useful drug to screen for vascular reactivity in cardiac transplantation patients.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Chronic Disease; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nitric Oxide

Perioperative acute right heart failure after orthotopic heart transplantation contributes significantly to morbidity and mortality. Vasodilators administered intravenously may decrease pulmonary vascular resistance, but also affect systemic circulation. A decrease of mean arterial pressure will result in reduced right coronary blood flow and deterioration of right ventricular performance. Vasodilators administered by inhalation, i.e. nitric oxide and prostacyclin, are attractive due to a more selective effect on the pulmonary circulation. This is the first report on the use of aerosolized iloprost, a long-acting prostacyclin analogue, applied for treatment of postoperative right heart failure in cardiac transplantation. After uneventful surgery, a heart transplant recipient was extubated on the first postoperative day and exhibited right heart failure on the following day. Standard treatment did not resolve this clinical problem sufficiently. A trial with inhalation of iloprost (16 microg per inhalation cycle, applied six times per day) was initiated. Iloprost inhalation resulted in a sufficient decrease of pulmonary vascular resistance (-23.5%), while cardiac index (+24.0%) and mixed venous saturation (+9.0%) increased. No profound effect on the systemic vascular resistance was observed (-2.8%). Iloprost inhalation may be an effective alternative to nitric oxide in the intensive care management of acute right heart failure after orthotopic heart transplantation. Due to the prolonged effect on the pulmonary vascular resistance, iloprost is especially useful for extubated patients.

Topics: Administration, Inhalation; Central Venous Pressure; Heart Failure; Heart Transplantation; Humans; Iloprost; Male; Middle Aged; Postoperative Complications; Pulmonary Circulation; Vascular Resistance; Vasodilator Agents

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the effects of the prostacyclin-derivative iloprost (1.5-150 ng/kg/min) in seven conscious dogs before and after induction of heart failure by right ventricular pacing (250/min. 10 days). In healthy dogs, iloprost (150 ng/kg/min) decreased mean arterial blood pressure (MAP) (-45%) by a decrease in total peripheral resistance (TPR) (-55%), and increased cardiac output (CO) (+24%) and heart rate (HR) (+20%) with no effect on right atrial and pulmonary arterial pressures (RAP, PAP). Plasma norepinephrine (NE) (+47%), renin (+351%), and aldosterone (+126%) were increased. Urine flow (-70%) and Na excretion (-53%) were decreased. Iloprost (15 ng/kg/min) increased renal blood flow (RBF) (+29%), but did not change glomerular filtration rate (GFR). In dogs with heart failure, iloprost decreased arterial BP (-31%), TPR (-42%) and pulmonary vascular resistance (-28%) and increased CO (+29%), with no change in RAP and PAP. Plasma NE (+34%), renin (+385%), and aldosterone (+146%) were increased. RBF was unchanged. GFR (-24%) and filtration fraction (FF) (-30%) were decreased, as was urine flow (-65%). In experimental heart failure, iloprost is a potent arteriolar dilator, increasing CO with no preload effect. These beneficial effects are limited, however, by further neurohumoral activation and deterioration of renal function.

Topics: Analysis of Variance; Animals; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Hormones; Iloprost; Renal Circulation