Circulation. 2001;104:1012-1018
doi: 10.1161/hc3401.095073
doi: 10.1161/hc3401.095073
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(Circulation. 2001;104:1012.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Patients With End-Stage Congestive Heart Failure Treated With ß-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance
From the Cardiovascular Research Group, Department of Physiology and Section of Cardiology, Temple University School of Medicine, Philadelphia, Pa.
Correspondence to Steven R. Houser, PhD, Codirector, Cardiovascular Research Group, Department of Physiology, Temple University School of Medicine, 3400 N Broad St, Philadelphia, PA 19140. E-mail srhouser@ unix.temple.edu
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 (CHF). Clinical trials in CHF patients have shown that treatment with ß-adrenergic receptor antagonists (ßB) 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 ß B.
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 ßB-treated (ßB-CHF) and non–ßB treated (non-ßB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated cardiomyopathy (DCM, n=10), ICM with ßB therapy (ßB-ICM, n=12), and DCM with ßB therapy (ßB-DCM, n=12). Sarcoplasmic reticulum Ca2+ ATPase, phospholamban, and Na+-Ca2+ 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-ßB-CHF versus NF. Sarcoplasmic reticulum Ca2+ ATPase in the ßB-ICM and ßB-DCM was greater than in non-ßB-CHF and were not different than in NF. Ca2+ transients in non-ßB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca2+ transients from ßB-CHF myocytes had shorter durations than in ßB-CHF myocytes.
Conclusions— ßB treatment in CHF patients can normalize the abundance of myocyte Ca2+ regulatory proteins and improve Ca2+-handling.
Key Words: heart failure • sarcoplasmic reticulumCa2+-transporting ATPase • sodium-calcium exchanger • proteins, calcium regulatory
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