Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling
Background Alternans in action potential voltage (APV-ALT) at heart rates 400% for CL 500% at CL
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| Veröffentlicht in: | Heart rhythm 2010-08, Vol.7 (8), p.1093-1101 |
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| container_title | Heart rhythm |
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| creator | Bayer, Jason D., MS Narayan, Sanjiv M., MD, FHRS Lalani, Gautam G., MD Trayanova, Natalia A., PhD, FHRS, FAHA |
| description | Background Alternans in action potential voltage (APV-ALT) at heart rates 400% for CL 500% at CL |
| doi_str_mv | 10.1016/j.hrthm.2010.04.008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_749017343</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S1547527110003449</els_id><sourcerecordid>749017343</sourcerecordid><originalsourceid>FETCH-LOGICAL-c524t-9461ad246c8aff2a73ac884340977b533d5def87eeee21d1aaa319dec0764e2f3</originalsourceid><addsrcrecordid>eNqFkUuPFCEUhStG44yjv8DEsHNV7eVRRdVCEzPxlUxi4mNNbsMtm5aiWqBM5t9L2aMLN7KACznnAN9tmqccdhx4_-K4O6RymHcC6gmoHcBwr7nkXde3ctD8_lYr3XZC84vmUc5HADH2IB82FwLkIETfXzb5ExZqHZ0oOoqFoS1-iey0lLrzGBiGQilizMxHdlhnrDNhKmxCH9ZEzM-n4G1NyQz3cUlzNflYEloKYQ2YmMVg_TqzA0YXfPz2uHkwYcj05G69ar6-ffPl-n178_Hdh-vXN63thCrtqHqOTqjeDjhNArVEOwxKKhi13ndSus7RNGiqQ3DHEVHy0ZEF3SsSk7xqnp9zT2n5sVIuZvZ5exVGWtZstBqBa6lkVcqz0qYl50STOSU_Y7o1HMwG2xzNb9hmg21AmQq7up7d5a_7mdxfzx-6VfDyLKD6y5-eksnWU7TkfCJbjFv8fy549Y_fVn4VdvhOt5SPy1o7E7LhJgsD5vPW763dHACkUqP8BcFMqTk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>749017343</pqid></control><display><type>article</type><title>Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Bayer, Jason D., MS ; Narayan, Sanjiv M., MD, FHRS ; Lalani, Gautam G., MD ; Trayanova, Natalia A., PhD, FHRS, FAHA</creator><creatorcontrib>Bayer, Jason D., MS ; Narayan, Sanjiv M., MD, FHRS ; Lalani, Gautam G., MD ; Trayanova, Natalia A., PhD, FHRS, FAHA</creatorcontrib><description>Background Alternans in action potential voltage (APV-ALT) at heart rates <110 bpm is a novel index to predict ventricular arrhythmias. However, the rate dependency of APV-ALT and its mechanisms in failing versus nonfailing human myocardium are poorly understood. It is hypothesized that APV-ALT in human heart failure (HF) reflects abnormal calcium handling. Objective Using a modeling and clinical approach, our objectives were to (1) determine how APV-ALT varies with pacing rate and (2) ascertain whether abnormalities in calcium handling explain the rate dependence of APV-ALT in HF. Methods APV-ALT was analyzed at several cycle lengths (CLs) using a dynamic pacing protocol applied to a human left ventricle wedge model with various alterations in calcium handling. Modeled APV-ALT was used to predict APV-ALT in left ventricle monophasic action potentials recorded from HF (n = 3) and control (n = 2) patients with the same pacing protocol. Results Reducing the sarcoplasmic reticulum calcium uptake current ≤25%, the release current ≤11%, or the sarcolemmal L-type calcium channel current ≤43% of control predicted APV-ALT to arise at CL ≥600 ms and then increase in magnitude by >400% for CL <400 ms. In HF patients, APV-ALT arose at CL = 600 ms and then increased in magnitude by >500% at CL <350 ms. For all other model alterations and for control patients, APV-ALT occurred only at CL <500 ms. Conclusions APV-ALT shows differing rate dependence in HF versus control patients, arising at slower rates in HF and predicted by models with abnormal calcium handling. Future studies should investigate whether APV-ALT at slow rates identifies patients with deranged calcium handing, including HF patients before decompensation or at risk for arrhythmias.</description><identifier>ISSN: 1547-5271</identifier><identifier>EISSN: 1556-3871</identifier><identifier>DOI: 10.1016/j.hrthm.2010.04.008</identifier><identifier>PMID: 20382266</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Action potential alternans ; Action Potentials - physiology ; Aged ; Arrhythmias, Cardiac - etiology ; Arrhythmias, Cardiac - physiopathology ; Calcium - metabolism ; Calcium handling ; Calcium Metabolism Disorders - complications ; Calcium Metabolism Disorders - physiopathology ; Cardiac Pacing, Artificial ; Cardiovascular ; Computer modeling ; Heart failure ; Heart Failure - complications ; Heart Failure - physiopathology ; Heart Rate - physiology ; Humans ; Middle Aged ; Models, Cardiovascular</subject><ispartof>Heart rhythm, 2010-08, Vol.7 (8), p.1093-1101</ispartof><rights>Heart Rhythm Society</rights><rights>2010 Heart Rhythm Society</rights><rights>Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-9461ad246c8aff2a73ac884340977b533d5def87eeee21d1aaa319dec0764e2f3</citedby><cites>FETCH-LOGICAL-c524t-9461ad246c8aff2a73ac884340977b533d5def87eeee21d1aaa319dec0764e2f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.hrthm.2010.04.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20382266$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bayer, Jason D., MS</creatorcontrib><creatorcontrib>Narayan, Sanjiv M., MD, FHRS</creatorcontrib><creatorcontrib>Lalani, Gautam G., MD</creatorcontrib><creatorcontrib>Trayanova, Natalia A., PhD, FHRS, FAHA</creatorcontrib><title>Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling</title><title>Heart rhythm</title><addtitle>Heart Rhythm</addtitle><description>Background Alternans in action potential voltage (APV-ALT) at heart rates <110 bpm is a novel index to predict ventricular arrhythmias. However, the rate dependency of APV-ALT and its mechanisms in failing versus nonfailing human myocardium are poorly understood. It is hypothesized that APV-ALT in human heart failure (HF) reflects abnormal calcium handling. Objective Using a modeling and clinical approach, our objectives were to (1) determine how APV-ALT varies with pacing rate and (2) ascertain whether abnormalities in calcium handling explain the rate dependence of APV-ALT in HF. Methods APV-ALT was analyzed at several cycle lengths (CLs) using a dynamic pacing protocol applied to a human left ventricle wedge model with various alterations in calcium handling. Modeled APV-ALT was used to predict APV-ALT in left ventricle monophasic action potentials recorded from HF (n = 3) and control (n = 2) patients with the same pacing protocol. Results Reducing the sarcoplasmic reticulum calcium uptake current ≤25%, the release current ≤11%, or the sarcolemmal L-type calcium channel current ≤43% of control predicted APV-ALT to arise at CL ≥600 ms and then increase in magnitude by >400% for CL <400 ms. In HF patients, APV-ALT arose at CL = 600 ms and then increased in magnitude by >500% at CL <350 ms. For all other model alterations and for control patients, APV-ALT occurred only at CL <500 ms. Conclusions APV-ALT shows differing rate dependence in HF versus control patients, arising at slower rates in HF and predicted by models with abnormal calcium handling. Future studies should investigate whether APV-ALT at slow rates identifies patients with deranged calcium handing, including HF patients before decompensation or at risk for arrhythmias.</description><subject>Action potential alternans</subject><subject>Action Potentials - physiology</subject><subject>Aged</subject><subject>Arrhythmias, Cardiac - etiology</subject><subject>Arrhythmias, Cardiac - physiopathology</subject><subject>Calcium - metabolism</subject><subject>Calcium handling</subject><subject>Calcium Metabolism Disorders - complications</subject><subject>Calcium Metabolism Disorders - physiopathology</subject><subject>Cardiac Pacing, Artificial</subject><subject>Cardiovascular</subject><subject>Computer modeling</subject><subject>Heart failure</subject><subject>Heart Failure - complications</subject><subject>Heart Failure - physiopathology</subject><subject>Heart Rate - physiology</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Models, Cardiovascular</subject><issn>1547-5271</issn><issn>1556-3871</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuPFCEUhStG44yjv8DEsHNV7eVRRdVCEzPxlUxi4mNNbsMtm5aiWqBM5t9L2aMLN7KACznnAN9tmqccdhx4_-K4O6RymHcC6gmoHcBwr7nkXde3ctD8_lYr3XZC84vmUc5HADH2IB82FwLkIETfXzb5ExZqHZ0oOoqFoS1-iey0lLrzGBiGQilizMxHdlhnrDNhKmxCH9ZEzM-n4G1NyQz3cUlzNflYEloKYQ2YmMVg_TqzA0YXfPz2uHkwYcj05G69ar6-ffPl-n178_Hdh-vXN63thCrtqHqOTqjeDjhNArVEOwxKKhi13ndSus7RNGiqQ3DHEVHy0ZEF3SsSk7xqnp9zT2n5sVIuZvZ5exVGWtZstBqBa6lkVcqz0qYl50STOSU_Y7o1HMwG2xzNb9hmg21AmQq7up7d5a_7mdxfzx-6VfDyLKD6y5-eksnWU7TkfCJbjFv8fy549Y_fVn4VdvhOt5SPy1o7E7LhJgsD5vPW763dHACkUqP8BcFMqTk</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Bayer, Jason D., MS</creator><creator>Narayan, Sanjiv M., MD, FHRS</creator><creator>Lalani, Gautam G., MD</creator><creator>Trayanova, Natalia A., PhD, FHRS, FAHA</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100801</creationdate><title>Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling</title><author>Bayer, Jason D., MS ; Narayan, Sanjiv M., MD, FHRS ; Lalani, Gautam G., MD ; Trayanova, Natalia A., PhD, FHRS, FAHA</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c524t-9461ad246c8aff2a73ac884340977b533d5def87eeee21d1aaa319dec0764e2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Action potential alternans</topic><topic>Action Potentials - physiology</topic><topic>Aged</topic><topic>Arrhythmias, Cardiac - etiology</topic><topic>Arrhythmias, Cardiac - physiopathology</topic><topic>Calcium - metabolism</topic><topic>Calcium handling</topic><topic>Calcium Metabolism Disorders - complications</topic><topic>Calcium Metabolism Disorders - physiopathology</topic><topic>Cardiac Pacing, Artificial</topic><topic>Cardiovascular</topic><topic>Computer modeling</topic><topic>Heart failure</topic><topic>Heart Failure - complications</topic><topic>Heart Failure - physiopathology</topic><topic>Heart Rate - physiology</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Models, Cardiovascular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bayer, Jason D., MS</creatorcontrib><creatorcontrib>Narayan, Sanjiv M., MD, FHRS</creatorcontrib><creatorcontrib>Lalani, Gautam G., MD</creatorcontrib><creatorcontrib>Trayanova, Natalia A., PhD, FHRS, FAHA</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Heart rhythm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bayer, Jason D., MS</au><au>Narayan, Sanjiv M., MD, FHRS</au><au>Lalani, Gautam G., MD</au><au>Trayanova, Natalia A., PhD, FHRS, FAHA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling</atitle><jtitle>Heart rhythm</jtitle><addtitle>Heart Rhythm</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>7</volume><issue>8</issue><spage>1093</spage><epage>1101</epage><pages>1093-1101</pages><issn>1547-5271</issn><eissn>1556-3871</eissn><abstract>Background Alternans in action potential voltage (APV-ALT) at heart rates <110 bpm is a novel index to predict ventricular arrhythmias. However, the rate dependency of APV-ALT and its mechanisms in failing versus nonfailing human myocardium are poorly understood. It is hypothesized that APV-ALT in human heart failure (HF) reflects abnormal calcium handling. Objective Using a modeling and clinical approach, our objectives were to (1) determine how APV-ALT varies with pacing rate and (2) ascertain whether abnormalities in calcium handling explain the rate dependence of APV-ALT in HF. Methods APV-ALT was analyzed at several cycle lengths (CLs) using a dynamic pacing protocol applied to a human left ventricle wedge model with various alterations in calcium handling. Modeled APV-ALT was used to predict APV-ALT in left ventricle monophasic action potentials recorded from HF (n = 3) and control (n = 2) patients with the same pacing protocol. Results Reducing the sarcoplasmic reticulum calcium uptake current ≤25%, the release current ≤11%, or the sarcolemmal L-type calcium channel current ≤43% of control predicted APV-ALT to arise at CL ≥600 ms and then increase in magnitude by >400% for CL <400 ms. In HF patients, APV-ALT arose at CL = 600 ms and then increased in magnitude by >500% at CL <350 ms. For all other model alterations and for control patients, APV-ALT occurred only at CL <500 ms. Conclusions APV-ALT shows differing rate dependence in HF versus control patients, arising at slower rates in HF and predicted by models with abnormal calcium handling. Future studies should investigate whether APV-ALT at slow rates identifies patients with deranged calcium handing, including HF patients before decompensation or at risk for arrhythmias.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20382266</pmid><doi>10.1016/j.hrthm.2010.04.008</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Action potential alternans Action Potentials - physiology Aged Arrhythmias, Cardiac - etiology Arrhythmias, Cardiac - physiopathology Calcium - metabolism Calcium handling Calcium Metabolism Disorders - complications Calcium Metabolism Disorders - physiopathology Cardiac Pacing, Artificial Cardiovascular Computer modeling Heart failure Heart Failure - complications Heart Failure - physiopathology Heart Rate - physiology Humans Middle Aged Models, Cardiovascular |
| title | Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling |
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