Effects of therapeutic doses of human atrial natriuretic peptide on load and myocardial performance in patients with congestive heart failure

Abstract

The benefits of atrial natriuretic peptide (ANP) in patients with congestive heart failure (CHF) have been demonstrated. However, the myocardial actions of ANP remain unclear. Using relatively load-insensitive left ventricular pressure-volume analysis, the myocardial and load-altering actions of ANP in patients with moderate CHF were studied. After obtaining steady-state data using micromanometers and conductance catheters, ANP was infused in 9 patients with CHF at 0.01 and 0.1 μg/kg/min for 30 minutes, respectively. Hemodynamic variables, plasma ANP, and cyclic guanosine monophosphate (cGMP) levels were determined before and 30 minutes after each ANP infusion. ANP at 0.01 μg/kg/min increased plasma ANP and cGMP levels from 73 ± 34 to 139 ± 34 pg/ml and from 4 ± 1 to 8 ± 2 pmol/ml, respectively. ANP infusion caused a significant decrease in end-systolic pressure without any changes in heart rate. End-diastolic pressure was significantly decreased but there was no significant change in left ventricular end-diastolic volume. The time constant for isovolumetric relaxation was decreased. ANP infusion at 0.1μg/kg/min caused further decreases in end-systolic pressure, end-diastolic pressure and volume, and the time constant for isovolumetric relaxation (p <0.05) without any changes in heart rate. The slope of the end-systolic pressure-volume relation was increased from 1.3 ± 0.2 to 1.6 ± 0.3 mm Hg/ml (p <0.05), indicating increased contractility. Plasma ANP and cGMP levels were increased to 422 ± 44 pg/ml and 16 ± 3 pmol/ml, respectively. Thus, ANP infusion increased cGMP generation, decreased afterload and preload, and improved left ventricular systolic and diastolic function.