Safety Window for Effective Lesion Crossing in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background: Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension (CTEPH) is limited by a lack of safe and effective tools for crossing these lesions. We aim to identify a safety window for an intraluminal crossing device in this vascular bed by studying the piercing properties of pulmonary arterial vessel walls and intraluminal CTEPH lesion specimens. As a secondary objective, we also describe the histopathologic features of CTEPH lesions. Methods: Specimens were procured from 9 patients undergoing pulmonary endarterectomy. The specimens were subsampled and identified grossly as arterial wall or intraluminal CTEPH lesions. The force needed for tissue penetration was measured using a 0.38-mm (0.015-in) diameter probe in an ex vivo experimental model developed in our lab. Concurrent histology was also performed. Results: The mean force needed to penetrate the arterial wall and intraluminal CTEPH lesions was 1.75 ± 0.10 N (n = 121) and 0.30 ± 0.04 N (n = 56), respectively (P < .001). Histology confirmed the presence of intimal hyperplasia with calcium and hemosiderin deposition in the arterial wall as well as an old, organized thrombus in the lumen. Conclusions: The pulmonary arterial wall is friable and prone to perforation during instrumentation with workhorse coronary guide wires. However, the results of this study demonstrate that a much lower force is needed for the 0.38-mm (0.015-in) probe to penetrate an intraluminal CTEPH lesion compared to pulmonary arterial intima. This finding suggests the existence of a safety window for lesion-crossing devices, enabling effective balloon pulmonary angioplasty.

Pathogenesis, Diagnosis, and Management of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to occur as a sequelae of thromboembolic processes in the pulmonary vasculature. The pathophysiology of CTEPH is multifactorial, including impaired fibrinolysis, endothelial dysregulation, and hypoxic adaptations. The diagnosis of CTEPH is typically delayed considering the nonspecific nature of the symptoms, lack of screening, and relatively low incidence. Diagnostic tools include ventilation-perfusion testing, echocardiography, cardiac catheterization, and pulmonary angiography. The only potentially curative treatment for CTEPH is pulmonary endarterectomy However, approximately 40% of patients are inoperable. Currently, only Riociguat is Food and Drug Administration approved specifically for CTEPH, with additional drug trials underway.

Physiologic, Genomic, and Electrochemical Characterization of Two Heterotrophic Marine Sediment Microbes from the Idiomarina Genus.

Extracellular electron transfer (EET), the process that allows microbes to exchange electrons in a redox capacity with solid interfaces such as minerals or electrodes, has been predominantly described in microbes that use iron during respiration. In this work, we characterize the physiology, genome, and electrochemical properties of two obligately heterotrophic marine microbes that were previously isolated from marine sediment cathode enrichments. Phylogenetic analysis of isolate 16S rRNA genes showed two strains, SN11 and FeN1, belonging to the genus Idiomarina. Strain SN11 was found to be nearly identical to I. loihiensis L2-TRT, and strain FeN1 was most closely related to I. maritima 908087T. Each strain had a relatively small genome (~2.8-2.9 MB). Phenotypic similarities among FeN1, SN11, and the studied strains include being Gram-negative, motile, catalase- and oxidase-positive, and rod-shaped. Physiologically, all strains appeared to exclusively use amino acids as a primary carbon source for growth. This was consistent with genomic observations. Each strain contained 17 to 22 proteins with heme-binding motifs. None of these were predicted to be extracellular, although seven were of unknown localization and lacked functional annotation beyond cytochrome. Despite the lack of homology to known EET pathways, both FeN1 and SN11 were capable of sustained electron uptake over time in an electrochemical system linked to respiration. Given the association of these Idiomarina strains with electro-active biofilms in the environment and their lack of autotrophic capabilities, we predict that EET is used exclusively for respiration in these microbes.

Exercise training after myocardial infarction increases survival but does not prevent adverse left ventricle remodeling and dysfunction in high-fat diet fed mice.

AIMS: Aerobic exercise is an important component of rehabilitation after cardiovascular injuries including myocardial infarction (MI). In human studies, the beneficial effects of exercise after an MI are blunted in patients who are obese or glucose intolerant. Here, we investigated the effects of exercise on MI-induced cardiac dysfunction and remodeling in mice chronically fed a high-fat diet (HFD). MAIN METHODS: C57Bl/6 male mice were fed either a standard (Chow; 21% kcal/fat) or HFD (60% kcal/fat) for 36 weeks. After 24 weeks of diet, the HFD mice were randomly subjected to an MI (MI) or a sham surgery (Sham). Following the MI or sham surgery, a subset of mice were subjected to treadmill exercise. KEY FINDINGS: HFD resulted in obesity and glucose intolerance, and this was not altered by exercise or MI. MI resulted in decreased ejection fraction, increased left ventricle mass, increased end systolic and diastolic diameters, increased cardiac fibrosis, and increased expression of genes involved in cardiac hypertrophy and heart failure in the MI-Sed and MI-Exe mice. Exercise prevented HFD-induced cardiac fibrosis in Sham mice (Sham-Exe) but not in MI-Exe mice. Exercise did, however, reduce post-MI mortality. SIGNIFICANCE: These data indicate that exercise significantly increased survival after MI in a model of diet-induced obesity independent of effects on cardiac function. These data have important translational ramifications because they demonstrate that environmental interventions, including diet, need to be carefully evaluated and taken into consideration to support the effects of exercise in the cardiac rehabilitation of patients who are obese.