Nesiritide: A recombinant human BNP as a therapy for decompensated heart failure

The rationale for the treatment with various pharmacologic agents administered in the management of both chronic and acute decompensated heart failure (ADHF) are based on our understanding of underlying pathophysiology of the patient’s diseases. Recently, the management of HF has shifted from traditional drugs that are administered to ameliorate the gross hemodynamic manifestations of volume overload and hypoperfusion to the agents that modulate the neurohormonal derangements associated with the failing heart. This change has marked a paradigmatic shift from thinking of HF in the hemodynamic model to understanding the syndrome in terms of neurohormonal activation. Clinicians have offered treatment modalities aimed at addressing the overt hemodynamic imbalance of decompensated HF, namely positive ionotropic agents and parenteral diuretics. Elucidation of the neurohormonal contribution to HF pathophysiology has been a seminal development in understanding the natural history of the syndrome and targeting drug therapy to reduce morbidity and mortality. [1] Neurohormonal stimulation, initially a compensatory mechanism, ultimately leads to cardiac dysfunction. Baroreceptor sensitivity is often down-regulated in HF; even when normal arterial pressures are restored and the sympathetic stimulation is maintained. The major hormones known to be elevated and likely to have the detrimental effects in chronic HF include angiotensin II, aldosterone, norepinephrine, arginine, vasopressin, and endothelin. The natriuretic peptide is a major homeostatic force that counterbalances the vasoconstriction and retentive effects of sustained neurohormonal secretion. [3] Brain natriuretic peptide (BNP) is one of the three natriuretic peptides that are important in maintaining hemodynamic and neurohormonal equilibrium in normal human physiology. The other two (atrial natriuretic peptide – ANP and C-type natriuretic peptide) have coordinated actions with BNP that help maintain adequate vascular volume and pressure in response to volume overload. The BNP is synthesized and released by cardiac myocytes in response to ventricular stretch and volume overload. The correlation of plasma BNP with the severity of HF suggested its use as a biomarker in HF. Although, neurohormonal blockade is becoming a recognized principle in the treatment of chronic HF, this is not routinely implicated in the management of acute heart failure (HF). Nesiritide, a synthetic natriuretic peptide, is the first approved vasoactive agent for management of ADHF. It is a recombinant form of human BNP that is structurally and biochemically identical to endogenously produced BNP (Fig. 1). The BNP is important in hemodynamic and Nesiritide: A recombinant human BNP as a therapy for decompensated heart failure Molecules of