Diastolic function in patients with severe heart failure: Comparison of the effects of enoximone and nitroprusside

To assess whether the phosphodiesterase inhibitor enoximone has a specific, direct effect on left ventricular diastolic function distinct from its inotropic and vasodilator actions, we compared the effects of enoximone and the pure vasodilator nitroprusside in 11 patients with severe heart failure. Mean (± SEM) left ventricular ejection fraction was 0.20 ± 0.03. Simultaneous left ventricular pressure and radionuclide angiographic volume were obtained at baseline, during infusion of nitroprusside, and after intravenous administration of enoximone. Left ventricular end-diastolic pressure (LVEDP) and volume (LVEDV) decreased with both agents (p < .01 vs control); LVEDP was lower for nitroprusside than for enoximone (p < .01) despite a similar LVEDV. Nitroprusside decreased the time constant of exponential left ventricular pressure decay, T(L) (measured by the logarithmic method), from 84 ± 10 to 65 ± 8 msec (p < .01) but had no significant effect on T(D) (measured by the derivative method), maximum negative dP/dt, or the peak rate of early diastolic filling. Enoximone shortened T(L) from 86 ± 12 to 61 ± 9 msec (p < .01) and increased maximum negative dP/dt from 897 ± 101 to 1135 ± 134 mm Hg/sec (p < .01) but did not affect T(D) or the peak filling rate. The left ventricular diastolic pressure-volume relation was shifted downward in only three of 11 patients on nitroprusside and three of 11 patients on enoximone, and these shifts were attenuated by adjusting for simultaneous changes in right atrial pressure. Thus, although nitroprusside and enoximone improved some indexes of early diastolic relaxation, they did not alter T(D) or the peak rate of early diastolic filling. The left ventricular pressure-volume relation was shifted downward, indicating improved overall left ventricular distensibility, in only a minority of patients; the downward shifts resulted in part from a reduction in the external constraints to left ventricular filling. We conclude that enoximone and nitroprusside have similar effects on overall left ventricular diastolic performance in patients with severe heart failure, and, therefore, that enoximone has no specific beneficial effect on diastolic function.