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      Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure.

      American Journal of Physiology - Heart and Circulatory Physiology
      Animals, Calcium-Transporting ATPases, metabolism, Cardiac Output, Low, physiopathology, ultrasonography, Cardiotonic Agents, pharmacology, Cyclic AMP, Dobutamine, Dogs, Dose-Response Relationship, Drug, Echocardiography, Female, Hemodynamics, drug effects, Male, Milrinone, Myocardial Contraction, Myocardium, Ventricular Function, Left

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          Abstract

          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.

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