Efficacy of novel phosphodiesterase inhibitors in rats with monocrotaline-induced pulmonary hypertension

Pulmonary tumour thrombotic microangiopathy (PTTM) and pulmonary tumour emboli (PTE) are distinct but related complications of malignancy. The incidence of each is exceedingly rare, unfortunately often being diagnosed postmortem. Patients with PTTM and PTE typically present with dyspnoea associated with a rapid onset of hypoxia due to pulmonary hypertension (PH), and respiratory failure that is almost certain to be fatal. The prognosis is grim due to the rapidity of the clinical decline and difficulty in establishing an ante-mortem diagnosis. We present a case of new-onset severe PH in a young woman with a recently discovered breast mass. She presented with shortness of breath and experienced rapid deterioration of her cardiopulmonary status which we attributed to PTTM. With early initiation of chemotherapy, systemic steroids and sildenafil, the patient dramatically improved. Case reports have identified early use of steroids, phosphodiesterase inhibitors and other alternative therapies as providing possible benefit in PTTM.

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Pulmonary hypertension in pregnancy

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20210777 ◽

2021 ◽

Vol 10 (3) ◽

pp. 1259

Author(s):

K. Durga ◽

S. Yuvarajan ◽

R. Praveen ◽

Antonious Maria Selvam ◽

Yashoda . ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Phosphodiesterase Inhibitors ◽

High Morbidity ◽

Therapeutic Abortion ◽

Hypertension In Pregnancy ◽

Mean Pulmonary Arterial Pressure ◽

Right Heart Catheterisation ◽

Receptor Blockers ◽

Pulmonary Arterial ◽

In Pregnancy

Pulmonary hypertension is defined as an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest as assessed by right heart catheterisation. Pulmonary hypertension in pregnancy is known to be associated with significantly high morbidity and mortality rate which ranges between 30% and 56%. So during pregnancy, efforts to be made to diagnose common medical ailments that can be complicated by pulmonary hypertension. Bedside 2D Echo and thoracic ultrasound are the strongly recommended in these patients to diagnose early and prevent the devastating complications. Relevant blood investigations need to be sent to diagnose the underlying etiology and to assess the prognosis. Cardiac catheterization is the gold standard investigation of choice for pulmonary hypertension. But it is 1 performed in very few cardiac centres in developing countries. In India diagnosis largely depends on echocardiography. It should be made clear to women at the time of their PAH diagnosis that pregnancy is not recommended due to the high maternal and fetal risks. If a woman with known PHT become pregnant, counselling should be given for therapeutic abortion. If they are willing for therapeutic abortion, it should be done before 22 weeks of gestation. All women with PHT should be initiated on PAH specific therapies (prostanoids, ccbs, phosphodiesterase inhibitors) except endothelin receptor blockers as it is teratogenic. Pregnancy in PAH is difficult to manage and needs mutidisciplanary team. Pregnancy is not recommended in women with PAH and appropriate counselling to be done to the mother and their relatives.

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Targeted Therapy for Pulmonary Hypertension in Premature Infants

Children ◽

10.3390/children7080097 ◽

2020 ◽

Vol 7 (8) ◽

pp. 97

Author(s):

Shannon N. Nees ◽

Erika B. Rosenzweig ◽

Jennifer L. Cohen ◽

Gerson A. Valencia Villeda ◽

Usha S. Krishnan

Keyword(s):

Pulmonary Hypertension ◽

Premature Infants ◽

Phosphodiesterase Inhibitors ◽

Endothelin Receptor Antagonists ◽

Endothelin Receptor ◽

Inhaled Iloprost ◽

Pharmacologic Management ◽

Morbid Conditions ◽

Significant Mortality

Pulmonary hypertension (PH) is common in premature infants with bronchopulmonary dysplasia (BPD) and is associated with significant mortality. Despite expert consensus suggesting the use of targeted therapies such as phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids, there is little data on safety and outcomes in infants with BPD-associated PH (BPD-PH) treated with these medications. We sought to describe the pharmacologic management of BPD-PH and to report outcomes at our institution. Premature infants with BPD-PH born between 2005 and 2016 were included. Follow-up data were obtained through January 2020. A total of 101 patients (61 male, 40 female) were included. Of these, 99 (98.0%) patients were treated with sildenafil, 13 (12.9%) with bosentan, 35 (34.7%) with inhaled iloprost, 12 (11.9%) with intravenous epoprostenol, and nine (8.9%) with subcutaneous treprostinil. A total of 33 (32.7%) patients died during the study period and 10 (9.9%) were secondary to severe to pulmonary hypertension. Of the surviving patients, 57 (83.8%) had follow-up data at a median of 5.1 (range 0.38–12.65) years and 44 (77.2%) were weaned off PH medications at a median 2.0 (range 0–8) years. Mortality for BPD-PH remains high mostly due to co-morbid conditions. However, for those patients that survive to discharge, PH therapies can frequently be discontinued in the first few years of life.

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Phosphodiesterase Inhibitors for Pulmonary Hypertension

New England Journal of Medicine ◽

10.1056/nejmc0912127 ◽

2010 ◽

Vol 362 (6) ◽

pp. 559-560 ◽

Cited By ~ 6

Keyword(s):

Pulmonary Hypertension ◽

Phosphodiesterase Inhibitors

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Prostanoids and Phosphodiesterase Inhibitors in Experimental Pulmonary Hypertension

Current Topics in Developmental Biology ◽

10.1016/s0070-2153(05)67008-1 ◽

2005 ◽

pp. 251-284 ◽

Cited By ~ 6

Author(s):

Ralph Theo Schermuly ◽

Hossein Ardeschir Ghofrani ◽

Norbert Weissmann

Keyword(s):

Pulmonary Hypertension ◽

Phosphodiesterase Inhibitors

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Phosphodiesterase Inhibitors

International Cardiovascular Forum Journal ◽

10.17987/icfj.v17i0.607 ◽

2019 ◽

Vol 17 ◽

Author(s):

Rui Plácido ◽

Mitja Lainscak

Keyword(s):

Clinical Trials ◽

Pulmonary Hypertension ◽

Erectile Dysfunction ◽

Large Scale ◽

Phosphodiesterase Inhibitors ◽

Clinical Role ◽

Definitive Evidence ◽

Phosphodiesterase 3 ◽

Proven Efficacy ◽

Pulmonary Arterial

Phosphodiesterases (PDEs) comprise a superfamily with 11 subfamilies. Within these families, more than 40 isoforms are expressed. Phosphodiesterase-3 inhibitors (PDE3i) are used as inotrope/vasodilators for acute heart failure (HF), and PDE5i for pulmonary hypertension and erectile dysfunction. Despite being studied for chronic HF, none of the PDEis have been presently approved for such an indication itself. The PDE3is milrinone (the PROMISE trial and OPTIME-CHF), raised safety concerns. Although low-dose intravenous milrinone with a beta-blocker is till proposed by some. Enoximone failed to show significant benefits in patients with severe chronic HF in a series of phase 3 clinical trials (ESSENTIAL 1, ESSENTIAL II, EMOTE, EMPOWER). Of the PDE5is, Sildenafil is the most extensively investigated, with proven efficacy in treating erectile dysfunction and pulmonary arterial hypertension, but it has only been tested in relatively small trials in the field of HFrEF, but shows some promise in HFpEF and in pulmonary hypertension complicating HF. Elucidation of the potential clinical role of PDEis on across the spectrum of HF phenotypes will require more definitive evidence from large-scale clinical trials.

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