Document Detail


Beneficial effects of the Ca2+ sensitizer EMD 57033 in exercising pigs with infarction-induced chronic left ventricular dysfunction.
MedLine Citation:
PMID:  11588109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D J Duncker; D B Haitsma; D A Liem; N Heins; R Stubenitsky; P D Verdouw
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  134     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-05     Completed Date:  2001-12-05     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  553-62     Citation Subset:  IM    
Affiliation:
Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, Rotterdam, The Netherlands. Duncker@tch.fgg.eur.nl
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MeSH Terms
Descriptor/Qualifier:
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:
0/Cardiotonic Agents; 0/Pyridazines; 0/Quinolines; 0/Thiadiazines; 120223-04-3/EMD 53998; 34AP3BBP9T/pimobendan; 7440-70-2/Calcium
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