757-5 Hemodynamic Effects of Synthetic Human Brain Natriuretic Peptide Infusion in Patients with Severe Congestive Heart Failure: A Placebo-controlled, Crossover Trial

Brain natriuretic peptide IBNP) and atrial natriuretic peptide (ANP) are naturally-occurring peptide hormones with vasodilating and natriuretic properties, Although the two peptides are structurally similar, the primary site of synthesis, receptor binding properties and metabolic clearance pathways of BNP are distinct from those of AN P. While the plasma concentrations of both BNP and ANP are increased in patients with congestive heart failure (CHF), the biologic significance of this increase is uncertain since the vasodilatory effects of exogenous ANP are attenuated in patients with CHF. To determine if the vasodilating effects of BNP are similarly attenuated in patients with CHF, the acute hemodynamic effects of exogenous synthetic human BNP infusion (Scios Nova) were determined in 10 patients with chronic NYHA Class III congestive heart failure (mean age 55 yrs, mean LVEF 21%) in a doubleblind, placebo-controlled crossover trial. BNP or matching placebo solutions were administered intravenously in 4 incremental doses ranging 0.003-0.1 JLg!kgfmin over 6 hours on two consecutive days. Heart rate (HR). mean arterial pressure (MAP). mean pulmonary artery pressure (PAP). pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured before study drug administration on each day and 60 and 90 minutes after each upward dose increment. Hemodynamic measurements before drug administration and peak hemodynamic responses to administration of human BNP and placebo were as follows:HRMAPPAPPCWPCIBefore Placebo72±981±836±823±52.3±0.3Peak Placebo83±1275±735±821±623±0.3Before BNP72±1185±1038±725±52.1±0.3Peak BNP88±2068±9*22±7*10±5*2,7±0.5†*indicates p<0.01 versus peak placebo†indicates p=0.055 versus peak placeboTwo patients did not tolerate the highest dose of BNP because of transient symptomatic hypotension. In conclusion, short-term intravenous infusion of human BNP acutely improves hemodynamic function in patients with advanced CHF. These findings contrast with previous studies demonstrating attenuated acute hemodynamic effects of exogenous ANP and suggest that the physiologic and pharmacologic roles of these two natriuretic peptide hormones may differ