iloprost and Pulmonary-Embolism

Chronic thromboembolic pulmonary hypertension is one of the most common forms of pulmonary hypertension (PHT), but frequently remains undiagnosed and untreated. Pulmonary thrombendarterectomy is the treatment of choice, but only about 50 % of such patients are operable. About 15 % of patients are not improved by surgery, usually because of residual PHT with advanced vascular changes. Drug treatment has favorable effects in inoperable forms and in postoperative recurrence of PHT.

Topics: Antihypertensive Agents; Bosentan; Endarterectomy; Humans; Hypertension, Pulmonary; Iloprost; Piperazines; Pulmonary Embolism; Purines; Recurrence; Sildenafil Citrate; Splenectomy; Sulfonamides; Sulfones; Vasodilator Agents

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potential consequence to pulmonary embolism. The histologic picture is similar to idiopathic pulmonary hypertension (IPAH) suggesting that vascular remodeling also contributes to CTEPH. The treatment of choice is pulmonary endarterectomy. However, this treatment option is not adequate for all patients with CTEPH. Currently, no data exist on standard vasodilative therapy for CTEPH. Intravenous and oral prostanoids, both well-known vasodilators in IPAH, have been used with promising results, whereas the same has not been consistently observed for inhaled iloprost.. In this study, we examined acute hemodynamic effects of inhaled iloprost in patients with CTEPH.. In a prospective study, right heart catheterization was performed in 20 patients (mean age 56 years, New York Heart Association class II-IV) at the time of diagnosis of CTEPH. Pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac output (CO), mean systemic arterial pressure (MAP) and oxygen partial pressure (PaO(2)) were obtained before and 20 min after inhaling 5 mug iloprost. Subsequently, all patients were evaluated for pulmonary endarterectomy. Six patients were eligible for surgery.. Significant changes in pulmonary and systemic hemodynamics were observed following the inhalation of iloprost (before to after inhalation): PVR: 1,057 +/- 404.3 to 821.3 +/- 294.3 dyn.s.cm(-5), p < 0.0001; mPAP: 50.55 +/- 8.43 to 45.75 +/- 8.09 mm Hg, p = 0.0002; CO: 3.66 +/- 1.05 to 4.05 +/- 0.91 l/min, p < 0.0106. MAP and PaO(2) decreased significantly (MAP: 94.15 +/- 11.58 to 89.45 +/- 14.29 mm Hg, p = 0.0111; PaO(2): 7.33 +/- 1.17 to 6.64 +/- 1.25 kPa, p = 0.0260).. Hemodynamic changes directly following inhalation of iloprost suggest a significant contribution of a reversible component of vasoconstriction to pulmonary arterial hypertension in patients with CTEPH.

Topics: Administration, Inhalation; Adult; Aged; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Lung; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Vasoconstriction; Vasodilator Agents

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the major classes of pulmonary hypertensive disorders according to the World Health Organization; both lead to right heart failure and death. A better understanding of disease mechanisms has led to the suggestion that the thromboembolic and nonthromboembolic types of pulmonary hypertension may share pathophysiologic features. We therefore compared acute vasoreactivity and proximal pulmonary artery compliance in patients with PAH and CTEPH during the initial diagnostic heart catheterization.. Right heart catheterization using a flow-directed Swan-Ganz catheter was performed in patients with CTEPH (n = 22) and PAH (n = 35). Pulmonary hemodynamics were assessed at baseline, during the inhalation of 40 ppm of nitric oxide, and 30 min after the inhalation of 10 mug of iloprost. To assess the proximal pulmonary artery compliance, the pulse pressure (PP) [systolic-diastolic pressure] and the fractional PP (PPf) [divided by the mean pressure] were calculated.. Both vasodilators produced similar hemodynamic improvement, and the difference between CTEPH and PAH was not significant. The baseline PP and PPf did not vary between the two groups.. Patients with PAH and CTEPH show similar acute vasoreactivity to inhaled nitric oxide and iloprost, and have similar pulmonary artery compliance. These findings support the presence of some shared pathophysiologic pathways in both disorders and may lead to therapeutic implications in patients with inoperable CTEPH.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Bronchodilator Agents; Cardiac Catheterization; Chronic Disease; Compliance; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Lung; Middle Aged; Nitric Oxide; Pulmonary Artery; Pulmonary Embolism; Vasodilation; Vasodilator Agents; World Health Organization

Pulmonary arterial hypertension (PAH), defined as elevated pulmonary arterial pressure and pulmonary vascular resistance, is an end-point of a variety of conditions. The only therapy that has been shown to improve both quality of life and survival is intravenous prostacyclin (prostaglandin I2 (PGI2), epoprostenol). The effect of long-term aerosolized iloprost (Ilomedin, Schering, Berlin, Germany and Vienna, Austria), a stable prostacyclin analogue and potent vasodilator, on haemodynamics and functional status was investigated in 12 patients with severe pulmonary hypertension. Haemodynamic measurements and vasodilator testing by right heart catheterization were performed prior to and after long-term iloprost inhalation therapy. Haemodynamic improvement or increased exercise tolerance was not observed in any of the patients. After a mean+/-SD treatment period of 10+/-5 months, mean+/-SD pulmonary vascular resistance had increased from 11+/-3 Wood Units (mmHg.L(-1).min) to 13+/-4 Wood Units, with unchanged arterial oxygen saturation (92+/-4%, versus 91+/-4%). Within the study period, three patients went into right heart failure and had to be placed on intravenous epoprostenol. The authors conclude that inhaled iloprost in addition to conventional therapy in the presently recommended dose of 100 microg.day(-1) delivered in 8-10 2 h portions, is not an efficient vasodilator therapy in severe pulmonary hypertension. It remains to be shown whether dose increases and/or combination protocols will be effective, or whether inhalation of iloprost may be safe for selected cases of pulmonary hypertension.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Blood Pressure; Cardiac Output; Chronic Disease; Epoprostenol; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Male; Middle Aged; Oxygen; Prospective Studies; Pulmonary Circulation; Pulmonary Embolism; Vascular Resistance; Vasodilator Agents

Acute vasoreactivity testing (AVT) which reflects the compliance of the pulmonary vascular bed has been proven to be of prognostic value. The purpose of the present study is to explore the sex differences of hemodynamics during the AVT and their impact on event-free survival in patients with chronic thromboembolic pulmonary hypertension (CTEPH).. Eighty-six patients underwent a right heart catheterization and AVT at Shanghai Pulmonary Hospital from February 2009 to February 2018. Univariate and multiple stepwise regression analysis were performed to determine the predictors of independent event-free survival, and receiver operating characteristic curve was plotted to determine the cut-off value of independent parameters in CTEPH.. There were no significant differences in both demographics and hemodynamics between male and female patients with CTEPH. Except ΔPVR/PVR showed a significantly higher difference in female than male patients (P = 0.034). Male patients had higher mRAP of pre- and post-AVT than female patients in the event-free subgroup, while, female patients showed higher PVR of pre-AVT than male patients in the event subgroup (P < 0.05). The mRAP and SvO. Hemodynamics during the AVT varied between male and female patients with CTEPH. Both sexes displayed unique hemodynamic responses that were independently able to predict event-free survival. Therefore, better estimates of prognosis in CTEPH can be made when sex differences are also taken into consideration.

Topics: Administration, Inhalation; Adult; Aged; Cardiac Catheterization; China; Chronic Disease; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Lung; Male; Middle Aged; Predictive Value of Tests; Prognosis; Progression-Free Survival; Pulmonary Embolism; Pulmonary Wedge Pressure; Regression Analysis; ROC Curve; Sex Characteristics; Vasodilator Agents

Topics: Academies and Institutes; Administration, Inhalation; Angioplasty, Balloon; Antihypertensive Agents; Asian People; Bone Morphogenetic Protein Receptors, Type II; Bosentan; Calcium Channel Blockers; Cardiology; Cooperative Behavior; Endothelin Receptor Antagonists; Female; Growth Differentiation Factor 2; Guidelines as Topic; Humans; Iloprost; Mutation; Phenylpropionates; Pulmonary Arterial Hypertension; Pulmonary Embolism; Pulmonary Medicine; Pyridazines; Takayasu Arteritis; Vasodilator Agents

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subset of pulmonary hypertension caused by acute and recurrent pulmonary emboli. Pulmonary thromboendarterectomy is the treatment of choice, but 10-50% of patients are ineligible for this procedure. We describe the case of a 25-year-old, morbidly obese (228-kg, body mass index 83.5 kg/m(2) ) pregnant woman (G3 P2 ) who presented at 24 weeks' gestation; bilateral pulmonary angiography revealed filling defects and confirmed the diagnosis of CTEPH. The patient was evaluated and deemed to present too high of a risk for pulmonary thromboendarterectomy, so a multidisciplinary team initiated medical therapy. Sildenafil 20 mg orally 3 times/day was started at week 24 of gestation, and inhaled iloprost was added at 26 weeks and titrated to 5 µg inhaled every 2 hrs in order to optimize hemodynamic status prior to a cesarean section delivery scheduled to be performed 6 weeks later. At 32 weeks of gestation, the patient's pulmonary arterial systolic pressure was 77 mm Hg, right atrial pressure was 15 mm Hg, and pulmonary capillary wedge pressure of 16 mm Hg, and a healthy 1741-g male infant was delivered by cesarean section. The patient was transferred back to the medical intensive care unit in stable condition and discharged home 9 days following the procedure. Pharmacotherapeutic strategies for patients with CTEPH who become pregnant are limited to phosphodiesterase type 5 inhibitors and prostacyclin analog therapies due to the teratogenicity of the other drug classes used to treat the disorder (endothelin receptor antagonists and soluble guanylate cyclase stimulators). To our knowledge, this is the first case report of inhaled iloprost use in addition to oral sildenafil to improve patient symptomatology and hemodynamics during the peripartum period of a young pregnant patient with inoperable CTEPH. This drug therapy was used safely, with no noted adverse effects to the newborn or to the patient.

Topics: Administration, Inhalation; Adult; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Iloprost; Pregnancy; Pregnancy Complications; Pulmonary Embolism

Topics: Administration, Inhalation; Humans; Hypertension, Pulmonary; Iloprost; Nebulizers and Vaporizers; Pulmonary Embolism; Tomography, Spiral Computed; Treatment Outcome; Ultrasonography; 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

This case report describes the treatment of reperfusion lung oedema after pulmonary thromboendarterectomy using intravenous iloprost infusion in a 52-year-old woman diagnosed with chronic thromboembolic pulmonary hypertension.

Topics: Endarterectomy; Female; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Edema; Pulmonary Embolism; Reperfusion Injury

Topics: Aged; Chronic Disease; Dose-Response Relationship, Drug; Endarterectomy; Humans; Hypertension, Pulmonary; Iloprost; Male; Platelet Aggregation Inhibitors; Prostaglandins; Pulmonary Embolism

Acute pulmonary hypertension with life-threatening right heart failure may complicate the postoperative course following cardiothoracic surgery. Both inhaled nitric oxide and inhaled iloprost, a stable analogue of prostacyclin, have been used frequently for this purpose in acute pulmonary hypertension of various origins. We present a case of a patient with acute pulmonary hypertension and severely impaired gas exchange following pulmonary thrombo-endarterectomy. Therapy with one inhaled vasodilator alone did not satisfactorily abort a postoperative pulmonary hypertensive crisis and low-output syndrome due to right heart failure. Combined inhaled nitric oxide and inhaled iloprost, however, showed additive effects. Hence, the combination of both drugs may be reasonable in cases where the standard therapy fails. The effect has been demonstrated by means of continuous blood gas monitoring.

Topics: Administration, Inhalation; Adult; Drug Therapy, Combination; Endarterectomy; Humans; Hypertension, Pulmonary; Hypoxia; Iloprost; Male; Nitric Oxide; Pulmonary Embolism; Vasodilator Agents

Chronic thromboembolic pulmonary hypertension (CTPH) is an uncommon complication of pulmonary embolism. The treatment of choice is thromboendarterectomy, a safe and effective surgical procedure in expert hands. However, a fair number of patients are not considered candidates for thromboendarterectomy or do not accept the risk involved. Such patients may respond well to prostacyclin or its derivatives. In recent years new vasodilator drugs administered by a variety of routes have appeared on the market. These drugs have been studied mainly for their effects on primary pulmonary hypertension or hypertension associated with connective-tissue diseases. Few trials have assessed their efficacy in patients with CTPH, however. We report 2 cases of CTPH in which thromboendarterectomy was rejected. Neither of the patients responded to the conventional treatment of anticoagulants, diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors, but they did respond very well clinically, hemodynamically, and functionally to an inhaled prostacyclin analog, iloprost. We discuss the effects of iloprost in patients with CTPH, its mechanism of action, and its use as a potential pharmacological alternative to thromboendarterectomy. We also discuss new pulmonary vasodilators in general.

Topics: Aged; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Pulmonary Embolism; Vasodilator Agents

In primary pulmonary hypertension, aerosolized prostanoids selectively reduce pulmonary vascular resistance and improve right ventricular function. In this study, hemodynamic effects of inhaled iloprost, a stable prostacyclin analogue, were evaluated in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and early after pulmonary thromboendarterctomy (PTE).. Ten patients (mean age 49 years old [32 to 70 years old], New York Heart Association functional class III and IV) received a dose of 33 micro g aerosolized iloprost immediately before surgery (T1), after intensive care unit admission (T2), and 12-hours postoperatively (T3). Effects on pulmonary and systemic hemodynamics and gas exchange were recorded and compared with preinhalation baseline values.. Preoperatively, inhaled iloprost did not significantly change mean pulmonary artery pressure (mPAP), cardiac index (CI), or pulmonary vascular resistance (PVR). Postoperatively, inhaled iloprost induced a significant reduction of mPAP and PVR and a significant increase of CI at T2 and T3. Preinhalation versus postinhalation PVR was as follows: at T1, 847 versus 729 dynes. s. cm(-5), p = 0.45; at T2, 502 versus 316 dynes. s. cm(-5), p = 0.008; and at T3, 299 versus 227 dynes. s. cm(-5), p = 0.004.. In patients with CTEPH, inhalation of iloprost elicits no significant pulmonary vasodilation before surgery, and may have detrimental effects on systemic hemodynamics. Postoperatively, it significantly reduces mPAP and PVR, and enhances CI. Following PTE, inhalation of iloprost is useful to improve early postoperative hemodynamics.

Topics: Administration, Inhalation; Adult; Aged; Chronic Disease; Endarterectomy; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Postoperative Period; Preoperative Care; Pulmonary Embolism; Vasodilator Agents

The authors report a case of massive pulmonary embolism revealing thrombocytopenia induced by a low molecular weight heparin (LMWH) initially proposed for the treatment of superficial phlebitis. The diagnosis was confirmed by in vitro aggregation tests and a fall in the platelet count when the LMWH was reintroduced. The outcome was clinically, angiographically and hematologically satisfactory in response to in situ treatment with prostaglandin, subsequently replaced by Vitamin K antagonists.

Topics: Fibrinogen; Heparin, Low-Molecular-Weight; Humans; Iloprost; Male; Middle Aged; Phlebitis; Platelet Count; Pulmonary Embolism; Radiography; Thrombocytopenia

A chemically stable prostacyclin analog, KP-10614 [(4z,16s)-4,5,18,18,19,19-hexadehydro-16,20-dimethyl-delta 6(9;alpha)-9(o)- methano-PGI1], has been compared with two other prostacyclin derivatives (Iloprost and TEI-7165) and one prostaglandin E1 derivative (OP-1206) with respect to ADP-induced in vitro aggregation of human platelets and ex vivo platelet aggregation in rats and dogs, given by bolus injection and i.v. infusion. These compounds were also tested on the systemic arterial blood pressure of rats and dogs. KP-10614 was the most potent inhibitor of in vitro platelet aggregation induced by ADP with IC50 of 1 nM among the compounds studied in this report, and it also showed ex vivo effectiveness at doses much lower than the other three compounds. KP-10614 was also orally active. At oral doses of 25, 50 and 100 micrograms/kg, this new compound caused a dose-dependent inhibition of ex vivo platelet aggregation in rats, whereas the other three compounds were effective only at 500 micrograms/kg or more. In addition, KP-10614 showed definite antithrombotic effects at a dose range of 0.1 to 1 microgram/kg i.v. in various thrombosis models in which platelet aggregation was mainly involved. These results indicate that KP-10614 possesses therapeutic potential in thrombotic diseases.

Topics: Administration, Oral; Alprostadil; Animals; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Collagen; Dogs; Epoprostenol; Female; Fibrinolytic Agents; Heart Rate; Humans; Iloprost; Infusions, Intravenous; Injections, Intravenous; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Pulmonary Embolism; Rats; Rats, Inbred Strains; Thrombocytopenia; Vasodilator Agents

We report the vascular surgical strategies and results in 13 patients with heparin-associated thrombocytopenia and describe useful in vitro techniques for the evaluation of anticoagulant therapy. Thirteen of 40 patients with heparin-associated thrombocytopenia had 18 cardiovascular procedures done to save life or limb. Greenfield filters were placed in eight patients to prevent pulmonary embolism. Eight patients had 10 arterial procedures, with alternative anticoagulation that used dextran or warfarin in five cases. In three cases iloprost, a derivative of prostacyclin and a potent platelet inhibitor, was infused intraoperatively and heparin was given. Both the use of alternative anticoagulants and platelet suppression by iloprost were clinically effective strategies. The concurrent measurement of plasma levels of beta-thromboglobulin and fibrinopeptide A in two patients confirmed that both approaches can successfully prevent activation of platelets and plasma coagulation during arterial surgery. One operative death occurred; all vascular reconstructions remained patent at 3 to 6 months. In two patients who received heparin alone for arterial surgery, both procedures resulted in thrombosis and limb loss. When major venous thromboembolism is complicated by heparin-associated thrombocytopenia, insertion of a Greenfield vena cava filter should be considered if there is significant risk of pulmonary embolism. When necessary, arterial surgery is feasible in patients with heparin-associated thrombocytopenia if alternative anticoagulation or adequate suppression of platelet reactivity can be achieved.

Topics: Dextrans; Epoprostenol; Filtration; Heparin; Humans; Iloprost; Middle Aged; Pulmonary Embolism; Risk Factors; Thrombocytopenia; Thromboembolism; Vena Cava, Inferior; Warfarin