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

Abstract

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/d t) 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/d t 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/d t by 108 ± 8% and MAP by 21 ± 2% and decreased HR by 28 ± 4%, whereas Dob increased LV dP/d t 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.