| Beneficial effects of the Ca2+ sensitizer EMD 57033 in exercising pigs with infarction-induced chronic left ventricular dysfunction. | |
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MedLine Citation:
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PMID: 11588109 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. It is unknown how cardiac stimulation by Ca(2+) sensitization modulates the cardiovascular response to exercise when left ventricular (LV) function is chronically depressed following a myocardial infarction. We therefore investigated the effects of EMD 57033 at rest and during exercise and compared these to those of the mixed Ca(2+)-sensitizer/phosphodiesterase-III inhibitor pimobendan. 2. Pigs were chronically instrumented for measurement of cardiovascular performance. At the time of instrumentation, infarction was produced by coronary artery ligation (MI, n=12). Studies in MI were performed in the awake state, 2 - 3 weeks after infarction. 3. MI were characterized by a lower resting cardiac output (18%), stroke volume (30%) and LVdP/dt(max) (18%), and a doubling of LV end-diastolic pressure, compared to normal pigs (N, n=13). 4. In 11 resting MI, intravenous EMD 57033 (0.2 - 0.8 mg kg(-1) min(-1)) increased LVdP/dt(max) (57+/-5%) and stroke volume (26+/-6%) with no effect on heart rate, LV filling pressure, and myocardial O(2)-consumption, similar to N. 5. In MI, the effects of EMD 57033 (0.4 mg kg(-1) min(-1), IV) on stroke volume and LVdP/dt(max) were maintained during treadmill exercise up to 85% of maximal heart rate, while heart rate was lower compared to control exercise (all P<0.05). In contrast, the effects of EMD57033 gradually waned in N at increasing intensity of exercise. 6. Compared to N, the cardiostimulatory effects of pimobendan (20 microg kg(-1) min(-1), IV) were blunted in MI both at rest and during exercise compared to N. 7. In conclusion, the positive inotropic actions of the Ca(2+) sensitizer EMD 57033 are unmitigated in resting and exercising MI compared to N, while those of the mixed Ca(2+)-sensitizer/phosphodiesterase-III inhibitor pimobendan are blunted. |
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Authors:
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D J Duncker; D B Haitsma; D A Liem; N Heins; R Stubenitsky; P D Verdouw |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 134 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-05 Completed Date: 2001-12-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 553-62 Citation Subset: IM |
Affiliation:
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Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, Rotterdam, The Netherlands. Duncker@tch.fgg.eur.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Cardiotonic Agents / pharmacology* Chronic Disease Exercise Test / drug effects* Female Hemodynamics / drug effects, physiology Male Myocardial Infarction / drug therapy*, physiopathology Pyridazines / pharmacology, therapeutic use Quinolines / pharmacology* Swine Thiadiazines / pharmacology* Ventricular Dysfunction, Left / drug therapy*, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Pyridazines; 0/Quinolines; 0/Thiadiazines; 120223-04-3/EMD 53998; 74150-27-9/pimobendan; 7440-70-2/Calcium |
| Comments/Corrections | |
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