Kuo Anderson H, Li Cun, Huber Hillary F, Schwab Matthias, Nathanielsz Peter W, Clarke Geoffrey D
Department of Radiology and Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Department of Animal Science, University of Wyoming, Laramie, WY, USA.
J Physiol. 2017 Jul 1;595(13):4245-4260. doi: 10.1113/JP273928. Epub 2017 May 18.
Maternal nutrient restriction induces intrauterine growth restriction (IUGR) and leads to heightened cardiovascular risks later in life. We report right ventricular (RV) filling and ejection abnormalities in IUGR young adult baboons using cardiac magnetic resonance imaging. Both functional and morphological indicators of poor RV function were seen, many of which were similar to effects of ageing, but also with a few key differences. We observed more pronounced RV changes compared to our previous report of the left ventricle, suggesting there is likely to be a component of isolated RV abnormality in addition to expected haemodynamic sequelae from left ventricular dysfunction. In particular, our findings raise the suspicion of pulmonary hypertension after IUGR. This study establishes that IUGR also leads to impairment of the right ventricle in addition to the left ventricle classically studied.
Maternal nutrient restriction induces intrauterine growth restriction (IUGR), increasing later life chronic disease including cardiovascular dysfunction. Our left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years - human equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long-term LV abnormalities in IUGR offspring. Although it is known that right ventricular (RV) function is dependent on LV health, the IUGR right ventricle remains poorly studied. We examined the right ventricle with cardiac magnetic resonance imaging in the same cohorts. We observed decreased ejection fraction (49 ± 2 vs. 33 ± 3%, P < 0.001), cardiac index (2.73 ± 0.27 vs. 1.89 ± 0.20 l min m , P < 0.05), early filling rate/body surface area (BSA) (109.2 ± 7.8 vs. 44.6 ± 7.3 ml s m , P < 0.001), wall thickening (61 ± 3 vs. 44 ± 5%, P < 0.05), and longitudinal shortening (26 ± 3 vs. 15 ± 2%, P < 0.01) in IUGR animals with increased chamber volumes. Many, but not all, of these changes share similarities to normal older animals. Our findings suggest IUGR-induced pulmonary hypertension should be further investigated and that atrial volume, pulmonic outflow and interventricular septal motion may provide valuable insights into IUGR cardiovascular physiology. Overall, our findings reaffirm that gestational and neonatal challenges can result in long-term programming of poor offspring cardiovascular health. To our knowledge, this is the first study reporting IUGR-induced programmed adult RV dysfunction in an experimental primate model.
母体营养限制会导致宫内生长受限（IUGR），并在以后的生活中增加心血管疾病风险。我们使用心脏磁共振成像报告了IUGR成年幼年狒狒的右心室（RV）充盈和射血异常。观察到右心室功能不佳的功能和形态学指标，其中许多与衰老的影响相似，但也有一些关键差异。与我们之前关于左心室的报告相比，我们观察到右心室的变化更为明显，这表明除了左心室功能障碍预期的血流动力学后遗症外，可能还存在孤立的右心室异常。特别是，我们的发现引发了对IUGR后肺动脉高压的怀疑。这项研究证实，IUGR除了经典研究的左心室之外，还会导致右心室功能受损。
母体营养限制会导致宫内生长受限（IUGR），增加包括心血管功能障碍在内的晚年慢性疾病。我们对IUGR狒狒（8只雄性，8只雌性，5.7岁——相当于人类约25岁）、对照后代（8只雄性，8只雌性，5.6岁）和正常老年（OLD）狒狒（6只雄性，6只雌性，平均15.9岁）进行的左心室（LV）心脏磁共振成像研究显示，IUGR后代存在长期左心室异常。虽然已知右心室（RV）功能依赖于左心室健康，但IUGR右心室的研究仍然很少。我们在同一队列中用心脏磁共振成像检查了右心室。我们观察到IUGR动物的射血分数降低（49±2对33±3%，P<0.001）、心脏指数降低（2.73±0.27对1.89±0.20 l min m，P<0.05）、早期充盈率/体表面积（BSA）降低（109.2±7.8对44.6±7.3 ml s m，P<0.001）、室壁增厚降低（61±3对44±5%，P<0.05）和纵向缩短降低（26±3对15±2%，P<0.01），同时心室容积增加。这些变化中的许多（但不是全部）与正常老年动物相似。我们的研究结果表明，IUGR诱导的肺动脉高压应进一步研究，心房容积、肺动脉流出和室间隔运动可能为IUGR心血管生理学提供有价值的见解。总体而言，我们的研究结果再次证实，妊娠和新生儿期的挑战可导致后代心血管健康长期受损。据我们所知，这是第一项在实验灵长类动物模型中报告IUGR诱导的成年右心室功能障碍的研究。
