| Ca2+ clock malfunction in a canine model of pacing-induced heart failure. | |
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MedLine Citation:
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PMID: 20889842 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms of sinoatrial node (SAN) dysfunction in heart failure (HF) remain unclear. We hypothesized that impaired rhythmic spontaneous sarcoplasmic reticulum Ca(2+) release (Ca(2+) clock) plays an important role in SAN dysfunction in HF. HF was induced in canine hearts by rapid ventricular pacing. The location of pacemaking sites was determined in vivo using computerized electrical mapping in acute open-chest preparations (normal, n = 3; and HF, n = 4). Isoproterenol (Iso, 0.2 μg·kg(-1)·min(-1)) infusion increased heart rate and shifted the pacemaking site to the superior SAN in all normal hearts. However, in failing hearts, Iso did not induce superior shift of the pacemaking site despite heart rate acceleration. Simultaneous optical recording of intracellular Ca(2+) and membrane potential was performed in Langendorff-perfused isolated right atrium (RA) preparations from normal (n = 7) and failing hearts (n = 6). Iso increased sinus rate, enhanced late diastolic Ca(2+) elevation (LDCAE), and shifted the pacemaking sites to the superior SAN in all normal but in none of the HF RAs. Caffeine (2 ml, 20 mmol/l) caused LDCAE and increased heart rate in four normal RAs but in none of the three HF RAs. Iso induced ectopic beats from lower crista terminalis in five of six HF RAs. These ectopic beats were suppressed by ZD-7288, a specific pacemaker current (I(f)) blocker. We conclude that HF results in the suppression of Ca(2+) clock, resulting in the unresponsiveness of superior SAN to Iso and caffeine. HF also increases the ectopic pacemaking activity by activating the I(f) at the latent pacemaking sites in lower crista terminalis. |
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Authors:
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Tetsuji Shinohara; Hyung-Wook Park; Seongwook Han; Mark J Shen; Mitsunori Maruyama; Daehyeok Kim; Peng-Sheng Chen; Shien-Fong Lin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-01 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-03 Completed Date: 2011-01-13 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1805-11 Citation Subset: IM |
Affiliation:
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Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Agonists
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pharmacology Animals Caffeine / pharmacology Calcium Signaling* / drug effects Cardiac Pacing, Artificial* Circadian Clocks* / drug effects Disease Models, Animal Dogs Electrophysiologic Techniques, Cardiac Heart Failure / etiology, metabolism*, physiopathology Heart Rate* / drug effects Isoproterenol / pharmacology Membrane Potentials Perfusion Pyrimidines / pharmacology Sarcoplasmic Reticulum / metabolism Sinoatrial Node / drug effects, metabolism*, physiopathology Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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HL-71140/HL/NHLBI NIH HHS; P01-HL-78931/HL/NHLBI NIH HHS; R01-HL-78932/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Pyrimidines; 133059-99-1/ICI D2788; 58-08-2/Caffeine; 7683-59-2/Isoproterenol |
| Comments/Corrections | |
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