Postnatal undernutrition in mice causes cardiac arrhythmogenesis which is exacerbated when pharmacologically stressed

J Dev Orig Health Dis. 2018 Aug;9(4):417-424. doi: 10.1017/S2040174418000156. Epub 2018 Apr 12.


Growth restriction caused by postnatal undernutrition increases risk for cardiovascular disease in adulthood with the potential to induce arrhythmogenesis. Thus, the purpose was to determine if undernutrition during development produced arrhythmias at rest and when stressed with dobutamine in adulthood. Mouse dams were fed (CON: 20% protein), or low-protein (LP: 8%) diet before mating. A cross-fostering model was used where pups nursed by dams fed LP diet in early [EUN; postnatal day (PN) 1-10], late (LUN; PN11-21) and whole (PUN; 1-21) phases of postnatal life. Weaned pups were switched to CON diets for the remainder of the study (PN80). At PN80, body composition (magnetic resonance imaging), and quantitative electrocardiogram (ECG) measurements were obtained under 1% isoflurane anesthesia. After baseline ECG, an IP injection (1.5 µg/g body weight) of dobutamine was administered and ECG repeated. Undernutrition significantly (P<0.05) reduced body weight in LUN (22.68±0.88 g) and PUN (19.96±0.32 g) but not in CON (25.05±0.96 g) and EUN (25.28±0.9207 g). Fat mass decreased in all groups compared with controls (CON: 8.00±1.2 g, EUN: 6.32±0.65 g, LUN: 5.11±1.1 g, PUN: 3.90±0.25 g). Lean mass was only significantly reduced in PUN (CON: 17.99±0.26 g, EUN: 17.78±0.39 g, LUN: 17.34±0.33 g, PUN: 15.85±0.28 g). Absolute heart weights were significantly less from CON, with PUN having the smallest. ECG showed LUN had occurrences of atrial fibrillation; EUN had increases of 1st degree atrioventricular block upon stimulation, and PUN had increased risk for ventricular depolarization arrhythmias. CON did not display arrhythmias. Undernutrition in early life resulted in ventricular arrhythmias under stressed conditions, but undernutrition occurring in later postnatal life there is an increased incidence of atrial arrhythmias.

Keywords: Developmental Origins of Health and Disease; cardiovascular arrhythmias; developmental programming.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arrhythmias, Cardiac / etiology*
  • Arrhythmias, Cardiac / pathology*
  • Cardiotonic Agents / toxicity
  • Diet, Protein-Restricted / adverse effects*
  • Dobutamine / toxicity*
  • Female
  • Male
  • Malnutrition / complications*
  • Mice
  • Stress, Physiological*


  • Cardiotonic Agents
  • Dobutamine