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Am J Physiol Heart Circ Physiol 275: H2219-H2226, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 6, H2219-H2226, December 1998

Lack of desensitization and enhanced efficiency of calcium channel promoter in conscious dogs with heart failure

Kuniya Asai, Masami Uechi, Naoki Sato, Weiqun Shen, Tomomi Meguro, Michael A. Mathier, Richard P. Shannon, and Stephen F. Vatner

Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212

The goal of this study was to compare responses to a calcium promoter, BAY y 5959, and dobutamine (Dob) in heart failure (HF). Dogs (n = 9) were chronically instrumented and studied in the conscious state before and after pacing-induced HF. In the control state, BAY y 5959 (20 µg · kg-1 · min-1) increased the first derivative of left ventricular (LV) pressure (dP/dt) by 83 ± 8% and mean arterial pressure (MAP) by 8 ± 2% and decreased heart rate (HR) by 30 ± 3%. With Dob (10 µg · kg-1 · min-1) LV dP/dt rose similarly (+80 ± 6%), but HR also rose (+25 ± 4%) (P < 0.05 vs. BAY y 5959). After HF developed, BAY y 5959 still increased LV dP/dt by 108 ± 8% and MAP by 21 ± 2% and decreased HR by 28 ± 4%, whereas Dob increased LV dP/dt by only 50 ± 7% (P < 0.05 vs. BAY y 5959) and MAP by 7 ± 3%, and HR did not change (+3 ± 3%) (P < 0.05 vs. BAY y 5959). In HF, cardiac work increased more (P < 0.05) with BAY y 5959 (+105 ± 13%) compared with Dob (+47 ± 11%), yet myocardial oxygen consumption increased similarly with the two drugs. Accordingly, mechanical efficiency increased more (P < 0.05) with BAY y 5959 (+73 ± 14%) than with Dob (+17 ± 12%). These data indicate that 1) increases in contractility mediated directly by Ca2+ are relatively resistant to desensitization in HF; and 2) the calcium-channel promoter can produce increases in myocardial contractility and cardiac work similar to those of Dob at a significantly lower oxygen cost, thereby enhancing mechanical efficiency in HF.

catecholamine; myocardial contractility; inotropic agents; myocardial oxygen consumption; myocardial efficiency


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