Epithelial Sodium Channel δ Subunit Is Expressed in Human Arteries and Has Potential Association With Hypertension.

BACKGROUND: Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension. METHODS: Human internal mammary artery (IMA) and aorta were obtained from cardiovascular patients undergoing coronary artery bypass graft surgery. Expression of the ENaC subunit was analyzed by polymerase chain reaction, Western blot, and immunohistochemistry. ENaC function was observed by patch-clamp electrophysiology in endothelial cells isolated from IMA. Levels of ENaC subunit expression levels were compared between arteries from normotensive, uncontrolled hypertensive, and controlled hypertensive patients. RESULTS: For the first time, expression of α, ß, γ, and δ was detected at mRNA and protein levels in human IMA and aorta. Single-channel patch-clamp recordings identified both αßγ- and δßγ-like channel conductance in primary endothelial cells isolated and cultured from IMA. Reduced expression of the δ subunit was observed in controlled hypertensive IMA, whereas reduced expression of γ-ENaC was observed in controlled hypertensive aorta. CONCLUSIONS: These data suggest that functional ENaC channels are expressed in human arteries and their expression levels are associated with hypertension.

Long-chain acylcarnitine 18:1 acutely increases human atrial myocardial contractility and arrhythmia susceptibility.

Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial myocardium. Additionally, we aimed to assess how LCAC 18:1 alters Ca2+ influx and spontaneous Ca2+ release in vitro. Human right atrial trabeculae (n = 32) stimulated at 1 Hz were treated with LCAC 18:1 at a range of concentrations (1-25 µM) for a 45-min period. Exposure to the LCAC induced a dose-dependent positive inotropic effect on myocardial contractility (maximal 1.5-fold increase vs. control). At the 25 µM dose (n = 8), this was paralleled by an enhanced propensity for spontaneous contractions (50% increase). Furthermore, all LCAC 18:1 effects on myocardial function were reversed following LCAC 18:1 washout. In fluo-4-AM-loaded HEK293 cells, LCAC 18:1 dose dependently increased cytosolic Ca2+ influx relative to vehicle controls and the short-chain acylcarnitine C3. In HEK293 cells expressing ryanodine receptor (RyR2), this increased Ca2+ influx was linked to an increased propensity for RyR2-mediated spontaneous Ca2+ release events. Our study is the first to show that LCAC 18:1 directly and acutely alters human myocardial function and in vitro Ca2+ handling. The metabolite promotes proarrhythmic muscle contractions and increases contractility. The exploratory findings in vitro suggest that LCAC 18:1 increases proarrhythmic RyR2-mediated spontaneous Ca2+ release propensity. The direct effects of metabolites on human myocardial function are essential to understand cardiometabolic dysfunction.NEW & NOTEWORTHY For the first time, the fatty acid metabolite, long-chain acylcarnitine 18:1, is shown to acutely increase the arrhythmia susceptibility and contractility of human atrial myocardium. In vitro, this was linked to an influx of Ca2+ and an enhanced propensity for spontaneous RyR2-mediated Ca2+ release.

Short and medium term outcomes of surgery for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: We report one surgeon's experience of corrective surgery for hypertrophic obstructive cardiomyopathy (HOCM) over a 10-year span and comment on factors that influence longer term outcomes. Septal myectomy (SM) and adjunctive procedures, including shortening of the aorta, a novel technique in HOCM patients, are described. METHODS: Perioperative data were obtained by retrospective review of institutional surgical databases between 2001 and 2011. Review of most recent echocardiogram and clinical status by telephone interview was performed. RESULTS: A total of 211 patients underwent SM for HOCM. There was a bimodal age distribution related to sex; mean age for males and females was 46 ± 13 and 54 ± 14 years, respectively (p < 0.001). Functional New York Heart Association (NYHA) class improved significantly after surgery; 79% were in class III-IV preoperatively and 84% were in class I-II at follow-up (p < 0.001). Sixty percent had angina of Canadian Cardiovascular Society (CCS) grade III-IV preoperatively and 89% were in CCS I-II at follow-up (p < 0.001). There were significant improvements in resting left ventricular outflow tract gradient (64 ± 36 to 5 ± 5 mm Hg, p < 0.001), right ventricular systolic pressure (36 ± 7.3 to 32 ± 8 mm Hg, p < 0.001), left atrial size (4.6 ± 0.7 to 4.3 ± 0.6 cm, p < 0.001), and grade of mitral regurgitation (moderate to severe mitral regurgitation 28% to 3.5%, p < 0.001). In-hospital mortality was 0.5%, 1 year survival 98.6%, and 5-year survival 98.1%. Predictors of worse clinical outcomes were preoperative NYHA and CCS class III-IV (p < 0.001, p = 0.05), new onset atrial fibrillation (p < 0.001), and female sex (p = 0.03). CONCLUSIONS: Septal myectomy in patients with obstructive HOCM offers excellent symptom relief and minimal operative risk.

Expanding retrograde saphenous vein graft aneurysm treated with endovascular coiling.

Saphenous vein graft aneurysm is a potentially fatal complication of coronary artery bypass grafting and usually requires surgery. This report describes endovascular coiling of a saphenous vein graft aneurysm that developed after redo coronary artery bypass grafting. The aneurysm occurred in a proximally occluded saphenous vein graft after revascularization of the same target vessel. The procedure required a retrograde approach through a patent left internal mammary and left anterior descending artery to reach and successfully thrombose the aneurysm.