Effects of beta-blockade on neurohumoral responses and neurochemical markers in pacing-induced heart failure.
We investigated neurohumoral profiles and transmitter and neuroenzyme markers of cardiac autonomic innervation in control (unpaced) dogs and three groups of dogs with pacing-induced heart failure (paced, paced + beta-adrenergic blockade, and paced + cardiac denervation). Left ventricular ejection fraction decreased significantly and to a comparable extent in all paced groups. Pacing increased plasma norepinephrine (NE); increases in NE were not attenuated but instead tended to be exaggerated by treatment with propranolol or cardiac denervation. Atrial hypertrophy occurred in all paced groups compared with the control group. However, atrial and right ventricular hypertrophy were not as pronounced in the paced plus cardiac denervation group as in the paced and paced plus propranolol groups. Pacing also depleted neuropeptide Y and NE from all heart chambers; propranolol treatment did not modify these local tissue changes. Pacing caused selective depletion of neuroenzymes predominantly in the left ventricle; again, propranolol did little to modify these changes. In this study of paced animals with experimentally maintained cardiac dysfunction, failure to modify noradrenergic responses with intrapericardial cardiac denervation suggests that noncardiac sources contribute predominantly to high plasma NE. Failure to modify neurohumoral, neuropeptide, and neuroenzyme responses with beta-antagonist suggests this treatment has little practical direct influence on sympathetic vasomotor activity or neuronal function in heart failure.
Levett
J M
JM
Veterans Affairs Medical Center, Iowa City, Iowa.
Marinelli
C C
CC
Lund
D D
DD
Pardini
B J
BJ
Nader
S
S
Scott
B D
BD
Augelli
N V
NV
Kerber
R E
RE
Schmid
P G
PG
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001639:Bicarbonates / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D004285:Dogs; D004558:Electric Stimulation; D004573:Electrolytes / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology*; D009121:Muscle Denervation; D009478:Neuropeptide Y / Q000097:blood; D009479:Neuropeptides / Q000097:blood*; D009638:Norepinephrine / Q000097:blood*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011433:Propranolol / Q000494:pharmacology*; D012016:Reference Values; D012119:Respiration / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D001639:Bicarbonates; D015415:Biomarkers; D004573:Electrolytes; D009478:Neuropeptide Y; D009479:Neuropeptides; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor; D011433:Propranolol; D010100:Oxygen; D009638:Norepinephrine