Patients with end-stage congestive heart failure treated with β-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance

Background-Alterations in Ca2+-handling proteins are thought to underlie the deranged Ca2+ transients that contribute to deterioration of cardiac function in congestive heart failure (CBF). Clinical trials in CHF patients have shown that treatment with beta -adrenergic receptor antagonists (betaB) improves cardiac performance. The present study determined whether the abundance of Ca2+-handling proteins is different in failing hearts from patients treated or untreated with betaB. Methods and Results-Ca2+ regulatory protein abundance was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF group) removed at transplantation. Analysis was performed in betaB-treated (betaB-CHF) and non-betaB treated (non-betaB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n = 10), nonischemic dilated cardiomyopathy (DCM, n = 10), ICM with betaB therapy (betaB-ICM, n = 12), and DCM with betaB therapy (betaB-DCM, n = 12 n = 12). Sarcoplasmic reticulum Ca2+ ATPase, phospholamban, and Na+-Ca+ exchanger protein abundance were determined by use of Western blot analysis. Ca2+ transients were measured with fluo-3. Sarcoplasmic reticulum Ca2+ ATPase was significantly less abundant whereas phospholamban and Na+-Ca2+ exchanger were not significantly altered in non-betaB-CHF versus NF. Sarcoplasmic reticulum Ca2+ ATPase in the betaB-ICM and betaB-DCM was greater than in non-betaB-CHF and were not different than in NF. Ca2+ transients in non-betaB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca2+ transients from betaB-CHF myocytes had shorter durations than in betaB-CHF myocytes. Conchtsions-betaB treatment in CHF patients can normalize the abundance of myocyte Ca2+ regulatory proteins and improve Ca2+-handling.