Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

Abstract

. Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts. Am J Physiol Heart Circ Physiol 282: H1359-H1369, 2002. First published December 6, 2001 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 ϭ 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 Ϯ 20 vs. 230 Ϯ 17 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ; LV: 258 Ϯ 18 vs. 172 Ϯ 23 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , both P Ͻ 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 Ϯ 30 to 598 Ϯ 33 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , P Ͻ 0.05) but did not enhance blood flow in 100-day animals (490 Ϯ 59 to 545 Ϯ 42 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , P Ͼ 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls (P Ͻ 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.hypertrophy; vascular endothelial growth factor; angiogenesis IN THE ADULT, adaptive growth of the heart in response to hypertrophic stimuli involves functional and morphological changes that are predictable depending on the stimuli (32, 33). Concomitant with the development of cardiac hypertrophy in the adult are qualitative and quantitative changes in gene expression, including upregulation of the so-called fetal cardiac genes, including ␤-myosin heavy chain, ␣-actin, and atrial natriuretic factor, and a reversion to fetal metabolic pathways for energy production (1,32,33,43). In the fetal heart, however, the molecular triggers for increasing ventricular mass in response to increased load are poorly understood and may be quite different from those in the adult, particularly given the ability of the fetal heart to increase mass by both hypertrop...

Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep

“…Myocardial blood flow was determined with fluorescent microspheres, as described previously (8). Briefly, for each blood flow determination, ϳ1.2 ϫ 10 6 15 m fluorescent-labeled polystyrene 10 microspheres (Triton Technology, San Diego, CA), suspended in 1 ml of 0.9% NaCl with 0.02% Tween 20 and 0.02% thimersol, were injected into the left atrium and flushed with 2 ml of 0.9% NaCl over a 30-s period.…”

“…Beginning 25 s before the microsphere injection, reference blood samples were withdrawn from the carotid catheter (tip in the ascending aorta) into heparinized glass syringes for 2.5 min at a rate of 2 ml/min. After a 15-min recovery period, a continuous left atrial infusion of adenosine (150 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was started to achieve maximal coronary vasodilation (8). After a 10-min continuous infusion of adenosine, myocardial blood flow measurements (using different fluorescent-colored microspheres) were repeated without interruption of the adenosine administration.…”

“…For these animals, fetal weight was estimated with the equation W ϭ Woe (0.008 days). LV and RV free wall weights were estimated to be 2.24 and 1.99 g/kg estimated fetal weight, respectively (8).…”

“…Serum samples for determination of serum erythropoietin levels were obtained daily and stored at Ϫ80°C. Myocardial blood flow was determined in five fetuses using fluorescent microspheres as performed previously and described in detail below (8). The study concluded 24 h after the seventh phlebotomy (day 8 of study) (n ϭ 11).…”

Regulation of Myocardial Glucose Transporters GLUT1 and GLUT4 in Chronically Anemic Fetal Lambs

“…Myocardial blood flow was determined using fluorescent microspheres as described previously (18). Briefly, for each blood flow determination, approximately 1.2 ϫ 10 6 15 m fluorescentlabeled polystyrene microspheres (Triton Technology, San Diego, CA) suspended in 1 mL 0.9% NaCl with 0.02% Tween and 0.02% thimerosal, were injected into the left atrium and flushed with 2 mL 0.9% NaCl over a 30-s period.…”