Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure.

Heart failure (HF) is a leading cause of death and repeated hospitalizations and often involves cardiac mitochondrial dysfunction. However, the underlying mechanisms largely remain elusive. Here, using a mouse model in which myocardial infarction (MI) was induced by coronary artery ligation, we show the metabolic basis of mitochondrial dysfunction in chronic HF. Four weeks after ligation, MI mice showed a significant decrease in myocardial succinyl-CoA levels, and this decrease impaired the mitochondrial oxidative phosphorylation (OXPHOS) capacity. Heme synthesis and ketolysis, and protein levels of several enzymes consuming succinyl-CoA in these events, were increased in MI mice, while enzymes synthesizing succinyl-CoA from α-ketoglutarate and glutamate were also increased. Furthermore, the ADP-specific subunit of succinyl-CoA synthase was reduced, while its GDP-specific subunit was almost unchanged. Administration of 5-aminolevulinic acid, an intermediate in the pathway from succinyl-CoA to heme synthesis, appreciably restored succinyl-CoA levels and OXPHOS capacity and prevented HF progression in MI mice. Previous reports also suggested the presence of succinyl-CoA metabolism abnormalities in cardiac muscles of HF patients. Our results identified that changes in succinyl-CoA usage in different metabolisms of the mitochondrial energy production system is characteristic to chronic HF, and although similar alterations are known to occur in healthy conditions, such as during strenuous exercise, they may often occur irreversibly in chronic HF leading to a decrease in succinyl-CoA. Consequently, nutritional interventions compensating the succinyl-CoA consumption are expected to be promising strategies to treat HF.

Management of Airway Obstruction due to Diffuse Idiopathic Skeletal Hyperostosis in the Cervical Spine: A Case Report and Literature Review.

Diffuse idiopathic skeletal hyperostosis (DISH) is a relatively common progressive noninflammatory entheses disease. Patients are often asymptomatic or are undiagnosed due to minor chronic symptoms. We herein report a rare case in which the primary symptom was sudden-onset upper airway obstruction due to exuberant osteophytosis in the cervical spine. Treatment was successful with careful airway management and surgical osteophyectomy. Most DISH cases in the literature with airway obstruction have been managed with tracheotomy. However, the safety and necessity of this approach remain questionable. We herein discuss the possibility of conservative management as a choice of airway control. Airway obstruction due to DISH may be underrecognized. This highlights the importance of including DISH in the differential diagnosis of airway obstruction. In addition, a detailed evaluation and personalized care for each individual case is essential.