Background: B-type natriuretic peptide (BNP) is a 32 amino acid cardiac peptide with anti-fibrotic, lusitropic and aldosterone-inhibiting properties mediated by the second messenger cGMP. A limiting property of conventional doses of BNP is excessive hypotension.
Methods: We completed a proof of concept study to determine tolerability and biological activity of IV BNP at two low doses, 0.003 and 0.006 μg/Kg/min, without bolus started within 24 hours of successful reperfusion for anterior AMI. A total of 24 patients were randomly assigned to receive 0.003 (n=12) or 0.006 (n=12) μg/kg/min of IV BNP for 72 hours in addition to standard care during hospitalization for anterior AMI.
Results: Baseline characteristics were similar between both groups. Infusion of BNP at 0.006μg/kg/min resulted in a greater biological activity as measured by higher plasma cGMP levels (8.6±1 vs 5.5±1 pmol/ml, p<0.05) as compared to 0.003 μg/kg/min and suppression of plasma aldosterone (8.0±2 to 4.6±1 ng/ml, P<0.05) which was not observed in the 0.003 group. This increased biological activity was associated with improvement in LV ejection fraction (LVEF) from baseline to 1 month (40±4 to 54±5%, p<0.05) and a decrease of LV end systolic volume index (61±9 to 43±8 ml/m2, p<0.05) at 1 month in 0.006 group but not in the 0.003 group.
Conclusions: This proof of concept pilot study demonstrates that 72 hour infusion of low BNP at the time of anterior AMI is well tolerated and is biologically active, specifically, patients had improved LVEF and smaller LV end systolic volume at 1 month.
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