A second protein, p38 MAP kinase, known to stimulate fibrosis and cell death, was twice as active in late-contracting parts of failing hearts in untreated dogs, than in the same heart zone of dogs who underwent pacemaker resynchronization therapy.
Other proteins that lead to heart cell death and worsen contraction were overexpressed in dogs with untreated heart failure, but not in the pacemaker-treated group. These included calcium-calmodulin-dependent kinase (CaMKII), which is linked to arrhythmia, and tumor necrosis factor-alpha (TNF), which is also tied to damaging inflammation and cell death.
The enzyme Akt, a promoter of cell survival when turned on, was markedly less active in the group whose hearts continued to beat out of sync.
Researchers next plan to look at how pacemakers stimulate biological changes in the heart, with the aim of developing treatments that bring the heart back to a normal, healthy state.
In cardiac resynchronization therapy, both major pumping chambers, known as the right and left ventricles, are stimulated at the same time with a biventricular pacemaker to optimize the muscles beat so that one side does not beat a short time before the other.
The American Heart Association estimates that more than 5 million Americans have some form of congestive heart failure, marked by symptoms such as shortness of breath and fatigue.
|Contact: David March|
Johns Hopkins Medical Institutions