Examination of the in vivo cardiac electrophysiological effects of nesiritide (human brain natriuretic peptide) in conscious dogs.
BACKGROUND
Human brain natriuretic peptide (hBNP) is a new therapeutic agent, nesiritide, indicated in patients with decompensated congestive heart failure, a group at significant risk of developing cardiac arrhythmias. Whether hBNP has cardiac electrophysiologic effects has not been reported.


RESULTS
In 9 healthy, chronically instrumented, conscious dogs, hemodynamic and electrophysiologic parameters were assessed at baseline and during recombinant hBNP (nesiritide) infusion at 0.03 and 0.09 microg/kg/min after 1 hour at each dose. Infusion of hBNP produced dose-related increases (P <.001) in hBNP and cyclic GMP plasma levels and reductions (P <.05) in mean arterial pressure. Mean central venous pressure and sinus cycle length did not change significantly. Infusion of hBNP produced no significant changes in any of the electrophysiologic parameters including no change in surface ECG variables (P wave duration, PR interval, QRS duration, and QTc interval), corrected sinus node recovery time, atrioventricular nodal Wenckebach cycle length, and atrial and ventricular effective refractory periods measured at a 400 ms cycle length. Spontaneous or induced arrhythmias were not observed during hBNP infusion.


CONCLUSIONS
In conscious, healthy dogs, short-term infusion of recombinant hBNP has no significant effects on atrial or ventricular electrophysiologic parameters.
Fenelon
Guilherme
G
Department of Medicine, West Roxbury Veterans Affairs Medical Center, Harvard Medical School, West Roxbury, Massachusetts, USA.
Protter
Andrew A
AA
Stambler
Bruce S
BS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D003243:Consciousness / Q000502:physiology*; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D023421:Models, Animal; D008955:Models, Cardiovascular; D045283:Natriuretic Agents / Q000502:physiology*; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects / Q000494:pharmacology*; D012016:Reference Values; D016896:Treatment Outcome; D016276:Ventricular Function
D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain; D006152:Cyclic GMP