Annually, 15 million babies globally will undergo growth deficits from an inadequate postnatal nutritive environment. Growth restriction during key developmental windows can lead to the occurrence of chronic disease in adulthood such cardiovascular disease [CVD]. The purpose of this dissertation was to characterize heart function following postnatal growth restriction. Investigations were performed to reveal alterations in electrical conductance, cardiac protein abundance, and cardiac energetics from postnatal growth restriction.To experimentally represent postnatal growth restriction, FVB mice were used since they do not discard their neonates when managed, thus allowing for cross fostering. Two weeks prior to mating, dams were nourished with either a control [CON; 20% protein diet], or a low protein diet [LP; 8% protein diet]. Mouse pups that are nourished from LP dams experience growth restriction from an 18% reduction of milk volume. After birth [postnatal day 1; PN1], pups from LP dams were euthanized while half of the pups from CON dams were cross fostered to a either a LP dam or a different CON dam. At PN21, all pups were weaned and fed CON diet ad libitum until adulthood at PN80. Therefore, our nutritive model isolated growth restriction to the postnatal developmental window in early life.At PN80, CON, EUN, LUN and PUN mice were placed under anesthesia and a 5-minute ECG was recorded at baseline. Next, the heart was pharmacologically stressed with an intraperitoneal [IP] injection of dobutamine, and another 5 minutes of ECG was recorded for all groups. ECG showed the CON mice did not experience any abnormal arrhythmias. However, in the restricted groups, the LUN had a higher prevalence of atrial flutter, EUN had 1st degree AV block, and PUN had an increased risk for ventricular depolarization arrhythmias. These results led to the conclusion that postnatal growth restriction increased the risk of abnormal electrical activity of the heart during adulthood, with the most severe impairments present in the PUN.The goal for the second study was to determine proteomic alterations between the hearts of CON and PUN mice. Thus, at PN21, hearts of CON and PUN were subjected to two-dimensional in-gel electrophoresis [2D DIGE] and mass spectroscopy to identify differences in cardiac protein abundance. Cardiac function was measured in adulthood via echocardiography. Results showed a reduced protein abundance of p57kip2, Ttn, and collagen proteins. Additionally, PUN mice had diastolic dysfunction in adulthood. Next, we constructed a potential mechanism for cardiac impairment to allow for future therapeutic countermeasures.The last project determined if growth restriction impaired mitochondrial energetics in the hearts of the PUN mice. Oxygen flux [JO2], and reactive oxygen species [ROS] were recorded using O2k-High resolution respirometry [HRR] at PN22 and PN80. Results from this investigation showed that postnatal growth restriction caused elevations in LEAK respirometry, which reduced the efficiency of PUN mitochondria. ROS emission was also significantly elevated in the PUN mouse hearts, indicating oxidative stress. In conclusion, postnatal growth restriction in early life impairs cardiac mitochondrial function and may increase the risk for CVD.Results from this dissertation show postnatal growth restriction causes permanent damage to cardiac structure and function in adulthood. Future research should focus on determining evidence-based practices with therapeutic countermeasures to mitigate the damage and counteract CVD in those that have experienced postnatal growth restriction.
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