Comparison of Acute Hemodynamic Effects of Aerosolized Iloprost and Inhaled Nitric Oxide in Adult Congenital Heart Disease with Severe Pulmonary Arterial Hypertension

Zhang, Caojin; Huang, Yigao; Huang, Tao; Huang, Wenhui; Chen, Xia; Huang, Xin-sheng

doi:10.2169/internalmedicine.51.7927

Cited by 8 publications

(11 citation statements)

References 26 publications

(13 reference statements)

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“…In clinical studies, treprostinil showed improvements in exercise capacity, functional class, haemodynamics and survival. Moreover, iloprost inhalation resulted in significant reductions in pulmonary arterial pressure from 110.6 ± 21.8 to 105.5 ± 22.3 mmHg, and increases in pulmonary blood flow from 6.7 ± 3.3 to 9.4 ± 5.8 L·min –1 (Caojin et al ., ). Correlated with our finding, the reduction of the vasodilators in the lungs may be relevant to increased 15‐PGDH expression in pulmonary vascular intima.…”

Section: Discussionmentioning

confidence: 97%

Hypoxia activates 15‐PGDH and its metabolite 15‐KETE to promote pulmonary artery endothelial cells proliferation via ERK1/2 signalling

Liu

Wang

et al. 2014

British J Pharmacology

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Background and Purpose Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15‐hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on the proliferation of pulmonary artery endothelial cells. Experimental Approach We used bromodeoxyuridine incorporation, cell‐cycle analysis, immunohistochemistry and Western blot analysis to study the effects of hypoxia, induced 15‐PGDH) activity and its product, 15‐keto‐6Z, 8Z, 11Z, 13E‐eicosatetraenoic acid (15‐KETE), on endothelial cell proliferation. Scratch‐wound and tube formation assays were also used to study migration of endothelial cells. Key Results 15‐KETE increased DNA synthesis and enhanced the transition from the G0/G1 phase to the S phase in hypoxia. Inhibition of 15‐PGDH or siRNA for 15‐PGDH reversed these effects. 15‐KETE also activated the ERK1/2 signalling pathway. 15‐KETE‐induced cell migration and tube formation were reversed by blocking ERK1/2, but not the p38 MAPK pathway. Conclusions and Implications Hypoxia‐induced endothelial proliferation and migration, an important underlying mechanism contributing to hypoxic pulmonary vascular remodelling, appears to be mediated by 15‐PGDH and 15‐KETE, via the ERK1/2 signalling pathway.

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Section: Discussionmentioning

confidence: 97%

Hypoxia activates 15‐PGDH and its metabolite 15‐KETE to promote pulmonary artery endothelial cells proliferation via ERK1/2 signalling

Liu

Wang

et al. 2014

British J Pharmacology

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“… 56 Some evidence is available supporting tadalafil use in combination with iloprost. 40 Finally, as demonstrated by one randomized study, tadalafil may provide additional benefit when used in combination with ambrisentan in increasing 6MWD and decreasing incidence of clinical worsening. 41 As opposed to bosentan, ambrisentan does not induce CYP3A and would not be expected to decrease tadalafil serum concentrations nor therapeutic efficacy.…”

Section: Clinical Efficacymentioning

confidence: 95%

“…In 2014, results were published from two prospective studies from the People’s Republic of China examining the efficacy of tadalafil when used in various combinations with other PAH treatments. 40 , 41 The first study was a prospective, uncontrolled, open-label evaluation of 47 patients with PAH secondary to congenital heart disease. 40 Patients received a low dose of iloprost administered as 2.5 µg inhaled six times a day for 6 months and then were started on tadalafil 5 mg once daily in combination with iloprost for an additional 6 months.…”

Section: Clinical Efficacymentioning

confidence: 99%

“… 40 , 41 The first study was a prospective, uncontrolled, open-label evaluation of 47 patients with PAH secondary to congenital heart disease. 40 Patients received a low dose of iloprost administered as 2.5 µg inhaled six times a day for 6 months and then were started on tadalafil 5 mg once daily in combination with iloprost for an additional 6 months. Outcome measures included change in 6MWD, Borg dyspnea score, oxygen saturation, WHO functional class, and cardiopulmonary from baseline to 6 months of monotherapy with iloprost.…”

Section: Clinical Efficacymentioning

confidence: 99%

“…Discontinuation rates also remained similar to those rates observed in patients on tadalafil monotherapy. 40 , 41 , 56 In addition to mild-to-moderate AEs, rare but serious AEs associated with tadalafil may occur, including vision loss, hearing loss, and priapism. 21…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

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Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

Henrie¹,

Nawarskas²,

Anderson³

2015

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Pulmonary arterial hypertension (PAH) is a chronic and disabling condition characterized by an elevated pulmonary vascular resistance and an elevated mean pulmonary arterial pressure. Despite recent improvements in treatment availability, PAH remains challenging to treat, burdensome for patients, and ultimately incurable. Tadalafil is a phos-phodiesterase-5 inhibitor that is administered once daily by mouth for the treatment of PAH. Current treatment guidelines recommend tadalafil as an option for patients with World Health Organization functional class II or III PAH. In a placebo-controlled clinical trial, patients taking tadalafil demonstrated significantly improved exercise capacity as measured by the 6-minute walk distance. Patients also experienced decreased incidence of clinical worsening, increased quality of life, and improved cardiopulmonary hemodynamics. Uncontrolled studies and smaller trials have indicated a possible role for tadalafil as a suitable alternative to sildenafil and as a beneficial add-on option when used in combination with other treatments for PAH. Tadalafil is generally safe and well tolerated. Adverse events are typically mild-to-moderate in intensity, and discontinuation rates are usually low. The purpose of this review is to provide an evidence-based evaluation of the clinical utility of tadalafil in the treatment of PAH.

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Safety and tolerability of continuous inhaled iloprost in critically ill pediatric pulmonary hypertension patients: A retrospective case series

Colglazier,

Ng,

Parker

et al. 2023

Pulm. circ.

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Inhaled iloprost (iILO) has shown efficacy in treating patients with hypoxic lung disease and pulmonary hypertension, inducing selective pulmonary vasodilation and improvement in oxygenation. However, its short elimination half‐life of 20–30 min necessitates frequent intermittent dosing (6–9 times per day). Thus, the administration of iILO via continuous nebulization represents an appealing method of drug delivery in the hospital setting. The objectives are: (1) describe our continuous iILO delivery methodology and safety profile in mechanically ventilated pediatric pulmonary hypertension patients; and (2) characterize the initial response of iILO in these pediatric patients currently receiving iNO. Continuous iILO was delivered and well tolerated (median 6 days; range 1–94) via tracheostomy or endotracheal tube using the Aerogen® mesh nebulizer system coupled with a Medfusion® 400 syringe pump. No adverse events or delivery malfunctions were reported. Initiation of iILO resulted in an increase in oxygen saturation from 81.4 ± 8.6 to 90.8 ± 4.1%, p < 0.05. Interestingly, prior iNO therapy for >1 day resulted in a higher response rate to iILO (as defined as a ≥ 4% increase in saturations) compared to those receiving iNO <1 day (85% vs. 50%, p = 0.06). When the use of iILO is considered, continuous delivery represents a safe, less laborious alternative and concurrent treatment with iNO should not be considered a contraindication. However, given the retrospective design and small sample size, this study does not allow the evaluation of the efficacy of continuous iILO on outcomes beyond the initial response. Thus, a prospective study designed to evaluate the efficacy of continuous iILO is necessary.

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Comparison of Acute Hemodynamic Effects of Aerosolized Iloprost and Inhaled Nitric Oxide in Adult Congenital Heart Disease with Severe Pulmonary Arterial Hypertension

Cited by 8 publications

References 26 publications

Hypoxia activates 15‐PGDH and its metabolite 15‐KETE to promote pulmonary artery endothelial cells proliferation via ERK1/2 signalling

Hypoxia activates 15‐PGDH and its metabolite 15‐KETE to promote pulmonary artery endothelial cells proliferation via ERK1/2 signalling

Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

Safety and tolerability of continuous inhaled iloprost in critically ill pediatric pulmonary hypertension patients: A retrospective case series

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