| Experimental conditions are important determinants of cardiac inotropic effects of propofol. | |
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MedLine Citation:
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PMID: 16249677 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The rationale for this study is that the depressant effect of propofol on cardiac function in vitro is highly variable but may be explained by differences in the temperature and stimulation frequency used for the study. Both temperature and stimulation frequency are known to modulate cellular mechanisms that regulate intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity in cardiac muscle. The authors hypothesized that temperature and stimulation frequency play a major role in determining propofol-induced alterations in [Ca2+]i and contraction in individual, electrically stimulated cardiomyocytes and the function of isolated perfused hearts. METHODS: Freshly isolated myocytes were obtained from adult rat hearts, loaded with fura-2, and placed on the stage of an inverted fluorescence microscope in a temperature-regulated bath. [Ca2+]i and myocyte shortening were simultaneously measured in individual cells at 28 degrees or 37 degrees C at various stimulation frequencies (0.3, 0.5, 1, 2, and 3 Hz) with and without propofol. Langendorff perfused hearts paced at 180 or 330 beats/min were used to assess the effects of propofol on overall cardiac function. RESULTS: At 28 degrees C (hypothermic) and, to a lesser extent, at 37 degrees C (normothermic), increasing stimulation frequency increased peak shortening and [Ca2+]i. Times to peak shortening and rate of relengthening were more prolonged at 28 degrees C compared with 37 degrees C at low stimulation frequencies (0.3 Hz), whereas the same conditions for [Ca2+]i were not altered by temperature. At 0.3 Hz and 28 degrees C, propofol caused a dose-dependent decrease in peak shortening and peak [Ca2+]i. These changes were greater at 28 degrees C compared with 37 degrees C and involved activation of protein kinase C. At a frequency of 2 Hz, there was a rightward shift in the dose-response relation for propofol on [Ca2+]i and shortening at both 37 degrees and 28 degrees C compared with that observed at 0.3 Hz. In Langendorff perfused hearts paced at 330 beats/min, clinically relevant concentrations of propofol decreased left ventricular developed pressure, with the effect being less at 28 degrees C compared with 37 degrees C. In contrast, only a supraclinical concentration of propofol decreased left ventricular developed pressure at 28 degrees C at either stimulation frequency. CONCLUSION: These results demonstrate that temperature and stimulation frequency alter the inhibitory effect of propofol on cardiomyocyte [Ca2+]i and contraction. In isolated cardiomyocytes, the inhibitory effects of propofol are more pronounced during hypothermia and at higher stimulation frequencies and involve activation of protein kinase C. In Langendorff perfused hearts at constant heart rate, the inhibitory effects of propofol at clinically relevant concentrations are more pronounced during normothermic conditions. |
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Authors:
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Noriaki Kanaya; Brad Gable; Peter J Wickley; Paul A Murray; Derek S Damron |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 103 ISSN: 0003-3022 ISO Abbreviation: Anesthesiology Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-26 Completed Date: 2006-01-25 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 1026-34 Citation Subset: AIM; IM |
Affiliation:
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Division of Anesthesiology, The Cleveland Clinic Foundation, Ohio 44195, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Intravenous
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pharmacology* Animals Calcium Signaling / drug effects Cardiotonic Agents* Cell Separation Electric Stimulation Enzyme Inhibitors / pharmacology Heart Ventricles / cytology, drug effects, metabolism Male Myocardial Contraction / drug effects Myocytes, Cardiac / drug effects, metabolism Propofol / pharmacology* Protein Kinase C / antagonists & inhibitors Rats Rats, Sprague-Dawley Temperature |
| Grant Support | |
ID/Acronym/Agency:
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HL-38291/HL/NHLBI NIH HHS; HL-65701/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Intravenous; 0/Cardiotonic Agents; 0/Enzyme Inhibitors; 2078-54-8/Propofol; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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