Little is known about human cardiac myocyte structure during normal development, or with congenital heart disease. We studied 46 ventricular myocytes from 20 normal hearts (patients age 7 weeks gestation to 19 years), and 12 myocytes from 5 patients with Tetralogy of Fallot. Tissue was obtained under the guidelines of approved institutional protocol #UUMC 5754-96. Pathologic specimens from normal hearts and surgical specimens from the right ventricular outflow tract of patients with Tetralogy of Fallot were fixed, post-fixed and sectioned using standard techniques, and the sections were imaged at 2,000X and 10,000X using a JEOL 100S or an Hitachi H7100. Cell surface to volume ratio, and the volume fractions of the intracellular organelles were calculated using standard stereologic techniques (line and point counting).

In myocytes from normal patients, cell dimensions and surface area increased while cell surface to volume ratio decreased with development. The myofibrils were initially sparse, poorly defined, and lined the cell periphery. Later in development, they formed rows and were found centrally. Longitudinal sarcoplasmic reticulum was present by the 2nd trimester, but T-tubules were not apparent until after birth. The volume fractions of the sarcoplasmic reticulum, myofibrils, and mitochondria increased during development.

In myocytes from patients with Tetralogy of Fallot, the volume fractions of the sarcoplasmic reticulum and myofibrils were larger than in normal, age-matched post-natal hearts (mean±SEM=3.5±0.4% vs. 1.6±0.2%, and 42.4±3.9% vs. 29.4±2.2% respectively), but the volume fraction of the mitochondria was the same.

In summary, an increase in the sarcoplasmic reticulum, myofibrils and mitochondria during development may account for the improved contractility in mature cardiac ventricular myocytes. The increased sarcoplasmic reticulum and myofibrils in Tetralogy of Fallot may represent either an abnormality associated with the disease, or the activation of compensatory mechanisms.