Caloric restriction (CR) extends lifespan and reduces age-associated functional deteriorations in different organs and in many species including mammals. Until recently, cardioprotective actions of caloric restriction have been mainly explained by its beneficial efficacy on progression of arteriosclerosis and changes in lipid profile, while direct myocardial effects have been assumed as neglectible.

Methods: 

Ligation of the left coronary artery or sham operation was performed in young rats. 4 weeks after surgery echocardiography was performed and animals were assigned to different feeding groups (control diet or 40% caloric restriction) as matched pairs according to their left ventricular (LV) function. After 2 months on these diets, LV function, mitochondrial respiratory function, apoptotic activation and cardiometabolic markers (PGC1 alpha, AMPK, Glut-4, adipokines) were investigated.

Results: 

LAD ligation results in a significant decrease in cardiac and mitochondrial function and increases apoptotic cell death. Transient caloric restriction, started 4 weeks after LAD ligation, improves LV and mitochondrial function in postinfarct rats and this is associated with a chronic activation of the AMP-activated protein kinase (AMPK, a2>a1 isoform). The improvement in LV function is also accompanied by a significant reduction in serum BNP (as a prognostic biomarker in heart failure) and a decrease in proapoptotic activation of the myocardium. Inhibition of AMPK (i.p. application of compound C) prevents the improvement in LV function. Similar results were also obtained in alpha 2 AMPK KO mice following LAD ligation and 2 months of CR.

Conclusion: 

The postischemic myocardium is protected from progressive cardiomyocyte loss, progressive heart failure and mitochondrial dysfunction by caloric restriction, started 4 weeks after myocardial infarction. AMPK activation is indispensable for these protective effects of caloric restriction on LV function in the postinfarct rat myocardium.