Chronic Alternate-Day Fasting Results in Reduced Diastolic Compliance and Diminished Systolic Reserve in Rats

被引:26
作者
Ahmet, Ismayil [1 ]
Wan, Ruiqian [2 ]
Mattson, Mark P. [2 ]
Lakatta, Edward G. [1 ]
Talan, Mark I. [1 ]
机构
[1] NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA
[2] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA
关键词
Diastolic dysfunction; heart failure; animal model; nutrition; LEFT ATRIAL VOLUME; CALORIC RESTRICTION; MINERALOCORTICOID RECEPTOR; MYOCARDIAL-INFARCTION; DIETARY RESTRICTION; DISEASE; DYSFUNCTION; IMPROVES; RISK; METABOLISM;
D O I
10.1016/j.cardfail.2010.05.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Based on animal experiments and limited data from the few human trials, alternate-day fasting (ADF) resulted in weight loss, prolonged life, reduced metabolic risk factors for diabetes and cardiovascular diseases, and reduced prevalence of age-related diseases. The present study is the first comprehensive examination of the long-term effects of ADF on general cardiovascular fitness in rats. Methods and Results: Four-month-old male Sprague-Dawley rats were started on ADF or continued on ad libitum diets and followed for 6 months with serial echocardiography. A comprehensive hemodynamic evaluation including a combined dobutamine volume stress test was performed at the end of the study, and hearts were harvested for histological assessment. The 6-month-long ADF diet resulted in a 9% reduction (P<.01) of cardiomyocyte diameter and 3-fold increase in interstitial myocardial fibrosis. Left ventricular chamber size was not affected by ADF and ejection fraction was not reduced, but left atrial diameter was increased 16%, and the ratio of early (E) and late atrial (A) waves, in Doppler-measured mitral flow was reduced (P<.01). Pressure-volume loop analyses revealed a "stiff" heart during diastole in ADF rats, whereas combined dobutamine and volume loading showed a significant reduction in left ventricular diastolic compliance and a lack of increase in systolic pump function, indicating a diminished cardiac reserve. Conclusion: Chronic ADF in rats results in development of diastolic dysfunction with diminished cardiac reserve. ADF is a novel and unique experimental model of diet-induced diastolic dysfunction. The deleterious effect of ADF in rats suggests that additional studies of ADF effects on cardiovascular functions in humans are warranted. (J Cardiac Fail 2010:16:843-853)
引用
收藏
页码:843 / 853
页数:11
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