Dalshaug Gregory B, Scholz Thomas D, Smith Oliva M, Bedell Kurt A, Caldarone Christopher A, Segar Jeffrey L
Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1359-69. doi: 10.1152/ajpheart.00686.2001.
To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n = 6 fetuses/group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 +/- 20 vs. 230 +/- 17 ml*min(-1)100 g(-1); LV: 258 +/- 18 vs. 172 +/- 23 mlmin(-1)100 g(-1), both P < 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 +/- 30 to 598 +/- 33 mlmin(-1)*g(-1), P < 0.05) but did not enhance blood flow in 100-day animals (490 +/- 59 to 545 +/- 42 ml*min(-1)*100 g(-1), P > 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls (P < 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.
为了验证冠状动脉血流和冠状动脉血流储备受发育调控这一假说，我们使用荧光微球来研究急性（6小时）肺动脉环扎术（PAB）对两组双胎绵羊胎儿（妊娠100天和128天，足月为145天，每组n = 6只胎儿）右心室（RV）和左心室（LV）的基础血流以及腺苷增强血流的影响。在每组中，一只胎儿接受PAB以将主肺动脉直径缩窄50%，另一只双胎作为未环扎的对照。手术完成6小时后进行生理测量；然后采集组织以分析可能参与冠状动脉血管重塑早期阶段的特定基因。在每个年龄组内，对照胎儿和接受PAB的胎儿之间的动脉血气值、心率和平均动脉血压相似。100天胎儿的两个心室的基础心内膜血流均高于128天胎儿（右心室：341±20 vs. 230±17 ml·min⁻¹·100 g⁻¹；左心室：258±18 vs. 172±23 ml·min⁻¹·100 g⁻¹，均P < 0.05）。在两个年龄组中，对照动物在输注腺苷期间右心室和左心室的心内膜血流均显著增加，且接受PAB的胎儿的心内膜血流高于对照胎儿。PAB后，腺苷使128天胎儿的右心室血流进一步增加（从416±30增至598±33 ml·min⁻¹·g⁻¹，P < 0.05），但未增强100天胎儿的血流（490±59至545±42 ml·min⁻¹·100 g⁻¹，P > 0.2）。在接受PAB的128天而非100天胎儿中，右心室血管内皮生长因子和Flk - 1 mRNA水平相对于对照升高（P < 0.05）。我们得出结论，在绵羊胎儿中，存在以下与发育相关的差异：1）基础心肌血流；2）心肌血流对急性收缩压负荷的适应性反应；3）参与血管生成的特定基因对胎儿心肌负荷增加的反应。
