Prenatal diet determines susceptibility to cardiac ischaemia-reperfusion injury following treatment with diethylmaleic acid and N-acetylcysteine

Elmes, Matthew J.; McMullen, Sarah; Gardner, David S.; Langley-Evans, Simon C.

Abstract

Fetal undernutrition programmes increased risk of developing cardiovascular disease in adult life. We hypothesized that prenatal protein restriction would impair recovery in post-ischaemic cardiac function in adult offspring through antioxidant-mediated processes. Pregnant Wistar rats were fed control or maternal low protein diets (MLP) throughout gestation. The offspring of these rats were treated with either saline, N-acetylcysteine (NAC), diethylmaleate (DEM), or both NAC and DEM to manipulate glutathione status at 6 months of age. Hearts were rapidly excised and retro-perfused (Langendorff) to assess isolated cardiac function before (baseline), and during 30 min global ischaemia and 60 min reperfusion. Hearts from adult rats exposed to a MLP diet in utero suffered greater cardiac dysfunction than those from controls following 30 min ischaemia. Left ventricular developed pressure (LVDP) was significantly reduced upon early reperfusion (p < 0.042) in MLP rats compared to controls. NAC pre-treatment had no effect on LVDP of hearts from control animal hearts but improved the revival of MLP hearts to the same level as controls. DEM treatment did not affect control hearts but significantly reduced recovery of LVDP of MLP hearts during early (p < 0.008) and late reperfusion (0.035). Combined NAC and DEM treatment had no effect on LVDP between control and MLP fed offspring. Prenatal protein restriction throughout pregnancy increases the susceptibility of the adult rat heart to suffer a functional deficit following ischaemia-reperfusion injury. Pharmacologically improving antioxidant status prevented this injury. A nutritionally-imbalanced developmental environment may increase susceptibility to coronary heart disease through the programming of myocardial glutathione metabolism. © 2007 Elsevier Inc. All rights reserved.

Citation

Elmes, M. J., McMullen, S., Gardner, D. S., & Langley-Evans, S. C. (2008). Prenatal diet determines susceptibility to cardiac ischaemia-reperfusion injury following treatment with diethylmaleic acid and N-acetylcysteine. Life Sciences, 82(3-4), 149-155. https://doi.org/10.1016/j.lfs.2007.10.022

• Journal Article Type: Article
• Acceptance Date: Oct 25, 2007
• Online Publication Date: Nov 13, 2007
• Publication Date: Jan 16, 2008
• Deposit Date: Mar 4, 2025
• Journal: Life Sciences
• Print ISSN: 0024-3205
• Electronic ISSN: 1879-0631
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 82
• Issue: 3-4
• Pages: 149-155
• DOI: https://doi.org/10.1016/j.lfs.2007.10.022
• Public URL: https://nottingham-repository.worktribe.com/output/3085009
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S0024320507008053?via%3Dihub