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

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 chron ically instrumented and studied in the con scious state before and after pa cing-induced HF. In the control state, BAY y 5959 (20 mu g . 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 h eart rate (HR) by 30 +/- 3%. With Dob (10 mu g . kg(-1) . min(-1)) LV dP/dt rose similarly (+80 +/- 6%), but HR also rose (+25 +/- 4%) (P < 0.05 vs. B AY 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 incr eased 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, ca rdiac work increased more (P < 0.05) with BAY y 5959 (+105 +/- 13%) compare d with Dob (+47 +/- 11%), yet myocardial oxygen consumption increased simil arly 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-chan nel 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.