Patients With End-Stage Congestive Heart Failure Treated With b-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance

Background—Alterations in Ca-handling proteins are thought to underlie the deranged Ca transients that contribute to deterioration of cardiac function in congestive heart failure (CHF). Clinical trials in CHF patients have shown that treatment with b-adrenergic receptor antagonists (bB) improves cardiac performance. The present study determined whether the abundance of Ca-handling proteins is different in failing hearts from patients treated or untreated with bB. Methods and Results—Ca 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 bB-treated (bB-CHF) and non–bB treated (non-bB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n510), nonischemic dilated cardiomyopathy (DCM, n510), ICM with bB therapy (bB-ICM, n512), and DCM with bB therapy (bB-DCM, n512). Sarcoplasmic reticulum Ca ATPase, phospholamban, and Na-Ca exchanger protein abundance were determined by use of Western blot analysis. Ca transients were measured with fluo-3. Sarcoplasmic reticulum Ca ATPase was significantly less abundant whereas phospholamban and Na-Ca exchanger were not significantly altered in non-bB-CHF versus NF. Sarcoplasmic reticulum Ca ATPase in the bB-ICM and bB-DCM was greater than in non-bB-CHF and were not different than in NF. Ca transients in non-bB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca transients from bB-CHF myocytes had shorter durations than in bB-CHF myocytes. Conclusions—bB treatment in CHF patients can normalize the abundance of myocyte Ca regulatory proteins and improve Ca-handling. (Circulation. 2001;104:1012-1018.)