Long-term effects of intrauterine growth restriction on cardiac metabolism and susceptibility to ischaemia/reperfusion.

AIMS Adult offspring who are born intrauterine growth restricted (IUGR) are at risk of developing cardiovascular diseases during adulthood. Additionally, several cardiac diseases are associated with changes in myocardial energy metabolism. However, the potential long-term effects of being born IUGR on cardiac energetics are unknown. The aim of this study was to assess the long-term effect of IUGR on cardiac performance and energy metabolism under aerobic conditions and after ischaemia/reperfusion (IR) injury. METHODS AND RESULTS To induce IUGR, pregnant Sprague-Dawley rats were randomly assigned to hypoxic (11.5% O(2)) or control (21% O(2)) environments from day 15 to 21 of pregnancy. Cardiac susceptibility to IR was evaluated in male and female offspring at 4 (young-adult) or 12 (ageing) months of age using isolated working hearts. Cardiac production of energy was evaluated using radiolabelled substrates. Both male and female IUGR offspring exhibited an increased susceptibility to IR injury compared with controls (P< 0.05) as well as an increased post-ischaemic production of protons (P< 0.001) secondary to a mismatch between myocardial glycolysis and glucose oxidation rates. Moreover, offspring born IUGR exhibited an increased myocardial production of acetyl-CoA during reperfusion. The mismatch between energy production and cardiac performance indicates that in IUGR offspring, cardiac efficiency during reperfusion was decreased relative to controls. CONCLUSION Our results suggest that hypoxia-induced IUGR has long-term effects on cardiac susceptibility to IR injury that are independent of sex and age. Moreover, we identified a mismatch in glucose metabolism, leading to proton accumulation in the post-ischaemic myocardium of offspring born IUGR as a potential mechanism involved.