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CLINICAL STUDY

Subcutaneous administration of brain natriuretic peptide in experimental heart failure

Manuscript received January 14, 2000; revised manuscript received April 23, 2000, accepted June 19, 2000.

Reprint requests and correspondence: Dr. Horng H. Chen, Cardiorenal Research Laboratory, Guggenheim 915, Mayo Clinic and Foundation, 200 First Street Southwest, Rochester, Minnesota 55905
chen.horng{at}mayo.edu

OBJECTIVES

The objective of this investigation was to define for the first time the cardiorenal and humoral actions of repeated short-term administration of subcutaneous (SQ) brain natriuretic peptide (BNP) administration during the evolution of experimental heart failure.

BACKGROUND

The rationale of this study was based on BNP as a vasodilating, natriuretic, renin-inhibiting and lusitropic peptide of cardiac origin.

METHODS

First, we defined the cardiorenal and humoral responses to acute low and high dose (5 µg/kg or 25 µg/kg) of SQ BNP in experimental heart failure to establish the acute efficacy of an SQ delivery. Second, we characterized the response to 10 days of repeated short-term administration of BNP during the evolution of experimental heart failure produced by rapid ventricular pacing.

RESULTS

Plasma BNP and 3',5'-cyclic guanosine monophosphate rapidly increased and peaked at 30 min after acute SQ BNP administration with increases in urinary sodium excretion, urine flow and renal blood flow in association with reductions in cardiac filling pressures. After 10 days of repeated short-term administration of SQ BNP, cardiac output was increased and systemic vascular resistance and pulmonary capillary wedge pressure were decreased, as compared with untreated dogs with heart failure.

CONCLUSIONS

This study demonstrated for the first time that repeated short-term administration of SQ BNP administration for 10 days during the evolution of left ventricular dysfunction in a canine model results in an improvement in cardiovascular hemodynamics. This investigation supports a potential novel strategy for the chronic administration of BNP in the therapeutics of heart failure.

Abbreviations and Acronyms   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   cGMP = 3',5'-cyclic guanosine monophosphate   CHF = congestive heart failure   CLLi = lithium clearance   CO = cardiac output   DFNaR = distal fractional reabsorption of sodium   GFR = glomerular filtration rate   MAP = mean arterial pressure   PAP = pulmonary artery pressure   PCWP = pulmonary capillary wedge pressure   PFNaR = proximal fractional reabsorption of sodium   RAP = right atrial pressure   RBF = renal blood flow   RIA = radioimmunoassay   RVR = renal vascular resistance   SQ = subcutaneous or subcutaneously   SVR = systematic vascular resistance   UcGMPV = urinary cGMP excretion   UNaV = urine sodium excretion

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