Studies examine issues in pediatric cardiology

"Overall experience proves that PPVI is not only feasible, but provides an important benefit to patients who would otherwise have to endure additional surgeries. In addition, our data clearly demonstrates that changes in technique resulted in a significant improvement in the need for device removal, and further progress is expected in the future,” said Dr. Khambadkone.

Philipp Lurz will present this study on Monday, March 26, at 4:15 p.m. in room 228.

Developmental Changes in the Modulation of Contractility in Human Ventricle (Presentation Number: 1011-33)

The ability of the heart’s ventricles to contract, known as contractility, has been shown to increase with age in animal models. Treatments to alter contractility, particularly after surgery, have been well established in adult patients. However, because few studies have measured contractility in the ventricles of infants, it is unknown whether treatments designed for adults following heart surgery are beneficial or harmful to this patient population.

A study conducted at Emory University and Children’s Healthcare of Atlanta in Georgia examined developmental changes in the effects of drugs and the response to stimulation rate in human right ventricle tissue during the first year of life. Specifically, researchers compared tissue from newborns (less than one week, n=5) undergoing shunt implantation for left side underdevelopment, to tissue from infants (three to 12 months, n=6) undergoing repair for Tetralogy of Fallot, a congenital heart disease involving four structural defects in the heart. Tissue removed from the right ventricle as part of the surgical repair was obtained directly from the operating room and immediately studied in the lab.

Researchers electrically stimulated the tissue to produce contractions and measure the tension produced by the tissue. They then applied 100 nM isoproterenol or 10 µM forskolin (drugs used to stimulate the heart via cell signaling) in order to determine the effect of these drugs on the contractility of the tissue. They also measured the force frequency relationship, or FFR, which is the response of the tissue to faster stimulation rates. Additionally, the study determined the levels of three proteins involved in contractility and calcium balance in the heart, including Na/Ca Exchanger (NCX), SR Ca-ATPase (SERCA) and phospholamban (PLB). Results showed that:

• Response to isoproterenol and forskolin were significantly smaller in newborn ventricle tissue compared to infant (152 vs. 292 % of control for isoproterenol and 183 vs. 380 % of control for forskolin).
  
  
• Typically, when the adult heart beats faster it also beats with more force and is able to pump more blood to the body, and thus is said to have a posititve FFR. In this study, researchers found that FFR for newborns was flat, with no increase in developed force at faster rates of stimulation, whereas infant tissues had a significantly positive FFR, increasing to 182 percent of control at the fastest rate of stimulation.
  
  
• NCX levels were two fold higher in newborns than in infants, whereas the levels of PLB were significantly smaller in the newborn group. The levels of SERCA were unchanged between newborns or infants. The differences in the levels of these proteins may underlie the poor regulation of contractility seen in the newborn tissue.