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Eur J Cardiothorac Surg 2005;28:811-815
© 2005 Elsevier Science NL

Effects of pre-natal and early post-natal undernutrition on adult internal thoracic artery function

^a Department of Cardiothoracic Surgery, Southampton General Hospital, UK
^b Centre for Developmental Origins of Health and Disease, University of Southampton, Princess Anne Hospital, Southampton SO16 5YA, UK
^c Department of Veterinary Reproduction, Royal Veterinary College, University of London, UK
^d Division of Reproductive Health, Endocrinology and Development, Guy's King's St Thomas Hospital, London, UK

Received 23 February 2005; received in revised form 18 August 2005; accepted 31 August 2005.

^_* Corresponding author. Tel.: +44 115 9691169; fax +44 115 8402605. (Email: m.hanson{at}soton.ac.uk).

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 EC₅₀: –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.

Key Words: Coronary artery bypass conduits • Vascular tone and reactivity

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