Chronic alternate-day fasting results in reduced diastolic compliance and diminished systolic reserve in rats

Ismayil Ahmet, Ruiqian Wan, Mark P. Mattson, Edward G. Lakatta, Mark I. Talan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)843-853
Number of pages11
JournalJournal of cardiac failure
Volume16
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Diastolic dysfunction
  • animal model
  • heart failure
  • nutrition

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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