What is the clinical evidence from this study?

Study design: Other. Population: Aged myocardium (n=40). Intervention: Caloric restriction vs. Beta-blocker, diuretic, or control diet. Primary outcome: Change in Left Ventricular Ejection Fraction (LVEF) (9.2 ± 1.5% increase, p=<0.05).

January 21, 2021Open Access

Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium

Q: What are the key findings of this study?

Caloric restriction reduced sympathetic activity similarly to beta-blockers but provided additional mitochondrio-protective effects and improved left ventricular ejection fraction by 9.2% in aged rats.

Key Result

Caloric restriction reduced sympathetic activity similarly to beta-blockers but provided additional mitochondrio-protective effects and improved left ventricular ejection fraction by 9.2% in aged rats.

Structured PICO

Does caloric restriction improve cardiac function and mitochondrial biogenesis compared to beta-blockers or diuretics in aged Wistar rats?

Population

40 male 18-month-old Wistar rats were randomized to caloric restriction, beta-blocker, diuretic, or control diet for 3 months to evaluate cardiac function and mitochondrial protection.

Intervention

Caloric restriction (-40% kcal) for 3 months

Comparator

Beta-blocker therapy, diuretic medication (furosemide), or control diet

Outcome

Cardiac function, activated signalling cascades, markers of apoptosis, and mitochondrial biogenesissurrogate

Caloric restriction achieves protective effects on mitochondria and improves left ventricular function in aged hearts beyond the reduction of sympathetic activity seen with beta-blockers.

Main Result

Effect estimate: 9.2 ± 1.5% increase

p-value: p=<0.05

Limitations

Caloric restriction represents a multifactorial intervention potentially harmful in patients or animals with CHF accompanied by cardiac cachexia.
Severe caloric restriction may mediate direct negative effects such as endothelial dysfunction and cardiac arrhythmia.
Lack of controlled trials on the effects of long-term caloric restriction on cardiac function in senescent humans.

Abstract

Increased activation of sympathetic nervous system contributes to congestive heart failure (CHF) progression, and inhibition of sympathetic overactivation by beta-blockers is successful in CHF patients. Similarly, caloric restriction (CR) reduces sympathetic activity but mediates additional effects. Here, we compared the cardiac effects of CR (- 40% kcal, 3 months) with beta-blocker therapy (BB), diuretic medication (DF) or control diet in 18-months-old Wistar rats. We continuously recorded blood pressure, heart rate, body temperature and activity with telemetric devices and analysed cardiac function, activated signalling cascades and markers of apoptosis and mitochondrial biogenesis. During our study, left ventricular (LV) systolic function improved markedly (CR), mildly (BB) or even deteriorated (DF; control). Diastolic function was preserved by CR and BB but impaired by DF. CR reduced blood pressure identical to DF and BB and heart rate identical to BB. Plasma noradrenaline was decreased by CR and BB but increased by DF. Only CR reduced LV oxidative damage and apoptosis, induced AMPK and Akt phosphorylation and increased mitochondrial biogenesis. Thus, additive to the reduction of sympathetic activity, CR achieves protective effects on mitochondria and improves LV function and ROS damage in aged hearts. CR mechanisms may provide additional therapeutic targets compared to traditional CHF therapy.

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