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Effects of pre-natal and early post-natal undernutrition on adult internal thoracic artery function
Omar A Khan1, Christopher Torrens, David E Noakes
1Department of Cardiothoracic Surgery, Southampton General Hospital, UK.
Insights
Prenatal nutrient restriction increased thoracic artery tone and phenylephrine sensitivity in sheep. Continued undernutrition postnatally attenuated these vascular changes, suggesting early nutrition impacts later graft function.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Nutritional Science
Background:
- Undernutrition during gestation and early life may alter peripheral artery vascular function.
- The impact of nutrient restriction on specific arteries, like the internal thoracic artery, requires further investigation.
Purpose of the Study:
- To investigate the effects of prenatal and postnatal nutrient restriction on the vascular reactivity of the left internal thoracic artery in a sheep model.
- To determine if early-life nutritional insults impact vascular function later in life.
Main Methods:
- Sheep were divided into control, prenatal nutrient restriction, and combined prenatal/postnatal nutrient restriction groups.
- Vascular reactivity of the left internal thoracic artery was measured using a wire myograph in male offspring at 130 weeks of age.
- Reactivity was assessed in response to various agonists, including phenylephrine.
Main Results:
- Early gestation nutrient restriction significantly increased basal tone and phenylephrine sensitivity in the left internal thoracic artery compared to controls.
- Combined prenatal and postnatal nutrient restriction did not result in increased basal tone or phenylephrine sensitivity.
- These findings indicate a potential protective or modifying effect of continued early postnatal undernutrition.
Conclusions:
- Prenatal undernutrition leads to increased basal tone and phenylephrine sensitivity in the left internal thoracic artery.
- Early postnatal undernutrition significantly attenuates the vascular effects of prenatal nutrient restriction.
- These results suggest that nutritional status in utero and early postnatally are critical determinants of vascular graft function later in life.
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.
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