Increased Atrial and Brain Natriuretic Peptides in Adults With Cyanotic Congenital Heart Disease

Abstract

Background-Brain natriuretic peptide (BNP) levels are used in the evaluation of patients with heart disease, yet there is little understanding of the effect of hypoxia on natriuretic peptide secretion. Furthermore, recent data suggest that oxytocin may mediate stretch-induced atrial natriuretic peptide (ANP) secretion. Methods and Results-Ten patients with cyanotic congenital heart defects and 10 control subjects were studied. N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide levels were 4-fold (Pϭ0.02) and 12-fold (Pϭ0.03) greater in cyanotic patients than in control subjects. Cyanotic patients had reduced body water compared with control subjects, although the difference did not reach statistical significance (Pϭ0.22). In a separate group of patients, cardiac myocytes were isolated from the right atrial appendage during CABG. The amount of oxygen in the buffered saline was varied to simulate hypoxia. Isolated hypoxic atrial myocytes had 43% fewer dense surface secretory granules compared with normoxic myocytes (PϽ0.0001). Immunohistochemical staining demonstrated decreased ANP and BNP in hypoxic compared with normoxic right atrial tissue. Isolated myocytes also degranulated when incubated with oxytocin (PϽ0.0001), but there was no difference in oxytocin levels in cyanotic patients compared with control subjects (Pϭ0.49). Conclusions-ANP and BNP are markedly elevated in adults with cyanotic congenital heart disease despite reduced body water. Our results show that hypoxia is a direct stimulus for ANP and BNP secretion in human cardiac myocytes. These findings may have implications for the interpretation of BNP levels in the assessment of patients with heart and lung disease.

NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension

“…In the current study, patients with other reasons for a high [NT-proBNP] were excluded, and the timing and the conditions surrounding NTproBNP sampling were standardised. A recent study has reported a close relationship between Sv,O 2 and [NT-proBNP] in patients with cyanotic congenital heart disease and PH [49]; however, Sv,O 2 did not predict [NT-proBNP] in the present study, and patients with CHD were specifically excluded. The present authors wish to emphasise that their conclusions can only be applied to selected PH patients assessed in the described manner.…”

Blood N-Terminal proBNP as a Potential Indicator of Cardiac Preload in Patients with High Volume Load

“…Although these values increased in sepsis (Varpula et al 2007), the mechanism for the increase is not clear. This is believed to be related to various causes such as IL-1β , TNF-α (Harada et al 1999;Court et al 2002), IL-6 (Tanaka et al 2004), lipopolysaccharide of Gram-negative bacteria (Tomaru et al 2002), neurosecretory hormones (Ma et al 2005;Clerico et al 2006), hypoxia (Hopkins et al 2004), renal dysfunction, coagulation disorders and the suppression of cardiac muscle (Varpula et al 2007).…”

Circulating levels of pro‐atrial natriuretic peptide in lower respiratory tract infections

“…It is thought that over-secretion of the hormone is caused by hypoxia, leading to pulmonary vasoconstriction, pulmonary hypertension, and right-heart overload [39,40]. Accordingly, exposure of healthy individuals to hypoxia gradually raises circulating ANP levels [41][42][43][44]. Some authors claim that only pulmonary disease including both chronic exposure to hypoxia and pulmonary hypertension, may cause an increase in ANP levels [44].…”