Left ventricular and aortic dysfunction in cystic fibrosis mice

Background: Left ventricular (LV) abnormalities have been reported in cystic fibrosis (CF); however, it remains unclear if loss of cystic fibrosis transmembrane conductance regulator (CFTR) function causes heart defects independent of lung disease. Methods: Using gut-corrected F508del CFTR mutant mice (δF508), which do not develop human lung disease, we examined in vivo heart and aortic function via 2D transthoracic echocardiography and LV catheterization. Results: δF508 mouse hearts showed LV concentric remodeling along with enhanced inotropy (increased +. dP/dt, fractional shortening, decreased isovolumetric contraction time) and greater lusitropy (- dP/dt, Tau). Aortas displayed increased stiffness and altered diastolic flow. β-adrenergic stimulation revealed diminished cardiac reserve (attenuated +. dP/dt,- dP/dt, LV pressure). Conclusions: In a mouse model of CF, CFTR mutation leads to LV remodeling with alteration of cardiac and aortic functions in the absence of lung disease. As CF patients live longer, more active lives, their risk for cardiovascular disease should be considered.