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Am J Physiol Heart Circ Physiol 278: H313-H320, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 2, H313-H320, February 2000

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

Taketo Tanigawa, Masafumi Yano, Michihiro Kohno, Takeshi Yamamoto, Takayuki Hisaoka, Kaoru Ono, Takeshi Ueyama, Shigeki Kobayashi, Yuhji Hisamatsu, Tomoko Ohkusa, and Masunori Matsuzaki

Second Department of Internal Medicine, Yamaguchi University School of Medicine, 1144 Kogushi, Ube, Yamaguchi 755-8505, Japan

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 Ca2+-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 µg · kg-1 · min-1) or by milrinone (4-20 µg/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). Ca2+-ATPase activity increased similarly in HF and control with dobutamine (1 µM; +11% in HF vs. +12% in control, P = NS), whereas it increased more with milrinone (1 µM; +19% in HF vs. +11% in control, P < 0.05). Ca2+-ATPase activity-cAMP relationships were shifted to the left by milrinone or dobutamine in HF compared with control. Thus, in HF, the sensitivity of Ca2+-ATPase activity to cAMP was increased on addition of cAMP-dependent inotropic agents, contributing to the preservation of positive lusitropy.

calcium; calcium-adenosinetriphosphatase; dobutamine; milrinone; sarcoplasmic reticulum


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