Chronic pulmonary hypertension culminates in right heart failure and death in the majority of patients, and while survival rates for selected patients have been prolonged with the introduction of medical therapeutic agents, CPH remains invariably fatal. The long-range goals of this project are to determine the biomechanical and molecular changes that occur in the right atrium and ventricle during their progression from compensatory hypertrophy to dilated dysfunction consequent to prolonged exposure to elevated pulmonary pressures. Using two standard experimental models of chronic right ventricular pressure overload and chemically-induced pulmonary hypertension (monocrotaline pyrrole) in animals, chronic pulmonary hypertension and right heart failure will be created. Right heart mechanics will be studied using simultaneous bichamber conductance catheter technology, magnetic resonance imaging with finite element analysis for 3-dimensional right ventricular stress-strain mapping, and assessment of myocardial adrenergic receptors and calcium handling proteins. In addition, potential therapeutic options for molecular modulation (chronic 22-adrenergic stimulation) and hemodynamic unloading (interatrial shunting) will be studied. NARRATIVE: Right heart failure is the inevitable cause of death in patients with chronic pulmonary hypertension. This project seeks to determine the biomechanical and molecular changes that occur in the right atrium and ventricle during their progression from compensatory hypertrophy to dilated dysfunction. In addition, potential therapeutic options for molecular modulation (chronic 22-adrenergic stimulation) and hemodynamic unloading (interatrial shunting) will be studied.
