Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure

Atrial natriuretic peptide (ANP) has potent vasodilatory and natriuretic ac tions and may have therapeutic benefit in congestive heart failure (CHF). T hese benefits may be offset by a negative inotropic effect of ANP seen in i solated preparations. However, ANP's integrated effect on left ventricular (LV) contraction and relaxation, independent of loading conditions, both un der normal conditions and after CHF, is not known. We studied six conscious dogs, instrumented to measure LV and left atrial pressures and to determin e LV volume from three dimensions. ANP produced significant (P < .05) decre ases in LV end-systolic pressure (101.2 +/- 11.8 versus 91.7 +/- 11.2 mm Hg , P < .05) in normal dogs and in dogs with CHF (93.1 +/- 6.4 versus 87.1 +/ - 4.4 mm Hg, P < .05). ANP also caused significant reductions of the slope of end-systolic pressure-end-systolic volume relation both before (7.0 +/- 1.5 versus 6.3 +/- 1.5 mm Hg/ml) and after CHF (4.8 +/- 1.3 versus 4.4 +/- 1.2 mm Hg/ml, P < .05). Both before and after CHF, ANP slowed LV relaxation at matched end-systolic pressure. Before CHF, steady-state stroke volume a nd peak LV filling rate (dV/dt(max)) were reduced. However, after CHF, the fall in end-systolic pressure more than offset the load-independent LV depr ession, as stroke volume, the rate LV relaxation, and dV/dt(max) were incre ased and minimum LV pressure reduced. ANP has negative effects on LV contra ctility and relaxation both before and after CHF. However, after CHF, after load reduction with ANP overcomes its negative effects, resulting in net im provement of LV ejection and relaxation. Thus, the direct cardiodepressant effects of ANP should not limit its usefulness in CHF.