Effects of Intravenous Nesiritide on Human Coronary Vasomotor Regulation and Myocardial Oxygen Uptake

Abstract

Background-Nesiritide, recombinant human B-type natriuretic peptide, has been shown to be efficacious in the treatment of decompensated heart failure. The effects of intravenous nesiritide on the human coronary vasculature have not been studied. Methods and Results-Ten patients underwent right and left heart catheterization. Baseline coronary blood flow was determined using quantitative coronary angiography (QCA) and an intracoronary Doppler-tipped guidewire. Myocardial oxygen uptake was measured using a coronary sinus catheter. Patients then received an intravenous infusion of nesiritide (2 g/kg bolus followed by 0.01 g/kg per min infusion) for 30 minutes. Right atrial pressure decreased 52% (Pϭ0.012), pulmonary artery mean pressure decreased 19% (Pϭ0.03), pulmonary capillary wedge pressure decreased 46% (Pϭ0.002), and mean arterial pressure decreased 11% (Pϭ0.007). QCA demonstrated a 15% increase in coronary artery diameter from a baseline of 2.6Ϯ0.8 to 3.0Ϯ0.8 mm at 30 minutes (Pϭ0.007). The coronary velocity measure of average peak velocity increased 14% from 20.8Ϯ6.4 at baseline to 23.8Ϯ7.2 cm/s at 5 minutes (Pϭ0.015) and then returned to baseline for the remainder of the infusion. Coronary blood flow increased 35% (Pϭ0.007), whereas coronary resistance decreased 23% at 15 and 30 minutes (Pϭ0.036). Myocardial oxygen uptake decreased 8% during the nesiritide infusion (Pϭ0.043). Conclusions-Nesiritide exerts coronary vasodilator effects on both the coronary conductance and resistance arteries.Despite a decrease in coronary perfusion pressure, coronary artery blood flow is increased, coronary resistance is decreased, and myocardial oxygen uptake is decreased.

Effects of recombinant human brain natriuretic peptide on the prognosis of patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention: a prospective, multi-center, randomized clinical trial

“…Intravenous thrombolysis or PCI shows better therapeutic effects on acute anterior MI. Since previous studies reported that rhBNP can improve negative left ventricular remodeling and protect left ventricular function (17)(18)(19)(20)(21)(22), we presumed that rhBNP use has better therapeutic effects on acute anterior MI than in other infarction sites. Therefore, we investigated whether rhBNP has beneficial effects on this site, and determined its therapeutic intensity.…”

“…BNP is also a natural factor against cardiac remodeling that regulates the levels of cytokines and inflammatory factors through regulating the expression of fibrosis genes. Furthermore, it directly exerts effects on cardiac fibroblasts to reduce the extracellular matrix of myocardial cells and alleviate interstitial fibrosis and myocardial hypertrophy (18)(19)(20)(21). In addition, BNP selectively expands coronary and lung circulation, increases coronary blood flow and reduces the consumption of myocardial oxygen (22).…”

Lack of activation of molecular forms of the BNP system in human grade 1 hypertension and relationship to cardiac hypertrophy

“…natriuretic peptide; brain natriuretic peptide; amino-terminal pro-brain natriuretic peptide; left ventricular hypertrophy BRAIN NATRIURETIC PEPTIDE (BNP) is synthesized in cardiac myocytes as the precursor proBNP, a 108-amino acid peptide (4, 27, 33), and is converted to biologically active peptide BNP32 via a proteolytic cleavage by corin, a type II transmembrane cardiac serine protease (22,38,39). BNP is present in the circulation in two different forms, the biologically active BNP32 that elicits different beneficial cardiorenal and hormonal actions (1,5,8,11,25,26,40) and the amino-terminal portion of BNP (NT-proBNP) that consists of 76 amino acids.In congestive heart failure (CHF) as well as in hypertension (HTN), ventricular cardiomyocytes are progressively recruited to synthesize BNP (24). Whereas initially a successful defensive endocrine response by the heart to preserve cardiorenal homeostasis might occur, a hyporesponsiveness to cardiac peptides, which might contribute in turn to the progression of hypertension, could follow later.…”

“…BNP is present in the circulation in two different forms, the biologically active BNP32 that elicits different beneficial cardiorenal and hormonal actions (1,5,8,11,25,26,40) and the amino-terminal portion of BNP (NT-proBNP) that consists of 76 amino acids.…”

Molecular and physiological effects of nesiritide

“…At 3 h, patients receiving nesiritide had lower PCWP values and decreased dyspnea when compared with controls (14). Finally, both animal (15) and human trials (16) have demonstrated the direct effect of nesiritide infusion on increasing coronary artery blood flow and reducing coronary resistance, ultimately lowering wall stress and myocardial oxygen demands. Additional research will be required to elucidate whether nesiritide is truly a balanced systemic vasodilator.…”