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

Background-Alterations in Ca2+-handling proteins are thought to underlie th e deranged Ca2+ transients that contribute to deterioration of cardiac func tion in congestive heart failure (CBF). Clinical trials in CHF patients hav e shown that treatment with beta -adrenergic receptor antagonists (betaB) i mproves cardiac performance. The present study determined whether the abund ance 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 my ocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF grou p) removed at transplantation. Analysis was performed in betaB-treated (bet aB-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 beta B therapy (betaB-DCM, n = 12 n = 12). Sarcoplasmic reticulum Ca2+ ATPase, p hospholamban, and Na+-Ca+ exchanger protein abundance were determined by us e of Western blot analysis. Ca2+ transients were measured with fluo-3. Sarc oplasmic reticulum Ca2+ ATPase was significantly less abundant whereas phos pholamban and Na+-Ca2+ exchanger were not significantly altered in non-beta B-CHF versus NF. Sarcoplasmic reticulum Ca2+ ATPase in the betaB-ICM and be taB-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 myoc ytes 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.