Division of Cardiovascular Surgery, Montréal Children's Hospital-McGill University Health Centre, Canada.
Int J Cardiol. 2012 Apr 19;156(2):165-73. doi: 10.1016/j.ijcard.2010.10.135. Epub 2010 Dec 4.
There is a growing population of adults with repaired cyanotic congenital heart disease. These patients have increased risk of impaired cardiac health and premature death. We hypothesized that hypoxia in early life before surgical intervention causes lasting changes in left ventricular structure and function with physiological implications in later life.
Sprague-Dawley rats reared initially hypoxic conditions (FiO(2)=0.12) for days 1-10 of life were compared to rats reared only in ambient air. Cellular morphology and viability were compared among LV cardiomyocytes and histological analyses were performed on LV myocardium and arterioles. Intracellular calcium transients and cell shortening were measured in freshly-isolated cardiomyocytes, and mitochondrial hexokinase 2 (HK2) expression and activity were determined. Transthoracic echocardiography was used to assess LV function in anesthetized animals.
Cardiomyocytes from adult animals following hypoxia in early life had greater cellular volumes but significantly reduced viability. Echocardiographic analyses revealed LV hypertrophy and diastolic dysfunction, and alterations in cardiomyocyte calcium transients and cell shortening suggested impaired diastolic calcium reuptake. Histological analyses revealed significantly greater intima-media thickness and decreased lumen area in LV arterioles from hypoxic animals. Alterations in mitochondrial HK2 protein distribution and activity were also observed which may contribute to cardiomyocyte fragility.
Hypoxia in early life causes lasting changes in left ventricular structure and function that may negatively influence myocardial and vascular responses to physiological stress in later life. These data have implications for the growing population of adults with repaired or palliated cyanotic congenital heart disease.
患有修复后紫绀型先天性心脏病的成年人数量不断增加。这些患者心脏健康受损和早逝的风险增加。我们假设，在手术干预之前的生命早期的缺氧会导致左心室结构和功能的持久变化，对以后的生活产生生理影响。
比较了在生命的头 10 天中最初处于低氧条件（FiO（2）= 0.12）的 Sprague-Dawley 大鼠和仅在环境空气中生长的大鼠。比较了 LV 心肌细胞中的细胞形态和活力，并对 LV 心肌和小动脉进行了组织学分析。在新鲜分离的心肌细胞中测量了细胞内钙瞬变和细胞缩短，并测定了线粒体己糖激酶 2（HK2）的表达和活性。使用经胸超声心动图评估麻醉动物的 LV 功能。
早期生活中缺氧的成年动物的心肌细胞具有更大的细胞体积，但活力明显降低。超声心动图分析显示 LV 肥大和舒张功能障碍，并且心肌细胞钙瞬变和细胞缩短的改变表明舒张钙再摄取受损。组织学分析显示，来自低氧动物的 LV 小动脉的内中膜厚度明显增加，管腔面积减小。还观察到线粒体 HK2 蛋白分布和活性的改变，这可能导致心肌细胞脆弱。
生命早期的缺氧会导致左心室结构和功能的持久变化，这可能会对以后生活中心肌和血管对生理应激的反应产生负面影响。这些数据对于患有修复或姑息性紫绀型先天性心脏病的成年人数不断增加具有重要意义。
