Intrauterine growth restriction (IUGR) is associated with impaired cardiac function in childhood and is linked to short- and long-term morbidities. Placental dysfunction underlies most IUGR, and causes fetal oxidative stress which may impact on cardiac development. Accordingly, we investigated whether antenatal
melatonin treatment, which possesses
antioxidant properties, may afford cardiovascular protection in these vulnerable fetuses. IUGR was induced in sheep fetuses using
single umbilical artery ligation on day 105-110 of pregnancy (term 147). Study 1:
melatonin (2 mg h(-1)) was administered i.v. to ewes on days 5 and 6 after surgery. On day 7 fetal heart function was assessed using a Langendorff apparatus. Study 2: a lower dose of
melatonin (0.25 mg h(-1)) was administered continuously following IUGR induction and the ewes gave birth normally at term. Lambs were killed when 24 h old and coronary vessels studied.
Melatonin significantly improved fetal oxygenation in vivo. Contractile function in the right ventricle and coronary flow were enhanced by
melatonin. Ischaemia-reperfusion-induced
infarct area was 3-fold greater in IUGR hearts than in controls and this increase was prevented by
melatonin. In isolated neonatal coronary arteries, endothelium-dependent
nitric oxide (NO) bioavailability was reduced in IUGR, and was rescued by modest
melatonin treatment.
Melatonin exposure also induced the emergence of an
indomethacin-sensitive vasodilation. IUGR caused marked stiffening of the coronary artery and this was prevented by
melatonin. Maternal
melatonin treatment reduces fetal hypoxaemia, improves heart function and coronary blood flow and rescues cardio-coronary deficit induced by IUGR.