Logo image
Back
Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep
Journal article   Open access   Peer reviewed

Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep

Christopher E Mascio, Aaron K Olison, J Carter Ralphe, Robert J Tomanek, Thomas D Scholz and Jeffrey L Segar
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.289(6), pp.R1736-1745
12/2005
DOI: 10.1152/ajpregu.00278.2005
PMID: 16123231
url
https://doi.org/10.1152/ajpregu.00278.2005View
Published (Version of record) Open Access

Abstract

Little is known about the vascular and metabolic adaptations that take place in the fetal heart to maintain cardiac function in response to increased load. Chronic fetal anemia has previously been shown to result in increased ventricular mass, increased myocardial vascularization, and increased myocardial expression of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF). We therefore sought to determine whether chronic fetal anemia induces expression of HIF-1-regulated angiogenic factors and glycolytic enzymes in the fetal myocardium. Anemia was produced in chronically instrumented fetal sheep by daily isovolemic hemorrhage (80-100 ml) for either 3 (n = 4) or 7 days (n = 11) beginning at 134 days of gestation (term 145 days). Catheterized, nonbled twins served as controls. Isovolemic hemorrhage over 7 days resulted in decreased fetal hematocrit (37 +/- 1 to 20 +/- 1%) and arterial oxygen content (6.5 +/- 0.4 to 2.8 +/- 0.2 ml O2/dl). Myocardial blood flow and vascularization were significantly increased after 7 days of anemia. Myocardial HIF-1 protein expression and VEGF (left ventricular), VEGF receptor-1 (right ventricular), and VEGF receptor-2 (right ventricular, left ventricular) mRNA levels were elevated (P < 0.05) in 7-day anemic compared with control animals. Myocardial expressions of the glycolytic enzymes aldolase, lactate dehydrogenase A, phosphofructokinase (liver), and phosphoglycerol kinase were also significantly elevated after 7 days of anemia. Despite the absence of a significant increase in myocardial HIF-1alpha protein in 3-day anemic fetuses, expressions of VEGF, VEGF receptor-1, and the glycolytic enzymes were greater in 3-day compared with 7-day anemic animals. These data suggest that HIF-1 likely participates in the fetal myocardial response to anemia by coordinating an increase in gene expressions that promote capillary growth and anaerobic metabolism. However, factors other than HIF-1 also appear important in the regulation of these genes. We speculate that the return of mRNA levels of angiogenic and glycolytic enzymes toward control levels in the 7-day anemic fetus is explained by a significantly increased resting myocardial blood flow, resulting from coronary vascular growth and increased coronary conductance, and a return to a state of adequate oxygen and nutrient delivery, obviating the need for enhanced transcription of genes encoding angiogenic and glycolytic enzymes.
 Adaptation, Physiological Anemia - physiopathology Coronary Circulation Fetal Diseases - physiopathology Anemia - embryology Animals Gene Expression Regulation, Developmental Neovascularization, Pathologic - physiopathology Sheep Neovascularization, Pathologic - embryology Chronic Disease Hypoxia-Inducible Factor 1 - metabolism

Details

Metrics

15 Record Views
22 Times Cited - Web of Science
Logo image