Department of Physiology, University of Alberta, Edmonton, Canada.
Cardiovasc Res. 2011 May 1;90(2):285-94. doi: 10.1093/cvr/cvq363. Epub 2010 Nov 19.
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.
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.
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.
宫内生长受限（IUGR）的成年后代在成年后易患心血管疾病。此外，几种心脏病与心肌能量代谢的变化有关。然而，IUGR 出生对心脏能量代谢的潜在长期影响尚不清楚。本研究旨在评估 IUGR 对有氧条件下和缺血/再灌注（IR）损伤后心脏功能和能量代谢的长期影响。
为了诱导 IUGR，怀孕的 Sprague-Dawley 大鼠从妊娠第 15 天到第 21 天被随机分配到低氧（11.5% O2）或对照（21% O2）环境中。在 4 个月（年轻成年）或 12 个月（衰老）时，使用分离的工作心脏评估雄性和雌性后代对 IR 的敏感性。使用放射性标记的底物评估心脏能量的产生。与对照组相比，IUGR 后代的雄性和雌性都表现出对 IR 损伤的敏感性增加（P<0.05），以及在缺血后质子产生增加（P<0.001），这是由于心肌糖酵解和葡萄糖氧化率之间的不匹配所致。此外，IUGR 出生的后代在再灌注期间表现出乙酰辅酶 A 的心肌产生增加。能量产生与心脏功能之间的不匹配表明，在 IUGR 后代中，再灌注期间的心脏效率相对于对照组降低。
我们的结果表明，缺氧诱导的 IUGR 对 IR 损伤的心脏敏感性具有长期影响，与性别和年龄无关。此外，我们发现葡萄糖代谢存在不匹配，导致 IUGR 出生的后代在缺血后心肌中质子积累，这可能是涉及的潜在机制。
