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Rigor and Somnolence: Conceptualizing a Sepsis - Cerebral Connection.
Am J Med
December 2024
Osler Medical Service, Johns Hopkins University School of Medicine, Baltimore, Maryland; Departments of Medicine,, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:
Background: Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger, cyclic guanosine monophosphate (cGMP) leading to increased protein kinase G (PKG) activity and vascular smooth muscle relaxation. NO bioavailability is impaired in inflammatory settings, such as high glucose (HG). We examined whether the direct sGC sensitizer/stimulator vericiguat, augments cGMP production in human vascular smooth muscle cells (HVSMC) exposed to high glucose and explored its effect on vasorelaxation.
View Article and Find Full Text PDFCombination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a "2-Hit" Murine Model.
J Am Heart Assoc
February 2023
Department of Cardiac Surgery Smidt Heart Institute, Cedars-Sinai Medical Center Los Angeles CA.
Article Synopsis
- Recent studies highlight that both excessive and insufficient nitric oxide (NO) production play key roles in heart failure with preserved ejection fraction (HFpEF), raising interest in NO-targeted therapies.
- A mouse model (using high-fat diets and specific treatments) was used to explore the effects of a dual-nitric oxide therapy (sodium nitrite and hydralazine) on heart function and stress levels related to HFpEF.
- The treatment notably improved NO availability and heart function, reduced oxidative stress, and enhanced exercise capacity, suggesting it may effectively mitigate the severity of HFpEF.
Hydrogen Sulfide as a Potential Therapy for Heart Failure-Past, Present, and Future.
Antioxidants (Basel)
March 2021
Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Hydrogen sulfide (HS) is an endogenous, gaseous signaling molecule that plays a critical role in cardiac and vascular biology. HS regulates vascular tone and oxidant defenses and exerts cytoprotective effects in the heart and circulation. Recent studies indicate that HS modulates various components of metabolic syndrome, including obesity and glucose metabolism.
View Article and Find Full Text PDFNovel Göttingen Miniswine Model of Heart Failure With Preserved Ejection Fraction Integrating Multiple Comorbidities.
JACC Basic Transl Sci
February 2021
Cardiovascular Center of Excellence, School of Medicine, Louisiana State University Health Science Center, New Orleans, Louisiana, USA.
A lack of preclinical large animal models of heart failure with preserved ejection fraction (HFpEF) that recapitulate this comorbid-laden syndrome has led to the inability to tease out mechanistic insights and to test novel therapeutic strategies. This study developed a large animal model that integrated multiple comorbid determinants of HFpEF in a miniswine breed that exhibited sensitivity to obesity, metabolic syndrome, and vascular disease with overt clinical signs of heart failure. The combination of a Western diet and 11-deoxycorticosterone acetate salt-induced hypertension in the Göttingen miniswine led to the development of a novel large animal model of HFpEF that exhibited multiorgan involvement and a full spectrum of comorbidities associated with human HFpEF.
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