Effects of pre-natal and early post-natal undernutrition on adult internal thoracic artery function.
OBJECTIVE
Previous studies in humans and animals have suggested that undernutrition in utero and in early post-natal life may lead to altered vascular function in a number of peripheral arteries. We investigated the effect of pre- and post-natal nutrient restriction on the vascular reactivity of the left internal thoracic artery using a sheep model.


METHODS
Welsh mountain ewes were mated and assigned to three dietary groups: (1) 100% of total nutritional requirements (control, n=6); (2) 50% of total nutritional requirements during the first 31 days of gestation (n=6); and (3) 50% nutritional restriction during the first 31 days of gestation, followed by a restriction in the diet of their offspring 12-25 weeks post-natally, designed to produce a 15% reduction in growth trajectory (n=7). The male offspring were sacrificed at 130 weeks; the left internal thoracic artery was mounted onto a wire myograph and the reactivity of the vessel to various agonists measured.


RESULTS
The offspring of animals who underwent an early gestation nutrient restriction had a significantly increased basal tone (0.41+/-0.25 vs 6.34+/-1.35, p=0.015) and sensitivity to phenylephrine (log EC(50): -6.23+/-0.04 M vs -5.74+/-0.17 M, p=0.036) as compared with control animals. However, this phenomenon was not seen in animals that underwent both pre- and post-natal nutrient restriction.


CONCLUSIONS
Pre-natal undernutrition increases the basal tone and sensitivity of the left internal thoracic artery to phenylephrine. This effect is significantly attenuated by continued undernutrition in early post-natal life. These experiments suggest that in utero and early post-natal undernutrition may be important determinants of graft function in later life.
Khan
Omar A
OA
Department of Cardiothoracic Surgery, Southampton General Hospital, UK.
Torrens
Christopher
C
Noakes
David E
DE
Poston
Lucilla
L
Hanson
Mark A
MA
Green
Lucy R
LR
Ohri
Sunil K
SK
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D001699:Biometry; D004195:Disease Models, Animal; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology; D007387:Internal Mammary-Coronary Artery Anastomosis; D008297:Male; D044342:Malnutrition / Q000503:physiopathology*; D008323:Mammary Arteries / Q000196:embryology / Q000503:physiopathology* / Q000637:transplantation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D014661:Vasoconstriction; D014664:Vasodilation