Chronic partial unloading restores β-adrenergic responsiveness and reverses receptor downregulation in failing rat hearts

ObjectivesMechanical unloading with a left ventricular assist device promotes “reverse remodeling,” including restoration of β-adrenergic receptor signaling and function. We compared the effects of partial unloading and complete unloading on β-adrenergic responsiveness and gene expressions in failing rat hearts by use of heterotopic heart–lung or heart transplantation models.MethodsFour weeks after ligation of the left anterior descending artery in Lewis rats, rats with heart failure were divided into 3 groups: infarcted hearts and lungs transplanted into the recipient rats (heart failure–partial unloading, n = 8); infarcted hearts transplanted into the recipient rats (heart failure–complete unloading, n = 7); infarcted (heart failure, n = 8) hearts without transplantation. Normal rats (n = 7) were used as controls. Papillary muscle function and gene expressions were studied at 2 or 4 weeks after transplantation.ResultsIn 2-week models, baseline developed tension of papillary muscles significantly increased in heart failure–partial unloading and heart failure–complete unloading compared with heart failure (0.15 ± 0.07 and 0.12 ± 0.05 g/mm2 vs 0.02 ± 0.01 g/mm2, P < .05). However, in 4-week models, they decreased to 0.11 ± 0.03 and 0.10 ± 0.03 g/mm2. In 4-week but not in 2-week models, the increase from baseline in baseline developed tension produced by β-adrenergic stimulation (isoproterenol, 10−8 and 10−7 mol/L) was significantly increased in heart failure–partial unloading compared with heart failure–complete unloading and heart failure (P < .05). The mRNA expressions of brain natriuretic peptide and β1- and β2-adrenergic receptors were normalized in both 2- and 4-week models of heart failure–partial unloading.ConclusionsChronic partial unloading but not complete unloading improved β-adrenergic responsiveness and normalized brain natriuretic peptide and β1- and β2-adrenergic receptor mRNA expressions in the failing rat hearts