Table 4.

Developmental changes in cardiomyocyte metabolism

Age range	Cardiomyocyte type	Key points	Citation
<0 years	Right and left ventricle	Mitochondrial mass increases throughout life Sparse, circular mitochondria in early fetal period; with variable shapes, increased size, increased mitochondrial density, aggregation near nuclei and myofibrils later in fetal development.	Kim et al. (1992)
<0–90 years	Left ventricle	Mitochondrial mass and DNA content are increased in adult cardiomyocytes	Pohjoismaki et al. (2013)
5–45 years	Left ventricle	Correlation between mitochondrial density, heart rate and oxygen consumption Mitochondrial density increases, occupying ~25% of adult cardiomyocyte volume	Schaper et al. (1985); Barth et al. (1992)
<0 years	Whole heart	Metabolic genes upregulated throughout gestation Genes involved in fatty acid metabolism (FABP4, FABP2 and RBP) are upregulated between first and second trimester	Iruretagoyena et al. ((2014a)
<0–22 years	Ventricles	Increased mitochondrial activity during perinatal period Mitochondrial DNA content and mitochondrial enzymes (citrate synthase, complex IV, ATP synthase, cytochrome c oxidase) increase with gestational and postnatal age	Marin-Garcia et al. (1989); Marin-Garcia et al. (2000)
<1 year	Right ventricle	Age-dependent maturation of fatty acid oxidation Increase in proteins associated with fatty acid oxidation (malonyl coA decarboxylase); decrease in inhibitory regulators of fatty acid oxidation (acetyl CoA carboxylase, 5’-AMP-activated protein kinase)	Yatscoff et al. (2008)
<2 years	Left atria	Cyanotic congenital heart disease disturbs metabolic maturation Cyanotic heart samples have reduced protein synthesis and downregulation of aerobic energy metabolism, in comparison to acyanotic heart samples	Dong et al. (2021)
0–9 years	Right ventricle	Age and disease impact metabolic maturation Younger patients had lower ATP/ADP ratio. Cyanotic heart samples had higher lactate levels	Modi et al. (2004)