What is the clinical evidence from this study?

Study design: Other. Population: Failing, postinfarct myocardium. Intervention: Caloric restriction vs. Control diet. Primary outcome: Left ventricular function.

March 16, 2022Open Access

AMPK Activation Is Indispensable for the Protective Effects of Caloric Restriction on Left Ventricular Function in Postinfarct Myocardium

Key Result

Caloric restriction significantly improved left ventricular function in postinfarct rats and mice compared to control diet, and this protective effect was prevented by AMPK inhibition or loss.

Structured PICO

Does caloric restriction improve left ventricular function in postinfarct myocardium, and is AMPK activation indispensable for these effects?

Population

Rats and mice with failing, postinfarct myocardium assigned to 40% caloric restriction or control diet for 8 weeks.

Intervention

40% caloric restriction (CR) for 8 weeks, with or without AMPK inhibitor (in rats) or alpha 2 AMPK knock-out (in mice)

Comparator

Control diet

Outcome

Left ventricular (LV) function analyzed by echocardiographysurrogate

Caloric restriction protects the failing, postischemic heart from progressive loss of LV systolic function, an effect that is dependent on AMPK activation.

Abstract

BACKGROUND: Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury. Here, we investigated the role of AMP-activated protein kinase (AMPK) in mediating the cardioprotective CR effects in failing, postinfarct myocardium. METHODS: Ligation of the left coronary artery or sham operation was performed in rats and mice. Four weeks after surgery, left ventricular (LV) function was analyzed by echocardiography, and animals were assigned to different feeding groups (control diet or 40% CR, 8 weeks) as matched pairs. The role of AMPK was investigated with an AMPK inhibitor in rats or the use of alpha 2 AMPK knock-out mice. RESULTS: CR resulted in a significant improvement in LV function, compared to postinfarct animals receiving control diet in both species. The improvement in LV function was accompanied by a reduction in serum BNP, decrease in LV proapoptotic activation, and increase in mitochondrial biogenesis in the LV. Inhibition or loss of AMPK prevented most of these changes. CONCLUSIONS: The failing, postischemic heart is protected from progressive loss of LV systolic function by CR. AMPK activation is indispensable for these protective effects.

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