Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure.
In tachycardia-induced heart failure (HF), positive lusitropic effects of milrinone or dobutamine were assessed by evaluating the time constant of left ventricular (LV) pressure decay (tau) and Ca(2+)-ATPase activity of the sarcoplasmic reticulum (SR). The peak value of the positive first derivative of LV pressure (+dP/dt) was less increased, either by dobutamine (2-10 microg x kg(-1) x min(-1)) or by milrinone (4-20 microg/kg), in HF than in control (P < 0.05), whereas tau was shortened to an extent similar to that in control with dobutamine [P = not significant (NS)] and to an even greater extent with milrinone (P < 0.05). Ca(2+)-ATPase activity increased similarly in HF and control with dobutamine (1 microM; +11% in HF vs. +12% in control, P = NS), whereas it increased more with milrinone (1 microM; +19% in HF vs. +11% in control, P < 0.05). Ca(2+)-ATPase activity-cAMP relationships were shifted to the left by milrinone or dobutamine in HF compared with control. Thus, in HF, the sensitivity of Ca(2+)-ATPase activity to cAMP was increased on addition of cAMP-dependent inotropic agents, contributing to the preservation of positive lusitropy.
Tanigawa
T
T
Second Department of Internal Medicine, Yamaguchi University School of Medicine, 1144 Kogushi, Ube, Yamaguchi 755-8505, Japan.
Yano
M
M
Kohno
M
M
Yamamoto
T
T
Hisaoka
T
T
Ono
K
K
Ueyama
T
T
Kobayashi
S
S
Hisamatsu
Y
Y
Ohkusa
T
T
Matsuzaki
M
M
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002303:Cardiac Output, Low / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D020105:Milrinone / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D004280:Dobutamine; D000242:Cyclic AMP; D000252:Calcium-Transporting ATPases; D020105:Milrinone