Journal article
Overall Cardiac Functional Effect of Positive Inotropic Drugs with Differing Effects on Relaxation
Journal of cardiovascular pharmacology, Vol.36(1), pp.1-13
07/2000
Handle:
https://hdl.handle.net/2376/113266
PMID: 10892654
Abstract
Recent interest in so-called calcium-sensitizing positive inotropic drugs has highlighted the potential problem of a positive effect on force development being offset, at least partially, by the negative effect that many of these drugs have on relaxation. The purpose of this study was to examine the interplay of contraction and relaxation in determining the overall cardiac effect of different positive inotropic drugs. Using a buffer-perfused isolated rabbit heart preparation, we studied four drugs (calcium, dobutamine, EMD 57033, and CGP 48506) that were given at doses sufficient to increase similarly left ventricular pressure-generating capability by ∼20%. We show that, even though they produce equivalent changes in pressure-generating capability, these four agents produce dissimilar changes in relaxation capability, with dobutamine speeding relaxation, EMD 57033 slowing relaxation, and calcium and CGP 48506 having little effect of relaxation. Similar relative effects were observed for drug-induced changes in the timing of pressure-generation events. These effects combine to produce different drug-induced changes in overall cardiac pump function judged by the relation between cardiac output and heart rate. Dobutamine shifted the maximal cardiac output to a higher heart rate. In contrast, both calcium sensitizers shifted the maximum in cardiac output to a lower heart rate, whereas calcium had no effect. Thus even though positive inotropic drugs may have similar effects on left ventricular pressure generation, the overall benefit of such drugs on ventricular pump function will depend on how the drug also affects ventricular relaxation and ejection capabilities.
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Details
- Title
- Overall Cardiac Functional Effect of Positive Inotropic Drugs with Differing Effects on Relaxation
- Creators
- Bryan Slinker - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington, U.S.AYiming WuHenry GreenRobert KirkpatrickKenneth Campbell
- Publication Details
- Journal of cardiovascular pharmacology, Vol.36(1), pp.1-13
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Lippincott Williams & Wilkins, Inc
- Identifiers
- 99900547305601842
- Language
- English
- Resource Type
- Journal article