Glucocorticoid treatment does not alter early cardiac adaptations to growth restriction in preterm sheep fetuses.
OBJECTIVE
To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function.


METHODS
Laboratory.


METHODS
Sheep.


METHODS
Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles.


METHODS
Ventricular contractile function and infarct area following ischaemia/reperfusion.


RESULTS
The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to β-adrenoceptor activation were increased.


CONCLUSIONS
Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle β-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.
Department of Physiology, Monash University, Clayton, Vic, Australia.
M
M
Tare
S L
SL
Miller
E M
EM
Wallace
A E
AE
Sutherland
T
T
Yawno
H A
HA
Coleman
G
G
Jenkin
H C
HC
Parkington
D000222:Adaptation, Physiological / Q000187:drug effects* / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005318:Fetal Heart / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006340:Heart Rate, Fetal / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008026:Ligation; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000196:embryology; D034561:Sheep, Domestic; D014469:Umbilical Arteries; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D001623:Betamethasone; D007545:Isoproterenol