酮体
酮症
医学
心力衰竭
射血分数
内科学
内分泌学
动物研究
新陈代谢
糖尿病
作者
Senthil Selvaraj,Daniel P. Kelly,Kenneth B. Margulies
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2020-06-02
卷期号:141 (22): 1800-1812
被引量:119
标识
DOI:10.1161/circulationaha.119.045033
摘要
Despite existing therapy, patients with heart failure (HF) experience substantial morbidity and mortality, highlighting the urgent need to identify novel pathophysiological mechanisms and therapies, as well. Traditional models for pharmacological intervention have targeted neurohormonal axes and hemodynamic disturbances in HF. However, several studies have now highlighted the potential for ketone metabolic modulation as a promising treatment paradigm. During the pathophysiological progression of HF, the failing heart reduces fatty acid and glucose oxidation, with associated increases in ketone metabolism. Recent studies indicate that enhanced myocardial ketone use is adaptive in HF, and limited data demonstrate beneficial effects of exogenous ketone therapy in studies of animal models and humans with HF. This review will summarize current evidence supporting a salutary role for ketones in HF including (1) normal myocardial ketone use, (2) alterations in ketone metabolism in the failing heart, (3) effects of therapeutic ketosis in animals and humans with HF, and (4) the potential significance of ketosis associated with sodium-glucose cotransporter 2 inhibitors. Although a number of important questions remain regarding the use of therapeutic ketosis and mechanism of action in HF, current evidence suggests potential benefit, in particular, in HF with reduced ejection fraction, with theoretical rationale for its use in HF with preserved ejection fraction. Although it is early in its study and development, therapeutic ketosis across the spectrum of HF holds significant promise.
科研通智能强力驱动
Strongly Powered by AbleSci AI