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Am J Physiol Heart Circ Physiol 273: H2708-H2720, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 6, H2708-H2720, December 1997

Relaxation effect of CGP-48506, EMD-57033, and dobutamine in ejecting and isovolumically beating rabbit hearts

Bryan K. Slinker, Henry W. Green III, Yiming Wu, Robert D. Kirkpatrick, and Kenneth B. Campbell

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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