atrial-natriuretic-factor and Cyanosis

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.. 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 (P=0.02) and 12-fold (P=0.03) 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 (P=0.22). 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 (P<0.0001). Immunohistochemical staining demonstrated decreased ANP and BNP in hypoxic compared with normoxic right atrial tissue. Isolated myocytes also degranulated when incubated with oxytocin (P<0.0001), but there was no difference in oxytocin levels in cyanotic patients compared with control subjects (P=0.49).. 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.

Topics: Adult; Atrial Appendage; Atrial Natriuretic Factor; Body Water; Cell Hypoxia; Cells, Cultured; Cyanosis; Cytoplasmic Granules; Female; Heart Defects, Congenital; Humans; Hypoxia; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxygen; Oxytocin; Secretory Rate

Many adults with cyanotic congenital heart disease are characterized by reduced ventricular filling pressures and decreased systemic oxygen transport. Data from animals suggest that hypoxia can induce synthesis and secretion of atrial natriuretic peptide.. We measured plasma N-terminal (1-98) proatrial natriuretic peptide (proANP) in 26 cyanotic adults and 28 noncyanotic control subjects. Resting arterial oxygen saturation was significantly lower and hemoglobin concentration and hematocrit significantly greater in cyanotic patients than in control subjects (82+/-6 versus 96+/-3%, 19.7+/-2.2 versus 14.7+/-2.1 g/dL, and 59.0+/-8.5% versus 44.3+/-5.2%, respectively, P<.0001 in all cases). Four cyanotic patients had evidence of iron deficiency. Plasma proANP levels were elevated in cyanotic patients compared with control subjects (1828+/-1147 versus 689+/-343 pmol/L, P<.0001). Comparison of resting arterial oxygen saturation and proANP levels demonstrated an inverse linear relationship between the two measures (r=-.70, P<.0001). There was a significant linear relationship between both hemoglobin concentration and hematocrit and proANP levels as well (r=.53, P=.0003 and r=.48, P=.002, respectively). Cyanotic patients had lower mean right atrial pressures than the control subjects (4+/-3 versus 7+/-2 mm Hg, P=.005), and there were inverse logarithmic relationships between proANP levels and systemic cardiac index (r=-.82, P=.0002), systemic oxygen transport (r=-.68, P=.005), and mixed venous oxygen saturation (r=-.79, P<.0001).. Adults with cyanotic congenital heart disease are characterized by increased levels of plasma proANP. The increased atrial natriuretic peptide most likely results in extracellular and plasma volume depletion and reduced systemic oxygen transport. Measures designed to increase ventricular filling may improve quality of life of these patients.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Cyanosis; Echocardiography, Doppler; Female; Heart Defects, Congenital; Hemodynamics; Humans; Male; Middle Aged; Oxygen; Peptide Fragments; Protein Precursors; Regression Analysis; Stroke Volume