Adapting to a new environment: postnatal maturation of the human cardiomyocyte

Abstract

The postnatal mammalian heart undergoes remarkable developmental changes, which are stimulated by the transition from the intrauterine to extrauterine environment. With birth, increased oxygen levels promote metabolic, structural and biophysical maturation of cardiomyocytes, resulting in mature muscle with increased efficiency, contractility and electrical conduction. In this Topical Review article, we highlight key studies that inform our current understanding of human cardiomyocyte maturation. Collectively, these studies suggest that human atrial and ventricular myocytes evolve quickly within the first year but might not reach a fully mature adult phenotype until nearly the first decade of life. However, it is important to note that fetal, neonatal and paediatric cardiac physiology studies are hindered by a number of limitations, including the scarcity of human tissue, small sample size and a heavy reliance on diseased tissue samples, often without age-matched healthy controls. Future developmental studies are warranted to expand our understanding of normal cardiac physiology/pathophysiology and inform age-appropriate treatment strategies for cardiac disease.

Keywords: age dependence; cardiac electrophysiology; cardiomyocyte; development; excitation-contraction coupling; human physiology; maturation.

Figure 1.. Electron microscopy of fetal hearts

A, fetal hearts at 20 weeks of gestation, with some desmosomes forming at intercalated disc (arrows). Note scattered myofibrils. B, fetal heart at 30 weeks of gestation, with more abundant desmosomes at the intercalated disc and more densely packed myofibrils. Arrows indicate sarcoplasmic reticulum tubules at the Z-line, which were not present in the earlier period. Abbreviations: d, desmosomes; fa, fascia adherens; gj, gap junctions; mf, myofibrils. Scale bars: 0.53 μM. Adapted with permission from Kim et al. (1992).

Figure 2.. Action potential morphology differs between neonatal and adult human atrial cardiomyocytes

Action potential waveforms recorded at stimulation cycle lengths (CL) of 1000 and 400 ms. Adapted with permission from Wang et al. (2003).