Relaxation effect of CGP-48506, EMD-57033, and dobutamine in ejecting and isovolumically beating rabbit hearts.
Because it is not known whether ejection influences the negative effect of the Ca(2+)-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 Ca(2+)-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 x 10(-6) M EMD-57033, the negligible lusitropic effect of 6 x 10(-6) M CGP-48506, and the positive lusitropic effect of 1.25 x 10(-6) M dobutamine. Furthermore, comparison of the effect of the two Ca(2+)-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.
Slinker
B K
BK
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520, USA.
Green
H W
HW
Wu
Y
Y
Kirkpatrick
R D
RD
Campbell
K B
KB
D000818:Animals; D001392:Azocines / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008433:Mathematics; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D012044:Regression Analysis; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D013829:Thiadiazines / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D001392:Azocines; D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; C095056:BA 41899; D004280:Dobutamine