Pulmonary hypertension (PH) represents a group of disorders characterized by elevated mean pulmonary artery (PA) pressure, progressive right ventricular failure, and often death. Some of the hallmarks of pulmonary hypertension include endothelial dysfunction, intimal and medial proliferation, vasoconstriction, inflammatory infiltration, and in situ thrombosis. The vascular remodeling seen in pulmonary hypertension has been previously linked to the hyperproliferation of PA smooth muscle cells. This excess proliferation of PA smooth muscle cells has recently been associated with changes in metabolism and mitochondrial biology, including changes in glycolysis, redox homeostasis, and mitochondrial quality control. In this review, we summarize the molecular mechanisms that have been reported to contribute to mitochondrial dysfunction, metabolic changes, and redox biology in PH.

Pulmonary hypertension (PH) is a progressive disease marked by pulmonary vascular remodeling and right ventricular failure. Inflammation and oxidative stress are critical in PH pathogenesis, with early pulmonary vascular inflammation preceding vascular remodeling. Extracellular superoxide dismutase (EC-SOD), a key vascular antioxidant enzyme, mitigates oxidative stress and protects against inflammation and fibrosis in diverse lung and vascular disease models. This study utilizes a murine hypobaric hypoxia model to investigate the role of lung EC-SOD on hypoxia-induced platelet activation and platelet lung accumulation, a critical factor in PH-related inflammation. We found that lung EC-SOD overexpression blocked hypoxia-induced platelet activation and platelet accumulation in the lung. Though lung EC-SOD overexpression increased lung EC-SOD content, it did not impact plasma extracellular SOD activity. However, ex vivo, exogenous extracellular SOD treatment specifically blunted convulxin-induced platelet activation but did not blunt platelet activation with thrombin or ADP. Our data identify platelets as a novel target of EC-SOD in response to hypoxia, providing a foundation to advance the understanding of dysregulated redox signaling and platelet activation in PH and other chronic hypoxic lung diseases.

Introduction: Etomidate is commonly used for induction of anesthesia for rapid sequence intubation (RSI). It has little impact on hemodynamic status, making it a widely used agent. Due to the inhibition of cortisol production, etomidate causes adrenal suppression. The purpose of this study is to determine whether there is a correlation with etomidate use and the incidence of secondary infections. Methods: This was a retrospective cohort of hospitalized patients who received either etomidate or control (ketamine, propofol, or no agent) for RSI. The primary endpoint was the incidence of secondary infections. Secondary outcomes included number of mechanical ventilator-free days within 28 days, 30-day mortality, length of hospital stay, and length of intensive care unit stay. Results: A total of 434 patients were reviewed, of which 129 (29.7%) met the study criteria (n = 94 etomidate; n = 35 control). The incidence of secondary infection was numerically higher in the etomidate group compared with the control group, though this was not statistically significant (38.7% vs. 28.6%, p = 0.447). Also, though the secondary outcomes showed no statistically significant difference between the groups, the patients in the control group had a longer hospital stay (14.0 vs. 18.1, p = 0.20) and a longer ICU stay (11.0 vs. 14.1, p = 030). Furthermore, the etomidate group had a non-statistically significant higher incidence of bacteremia (8 vs. 0, p = 0.17) Conclusion: The use of etomidate was not associated with increased incidence of secondary infection. To fully understand the effects of etomidate use and its subsequent adrenal suppression, larger studies are needed.