Different patterns of angiotensin II and atrial natriuretic peptide secretion in a sheep model of atrial fibrillation.
BACKGROUND
It is well established that rapid atrial rates, as in atrial fibrillation (AF), cause atrial electrical and structural remodeling leading to the maintenance of AF. The role of neurohumoral changes in this pathophysiologic vicious circle remains unclear.


RESULTS
We followed the concentrations of angiotensin II (AT II) and atrial natriuretic peptide (ANP) in a sheep model of AF. The sheep were atrially paced at 600 beats/min for 15 weeks. Electrophysiologic study was performed at regular intervals, and venous blood samples were taken. There was a slow increase in the vulnerability for AF. The cumulative incidence of sustained AF was 80% after 15 weeks of pacing. This increased vulnerability for AF was accompanied by atrial electrical remodeling and an increase in atrial pressure. AT II increased rapidly and stayed elevated: 17+/-4 pg/mL at baseline, and 40+/-11 and 39+/-7 pg/mL after 1 and 12 weeks of pacing, respectively. ANP rose more progressively: 35+/-7 pg/mL at baseline, and 72+/-17, 95+/-10, and 106+/-23 pg/mL after 1, 3, and 12 weeks, respectively. ANP levels correlated with atrial pressure and inducibility of AF. There was no relation between these parameters and AT II levels.


CONCLUSIONS
AT II and ANP increased significantly in this animal model of AF. Elevation of AT II occurs early and seems to be dependent on rapid atrial rate rather than the presence of AF. ANP increased more progressively. It paralleled the inducibility of AF and atrial stretch. Both neurohumoral pathways may form a potential therapeutic target for treatment of patients with AF.
Willems
R
R
Department of Cardiology, University Hospital Gasthuisberg, University of Leuven, Belgium. Hein.Heidbuchel@uz.kuleuven.ac.be
Sipido
K R
KR
Holemans
P
P
Ector
H
H
Van de Werf
F
F
Heidbüchel
H
H
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D005500:Follow-Up Studies; D006325:Heart Atria / Q000503:physiopathology; D023421:Models, Animal; D012756:Sheep
D000804:Angiotensin II; D009320:Atrial Natriuretic Factor