PMID- 16123231
OWN - NLM
STAT- MEDLINE
DCOM- 20060110
LR  - 20200930
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 289
IP  - 6
DP  - 2005 Dec
TI  - Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep.
PG  - R1736-45
AB  - 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.
FAU - Mascio, Christopher E
AU  - Mascio CE
AD  - Dept. of Surgery, Univ. of Iowa Carver College of Medicine, Iowa City, IA 52242, 
      USA.
FAU - Olison, Aaron K
AU  - Olison AK
FAU - Ralphe, J Carter
AU  - Ralphe JC
FAU - Tomanek, Robert J
AU  - Tomanek RJ
FAU - Scholz, Thomas D
AU  - Scholz TD
FAU - Segar, Jeffrey L
AU  - Segar JL
LA  - eng
GR  - T32-HL-07413/HL/NHLBI NIH HHS/United States
GR  - R01-HL-64770/HL/NHLBI NIH HHS/United States
GR  - T32 HL007413/HL/NHLBI NIH HHS/United States
GR  - K02-HL-04495/HL/NHLBI NIH HHS/United States
GR  - R01-HL-075446/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20050825
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Hypoxia-Inducible Factor 1)
SB  - IM
MH  - Adaptation, Physiological
MH  - Anemia/*embryology/*physiopathology
MH  - Animals
MH  - Chronic Disease
MH  - *Coronary Circulation
MH  - Fetal Diseases/*physiopathology
MH  - Gene Expression Regulation, Developmental
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Neovascularization, Pathologic/*embryology/*physiopathology
MH  - Sheep
EDAT- 2005/08/27 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/08/27 09:00
PHST- 2005/08/27 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/08/27 09:00 [entrez]
AID - 00278.2005 [pii]
AID - 10.1152/ajpregu.00278.2005 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1736-45. doi: 
      10.1152/ajpregu.00278.2005. Epub 2005 Aug 25.