Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents.
Ontology highlight
ABSTRACT:
SUBMITTER: Porta NF
PROVIDER: S-EPMC3562500 | biostudies-literature | 2012 Mar
REPOSITORIES: biostudies-literature
Publications
Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents.
Porta Nicolas F M NF Steinhorn Robin H RH
Clinics in perinatology 20120301 1
The perinatal transition from fetal to extrauterine life requires a dramatic change in the circulatory pattern as the organ of gas exchange switches from the placenta to the lungs. Pulmonary hypertension can occur during early newborn life, and present as early respiratory failure or as a complication of more chronic diseases, such as bronchopulmonary dysplasia. The most effective pharmacotherapeutic strategies for infants with persistent pulmonary hypertension of the newborn are directed at sel ...[more]
Similar Datasets
Project description:Vasoreactivity testing with inhaled NO is recommended for pulmonary arterial hypertension (PAH) because of its therapeutic and prognostic value. Sildenafil has acute pulmonary vasodilating properties, but its diagnostic and prognostic impact in PAH is unknown. Our objective was to compare acute vasodilating responses to sildenafil and those to NO during right heart catheterization and also their prognostic values in patients with PAH. Ninety-nine patients with idiopathic PAH and 99 with associated PAH underwent vasoreactivity testing with NO and sildenafil. Only mild adverse effects of sildenafil, in the form of hypotension, were observed, at a rate of 4.5%. The acute responder rate was 8.1% for NO and 11.6% for sildenafil. The NO-induced response in mean pulmonary arterial pressure and cardiac output correlated with the response to sildenafil. Thirteen patients were long-term responders to calcium channel blockers (CCBs), and 3 of them were correctly identified by acute vasoreactivity test with both drugs. The specificity of the vasoreactivity test for identifying long-term CCB responders was 88.9% for NO and 85.1% for sildenafil testing. A trend toward better survival was found in sildenafil and NO responders, compared with nonresponders. Use of sildenafil for vasoreactivity testing is safe. Sildenafil may be useful as alternative vasoreactivity-testing agent, identifying the same number of long-term CCB responders as NO. However, NO seems to be a more ideal testing drug because of its pharmacologic properties. Moreover, sildenafil vasoreactivity testing might contribute to an improved estimate of prognosis among patients with PAH.
| S-EPMC4449241 | biostudies-other
Project description:PurposeInhaled nitric oxide (iNO) selectively vasodilates the pulmonary circulation but the effects are sometimes insufficient. Available intravenous (iv) substances are non-selective and cause systemic side effects. The pulmonary and systemic effects of iNO and an iv mono-organic nitrite (PDNO) were compared in porcine models of acute pulmonary hypertension.MethodsIn anesthetized piglets, dose-response experiments of iv PDNO at normal pulmonary arterial pressure (n=10) were executed. Dose-response experiments of iv PDNO (n=6) and iNO (n=7) were performed during pharmacologically induced pulmonary hypertension (U46619 iv). The effects of iv PDNO and iNO were also explored in 5 mins of hypoxia-induced increase in pulmonary pressure (n=2-4).ResultsPDNO (15, 30, 45 and 60 nmol NO kg-1 min-1 iv) and iNO (5, 10, 20 and 40 ppm which corresponded to 56, 112, 227, 449 nmol NO kg-1 min-1, respectively) significantly decreased the U46619-increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) to a similar degree without significant decreases in mean arterial pressure (MAP) or systemic vascular resistance (SVR). iNO caused increased levels of methemoglobin. At an equivalent delivered NO quantity (iNO 5 ppm and PDNO 45 nmol kg-1 min-1 iv), PDNO decreased PVR and SVR significantly more than iNO. Both drugs counteracted hypoxia-induced pulmonary vasoconstriction and they decreased the ratio of PVR and SVR in both settings.ConclusionIntravenous PDNO was a more potent pulmonary vasodilator than iNO in pulmonary hypertension, with no severe side effects. Hence, this study supports the potential of iv PDNO in the treatment of acute pulmonary hypertension.
| S-EPMC7034972 | biostudies-literature
Project description:IntroductionSevere chronic obstructive pulmonary disease (COPD) is often associated with secondary pulmonary hypertension (PH), which worsens prognosis. PH can be lowered by oxygen, but also by inhaled nitric oxide (NO), which has the potential to improve the health status of these patients. NO is an important mediator in vascular reactions in the pulmonary circulation. Oral compounds can act through NO-mediated pathways, but delivering pulsed inhaled NO (iNO) directly to the airways and pulmonary vasculature could equally benefit patients. Therefore, a proof-of-concept study was performed to quantify pulmonary blood vessel caliber changes after iNO administration using computed tomography (CT)-based functional respiratory imaging (FRI).MethodsSix patients with secondary PH due to COPD received "pulsed" iNO in combination with oxygen for 20 minutes via a nasal cannula. Patients underwent a high-resolution CT scan with contrast before and after iNO. Using FRI, changes in volumes of blood vessels and associated lobes were quantified. Oxygen saturation and blood pressure were monitored and patients were asked about their subjective feelings.ResultsPulmonary blood vessel volume increased by 7.06%±5.37% after iNO. A strong correlation (Ω(2) 0=0.32, P=0.002) was obtained between ventilation and observed vasodilation, suggesting that using the pulsed system, iNO is directed toward the ventilated zones, which consequently experience more vasodilation. Patients did not develop oxygen desaturation, remained normotensive, and perceived an improvement in their dyspnea sensation.ConclusionInhalation of pulsed NO with oxygen causes vasodilation in the pulmonary circulation of COPD patients, mainly in the well-ventilated areas. A high degree of heterogeneity was found in the level of vasodilation. Patients tend to feel better after the treatment. Chronic use trials are warranted.
| S-EPMC4940019 | biostudies-literature
Project description:BackgroundThe aim of this study was to examine the action of inhaled nitric oxide in the patients with pulmonary hypertension administered with a face mask before anesthesia induction.MethodsTen adult patients scheduled for heart surgery with sternotomy were included in this prospective, interventional, single centre study. The inclusion criteria were patients scheduled for heart surgery with sternotomy with cardiopulmonary bypass (CPB), aged >18 years which presents a pulmonary hypertension (PH) (class 2 or 3 according to the Dana Point classification) with systolic pulmonary arterial pressure (PAPS) >40 mmHg diagnosed by preoperative right cardiac catheterization or by transthoracic echocardiography. The exclusion criteria were: heart transplant, PH of type 1, 4, 5, according to the Dana Point classification, methemoglobin reductase deficit, incapacity to understand the protocol and sign the consent.ResultsThe administration of iNO decrease pulmonary hypertension (P < 0,001 compared to room air; P = 0,01 compared to pure oxygen administration). The iNO administration did not improve arterial blood oxygenation. The hyperoxia, decrease the cardiac index even with right ventricular post charge decrease. The increased blood oxygenation content cause systemic vascular vasoconstriction and decrease the peripheral oxygen extraction showed with VO2 linear increase (P < 0,001).ConclusionsThe administration of inhaled nitric oxide with a face mask before anaesthesia induction is safe and effective method to reduce pulmonary hypertension. The oxygen and hyperoxia influences the systemic vascular resistance and peripheral oxygen consumption.
| S-EPMC8617383 | biostudies-literature
Project description:The global COVID-19 pandemic has become the largest public health challenge of recent years. The incidence of COVID-19-related acute hypoxemic respiratory failure (AHRF) occurs in up to 15% of hospitalized patients. Antiviral drugs currently available to clinicians have little to no effect on mortality, length of in-hospital stay, the need for mechanical ventilation, or long-term effects. Inhaled nitric oxide (iNO) administration is a promising new non-standard approach to directly treat viral burden while enhancing oxygenation. Along with its putative antiviral affect in COVID-19 patients, iNO can reduce inflammatory cell-mediated lung injury by inhibiting neutrophil activation, lowering pulmonary vascular resistance and decreasing edema in the alveolar spaces, collectively enhancing ventilation/perfusion matching. This narrative review article presents recent literature on the iNO therapy use for COVID-19 patients. The authors suggest that early administration of the iNO therapy may be a safe and promising approach for the treatment of COVID-19 patients. The authors also discuss unconventional approaches to treatment, continuous versus intermittent high-dose iNO therapy, timing of initiation of therapy (early versus late), and novel delivery systems. Future laboratory and clinical research is required to define the role of iNO as an adjunct therapy against bacterial, viral, and fungal infections.
| S-EPMC8962307 | biostudies-literature
Project description:The purpose of this study is to comprehensively elucidate the role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema using cap analysis of gene expression (CAGE) sequencing.
2021-01-18 | GSE164521 | GEO
Project description:Currently, there are no approved treatments for infants with acute bronchiolitis, the leading cause for hospitalization of infants worldwide, and thus the recommended approach is supportive. Inhaled Nitric oxide (iNO), possesses anti-viral properties, improves oxygenation, and was shown to be safe in infants with respiratory conditions. Hospitalized infants with acute bronchiolitis were therefore recruited to a prospective double-blinded, multi-center, randomized controlled pilot study. They received intermittent high dose iNO (160 ppm) plus oxygen/air for 30 min or oxygen/air alone (control), five times/day, up to 5 days. Sixty-nine infants were enrolled. No difference was observed in frequencies of subjects with at least one Adverse Event (AE) in iNO (44.1%) vs. control (55.9%); neither was Methemoglobin >7% safety threshold. No drug-related serious AEs (SAEs) were reported. Analysis of Per-Protocol population revealed that length of stay (LOS), time to SpO2 ≥92%, and time to mTal clinical score ≤5 improved by 26.7 ± 12.7 (Welch's t-test p = 0.04), 20.8 ± 8.9 (p = 0.023), and 14.6 ± 9.1 (p = 0.118) hours, respectively, in the iNO group compared to the control. Overall, high dose iNO (160ppm) was safe, well-tolerated, reduced LOS and showed rapid improvement of oxygen saturation, compared to the standard therapy. Further investigation in larger cohorts is warranted to validate these encouraging efficacy outcomes. (Trial registration: NCT03053388).
| S-EPMC7295966 | biostudies-literature
Project description:OBJECTIVE:To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. METHODS:This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50?parts per million nitrogen (placebo) or oxygen plus 50?ppm NO for 24?h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14?pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90?pg/mL and a Borg dyspnea score???2. The sample size of N?=?76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha?=?5%. RESULTS:We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24?h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P?=?0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P?=?0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24?h (P?=?0.010, Cochrane's Q test). CONCLUSIONS:In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography. CLINICAL TRIAL REGISTRATION:NCT01939301.
| S-EPMC7047892 | biostudies-literature
Project description:The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J'awNO) and the distal airway/alveolar concentration of NO (CANO). We recruited 24 patients with COPD and performed FENO analysis at multiple expiratory flows before and after treatment with inhaled ?2-agonist bronchodilator therapy. For the 21 patients analysed, FENO50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7-3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FENO50 correlated positively with the change in J'awNO (rs = 0.67, P < 0.001; rs = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FENO analysis in COPD patients should therefore be considered in both research and clinical settings.
| S-EPMC4892672 | biostudies-literature
Project description:BackgroundThe study hypothesis is that administration of inhaled nitric oxide (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve right ventricular (RV) systolic function and reduce RV strain and necrosis, while improving patient dyspnea, more than treatment with oxygen alone.MethodsThis article describes the rationale and protocol for a registered (NCT01939301), nearly completed phase II, 3-center, randomized, double-blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, and have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 hours) with blood sampling before and after treatment, and mandatory echocardiography and high-sensitivity troponin posttreatment to assess the composite primary end point. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high-sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=.05 and β=.20. Safety was ensured by continuous spectrophotometric monitoring of percentage of methemoglobinemia and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software, and physical shielding of the device display and query of the clinical care team to assess blinding efficacy.ResultsWe have enrolled 78 patients over a 31-month period. No patient has been withdrawn as a result of a safety concern, and no patient has had a serious adverse event related to NO.ConclusionsWe present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE.
| S-EPMC5412723 | biostudies-literature