Background-Nitrite can be converted to nitric oxide (NO) by a number of different biochemical pathways. In newborn lambs, an aerosol of inhaled nitrite has been found to reduce pulmonary blood pressure, possibly acting via conversion to NO by reaction with intraerythrocytic deoxyhemoglobin. If so, the vasodilating effects of nitrite would be attenuated by free hemoglobin in plasma that would rapidly scavenge NO. Methods and Results-Pulmonary vascular pressures and resistances to flow were measured in anesthetized newborn lambs. Plasma hemoglobin concentrations were then elevated, resulting in marked pulmonary hypertension. This effect was attenuated if infused hemoglobin was first oxidized to methemoglobin, which does not scavenge NO. These results further implicate NO as a tonic pulmonary vasodilator. Next, while free hemoglobin continued to be infused, the lambs were given inhaled NO gas (20 ppm), inhaled sodium nitrite aerosol (0.87 mol/L), or an intravascular nitrite infusion (3 mg/h bolus, 5 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 infusion). Inhaled NO and inhaled nitrite aerosol both resulted in pulmonary vasodilation. Intravascular infusion of nitrite, however, did not. Increases in exhaled NO gas were observed in lambs while breathing the nitrite aerosol (Ϸ20 ppb NO) but not during intravascular infusion of nitrite. Conclusions-We conclude that the pulmonary vasodilating effect of inhaled nitrite results from its conversion to NO in airway and parenchymal lung tissue and is not dependent on reactions with deoxyhemoglobin in the pulmonary circulation. Inhaled nitrite aerosol remains a promising candidate to reduce pulmonary hypertension in clinical application. (Circulation. 2011;123:605-612.)

Support group (SG) participation has been shown to be effective in many chronic medical conditions. The evidence for integrating SG into Pulmonary Hypertension (PH) care and its effect on quality of life (QOL), physical and psychological well-being is limited. Objective: We sought to assess the effect of support group participation on QOL in patients diagnosed with PH and their caregivers. Methods: The emPHasis-10 questionnaire (a tool validated for QOL assessment in PH) was used to evaluate the effect of support group participation. Additional demographic and health-related quality measures were examined. Results: 165 subjects were enrolled in the study; 122 (74.4%) were patients with PH, 41 (25.0%) were their caregivers, and 2 (0.02%) did not respond. The cohort was predominantly female (n=128, 78%), Caucasian (n=10, 61%), and the principal self-reported classification of PH was World Health Organization (WHO) Group 1 (n=85, 51.8%) and the self-reported NYHA Functional Class was II and III (n= 43, 57.3%). Most participants (n=118, 71.5%) attended support groups and of them, a majority (n=107, 90.6%) stated it helped them. There was no difference in QOL as assessed by emPHasis-10 scores with SG participation (median score 30 vs 32, p=0.387). There was self-reported improvement in understanding condition better including procedures such as right heart catheterization, medication compliance and confidence in self-care (p<0.05). Using multivariate logistic regression, baseline variables that were independently associated with emPHasis-10 scores for the entire cohort included knowledge of NYHA-FC (odds ratio 1.919, 95% CI 1.004-3.67, p=0.04) and greater distance traveled to visit PH physician (odds ratio 1.391, 95% CI, p=0.05). Conclusions: Support group participation does not improve quality of life as assessed by emPHasis-10 scores but improves other meaningful health-related quality outcomes.

Tracheal instillation of surfactant to premature newborns improves their survivability but may transiently obstruct airways resulting in undesirable acute effects on cerebral blood flow (CBF) and oxygenation. The acute peridosing hemodynamic effects of surfactant administration may be avoided by minimizing the volume of surfactant administered, but smaller surfactant volumes may also result in less even distribution of surfactant throughout the lung. These experiments were undertaken to compare responses to two surfactants with different dose volumes (porcine-derived poractant alfa, 2.5 mL/kg vs peptide-based synthetic lucinactant, 5.8 mL/kg) given to newly delivered lambs at 85% gestation. Both surfactants resulted in similar improvements in blood gas values, a doubling of dynamic compliance, increases in brain tissue oxygen tension, and stable blood pressure with no significant change in CBF. Distribution of surfactant throughout the lungs was more uniform with lucinactant than poractant alfa when assessed by labeled microspheres. We conclude that improvements in lung mechanics, gas exchange, and changes in CBF are comparable for a porcine-derived and peptide-containing synthetic surfactant, despite instilled volumes differing by 2-fold. Intrapulmonary distribution of surfactant is more uniform after a larger volume is instilled. (Pediatr Res 68: [193][194][195][196][197][198] 2010)

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Chronic hypoxia (CH) is a risk factor in the development of pulmonary hypertension (PH) and recent evidence shows in utero hypoxic stress alters pulmonary structure and function in fetal lambs. Yet, it is unknown whether gestational CH causes pulmonary hypertension in newborn lambs. Reports also indicate Rho‐kinase pathways hold therapeutic promise for the treatment of pulmonary hypertension. Thus, we tested the hypotheses that in utero CH would increase pulmonary arterial pressure (PAP) and that Rho‐kinase inhibition would reduce PH caused by hypoxia. These hypotheses were tested on 12 to 17 day old lambs born at low altitude (LA) or following 100+ days of in utero and postnatal high altitude exposure (HA) at 3801 m. Pulmonary and systemic arterial pressures were measured on anesthetized and ventilated lambs and myography performed on isolated pulmonary arteries (PA). HA did not change baseline PAP, however it significantly augmented hypoxic pulmonary vasoconstriction (HPV). Rho‐kinase inhibition with 2 mg/kg fasudil (intravenous) reduced PAP and blunted HPV in both LA and HA lambs. Rho‐kinase inhibition with 10 μM fasudil or Y27632 also attenuated serotonin mediated PA contractility. Augmentation of HPV in HA lambs and alleviation by fasudil supports the relevance of Rho‐kinase pathways in the treatment of PH in newborns. NIH P01HD031226, R01HD003807 (LDL), R01HL95973 (AB)