ABSTRACT
Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.
Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Carvedilol/administration & dosage , Insulin/metabolism , Norepinephrine/metabolism , Obesity/drug therapy , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Administration, Oral , Adrenergic Agents , Animals , Diet, High-Fat/adverse effects , Disease Models, Animal , Glucose/metabolism , Glucose Tolerance Test , Humans , Insulin Resistance , Leptin/blood , Leptin/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice , Norepinephrine/blood , Obesity/etiology , Obesity/metabolism , Signal Transduction/drug effectsABSTRACT
OBJECTIVES: The aim of our work is to investigate the clinical characteristics of coronary artery fistula (CAF) anomalies in South Vietnam. METHODS: This is a retrospective analysis of 119 patients with diagnosis of definite CAF between January 1992 and April 2016. The demographic, clinical, echocardiographic, and angiographic characteristics and management of CAF with short-term outcomes are described. RESULTS: The median age was 15 years (range, 1-79 years), with 49 male (41%) and 70 female (59%). There were 77 symptomatic patients (64.7%) and 91 patients (76.5%) who presented with a murmur. The electrocardiogram was abnormal in 45.4% and cardiac enlargement or increased pulmonary vasculature were seen in 76 patients (63.9%) on chest X-ray. The sensitivity of echocardiography for CAF diagnosis was 79%. The source of the fistula was most often from the RCA (54%), most commonly to right atrium (34.5%) or right ventricle (31.1%). In comparison with surgery, transcatheter closure had a shorter hospital length of stay (5.4 ± 3.8 days vs 12.6 ± 6.5 days, P = .02) and better postprocedural left ventricular ejection fraction (67.9 ± 8.1% vs 62.9 ± 6.0%, P = .03). CONCLUSION: The majority of fistula in this study originated from the RCA and terminated in the right atrium or the right ventricle. Transcatheter and surgical closure are both relatively safe and effective, with the potential for shortened length of hospital stay following transcatheter closure.