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

Abstract

Background Alterations in Ca 2+ -handling proteins are thought to underlie the deranged Ca 2+ transients that contribute to deterioration of cardiac function in congestive heart failure (CHF). Clinical trials in CHF patients have shown that treatment with β-adrenergic receptor antagonists (βB) improves cardiac performance. The present study determined whether the abundance of Ca 2+ -handling proteins is different in failing hearts from patients treated or untreated with β B. Methods and Results Ca 2+ 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 βB-treated (βB-CHF) and non–βB treated (non-βB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated cardiomyopathy (DCM, n=10), ICM with βB therapy (βB-ICM, n=12), and DCM with βB therapy (βB-DCM, n=12). Sarcoplasmic reticulum Ca 2+ ATPase, phospholamban, and Na + -Ca 2+ exchanger protein abundance were determined by use of Western blot analysis. Ca 2+ transients were measured with fluo-3. Sarcoplasmic reticulum Ca 2+ ATPase was significantly less abundant whereas phospholamban and Na + -Ca 2+ exchanger were not significantly altered in non-βB-CHF versus NF. Sarcoplasmic reticulum Ca 2+ ATPase in the βB-ICM and βB-DCM was greater than in non-βB-CHF and were not different than in NF. Ca 2+ transients in non-βB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca 2+ transients from βB-CHF myocytes had shorter durations than in βB-CHF myocytes. Conclusions βB treatment in CHF patients can normalize the abundance of myocyte Ca 2+ regulatory proteins and improve Ca 2+ -handling.