Sharma Sumeet K, Lucitti Jennifer L, Nordman Cory, Tinney Joseph P, Tobita Kimimasa, Keller Bradley B
Department of Pediatrics, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
Pediatr Res. 2006 Jan;59(1):116-20. doi: 10.1203/01.pdr.0000191579.63339.90. Epub 2005 Dec 2.
Oxygen tension is a critical factor for appropriate embryonic and fetal development. Chronic hypoxia exposure alters cardiovascular (CV) function and structure in the late fetus and newborn, yet the immature myocardium is considered to be less sensitive to hypoxia than the mature heart. We tested the hypothesis that hypoxia during the period of primary CV morphogenesis impairs immature embryonic CV function and embryo growth. We incubated fertile white Leghorn chick embryos in 15% oxygen (hypoxia) or 21% oxygen (control) until Hamburger-Hamilton stage 21 (3.5 d). We assessed in ovo viability and dysmorphic features and then measured ventricular pressure and dimensions and dorsal aortic arterial impedance at stage 21. Chronic hypoxia decreased viability and embryonic wet weight. Chronic hypoxia did not alter heart rate or the ventricular diastolic indices of end-diastolic pressure, maximum ventricular -dP/dt, or tau. Chronic hypoxia decreased maximum ventricular +dP/dt and peak pressure, increased ventricular end-systolic volume, and decreased ventricular ejection fraction, consistent with depressed systolic function. Arterial afterload (peripheral resistance) increased and both dorsal aortic SV and steady-state hydraulic power decreased in response to hypoxia. Thus, reduced oxygen tension during early cardiac development depresses ventricular function, increases ventricular impedance (afterload), delays growth, and decreases embryo survival, suggesting that a critical threshold of oxygen tension is required to support morphogenesis and cardiovascular function in the early embryo.
氧分压是胚胎和胎儿正常发育的关键因素。慢性低氧暴露会改变晚期胎儿和新生儿的心血管（CV）功能及结构，然而未成熟心肌被认为对低氧的敏感性低于成熟心脏。我们检验了这样一个假设，即在主要心血管形态发生期的低氧会损害未成熟胚胎的心血管功能和胚胎生长。我们将可育的白来航鸡胚胎置于15%氧气（低氧）或21%氧气（对照）环境中孵育至汉密尔顿-汉堡分期21期（3.5天）。我们评估了胚胎在卵内的活力和畸形特征，然后在21期测量了心室压力和尺寸以及背主动脉动脉阻抗。慢性低氧降低了活力和胚胎湿重。慢性低氧并未改变心率或心室舒张指标，如舒张末期压力、最大心室 -dP/dt或tau。慢性低氧降低了最大心室 +dP/dt和峰值压力，增加了心室收缩末期容积，并降低了心室射血分数，这与收缩功能受抑制一致。动脉后负荷（外周阻力）增加，并且背主动脉的每搏输出量和稳态水力功率均因低氧而降低。因此，心脏发育早期氧分压降低会抑制心室功能，增加心室阻抗（后负荷），延迟生长，并降低胚胎存活率，这表明早期胚胎的形态发生和心血管功能需要一个关键的氧分压阈值来维持。
