Rationale Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked. Objectives We investigated the kinetics of nitrite and S-nitrosothiol-hemoglobin (SNO-Hb) in plasma derived from inhaled NO subjects and how this modifies the cutaneous microvascular response. Findings We enrolled 15 healthy volunteers. Plasma nitrite levels at baseline and during NO inhalation (15 minutes at 40 ppm) were 102 (86–118) and 114 (87–129) nM, respectively. The nitrite peak occurred at 5 minutes of discontinuing NO (131 (104–170) nM). Plasma nitrate levels were not significantly different during the study. SNO-Hb molar ratio levels at baseline and during NO inhalation were 4.7E-3 (2.5E-3–5.8E-3) and 7.8E-3 (4.1E-3-13.0E-3), respectively. Levels of SNO-Hb continued to climb up to the last study time point (30 min: 10.6E-3 (5.3E-3-15.5E-3)). The response to acetylcholine iontophoresis both before and during NO inhalation was inversely associated with the SNO-Hb level (r: -0.57, p = 0.03, and r: -0.54, p = 0.04, respectively). Conclusions Both nitrite and SNO-Hb increase during NO inhalation. Nitrite increases first, followed by a more sustained increase in Hb-SNO. Nitrite and Hb-SNO could be a mobile reservoir of NO with potential implications on the systemic microvasculature.
Patients with pulmonary arterial hypertension (PAH) who are admitted to the hospital pose a challenge to the multidisciplinary healthcare team due to the complexity of the pathophysiology of their disease state and PAH-specific medication considerations. Pulmonary arterial hypertension is a progressive disease that may lead to death as a result of right ventricular (RV) failure. During acute on chronic RV failure it is critical to decrease the pulmonary vascular resistance with the goal of improving RV function and prognosis; therefore, aggressive PAH-treatment based on disease risk stratification is essential. Pulmonary arterial hypertension treatment for acute on chronic RV failure can be impacted by end-organ damage, hemodynamic instability, drug interactions, and PAH medications dosage and delivery. Sotatercept, a first in class activin signaling inhibitor that works on the bone morphogenetic protein/activin pathway is on track for Food and Drug Administration approval for the treatment of PAH based on results of recent trials in where the medication led to clinical and hemodynamic improvements, even when added to traditional PAH-specific therapies. The purpose of this review is to highlight important considerations when starting or continuing sotatercept in patients admitted to the hospital with PAH.
Macrophage migration inhibitory factor (MIF) and 22 a priori selected biomarkers were measured from pulmonary arterial hypertension (PAH) patients. Significant positive correlations were found between MIF and several angiogenic factors suggesting a possible MIF regulation role in PAH angiogenesis and pathobiology, but simultaneously highlighting the biomarkers profiling complexity in PAH.
Pulmonary arterial hypertension (PAH) is a progressive disease, which can be potentially fatal. The management of a complex disease like PAH requires a multidisciplinary approach from a team consisting of physicians, nurses, social workers, and pharmacists. Adherence to PAH-specific therapy is one of the key factors in the management of this disease. Poor adherence to treatment is a common problem in PAH as it is in many chronic diseases. Management of medication interruptions is a challenge in patients with PAH that can lead to negative consequences. However, for most PAH-specific drugs, there are no clear guidelines on how to manage temporary or abrupt medication discontinuations. In this review, we summarized the available literature and provide suggestions on how to manage interruptions of PAH-specific therapies.
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