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Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington 99164-6520
Because it is not known whether ejection
influences the negative effect of the
Ca2+-sensitizing drugs on
ventricular relaxation, we extended our previous analysis of
stress-dependent relaxation in isovolumic beats to encompass ejecting
beats and evaluated the relationships between both the time of onset of
relaxation and the rate of relaxation and wall stress in a broader
analysis framework. Furthermore, because the sites of action of the
Ca2+-sensitizing drugs CGP-48506
and EMD-57033 may be different, and thus CGP-48506 may have fewer
adverse effects on resting muscle length or force, we compared these
two drugs to test the hypothesis that CGP-48506 would have less effect
than EMD-57033 on relaxation in the isolated buffer-perfused rabbit
heart. This analysis of stress-dependent relaxation in both
ejecting and isovolumic beats readily differentiates between the
negative lusitropic effect of 2 × 10
6 M EMD-57033, the
negligible lusitropic effect of 6 × 10
6 M CGP-48506, and the
positive lusitropic effect of 1.25 × 10
6 M dobutamine.
Furthermore, comparison of the effect of the two Ca2+-sensitizing drugs in ejecting
versus isovolumic contractions shows that CGP-48506 affects relaxation
differently in ejecting contractions than it does in isovolumic
contractions, whereas EMD-57033 affects relaxation similarly in both
ejecting and isovolumic contractions.
calcium sensitizer; contraction duration; ventricular relaxation
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