Does the beta-blocker nebivolol increase coronary flow reserve?
BACKGROUND
Nebivolol, a highly selective beta1-adrenergic receptor-blocker, increases basal and stimulated endothelial nitric oxide (NO)-release. It is unknown, whether coronary perfusion is improved by the increase in NO availability. Therefore, we sought to evaluate the effect of nebivolol on coronary flow reserve (CFR) and collateral flow.


METHODS
Doppler-flow wire derived coronary flow velocity measurements were obtained in ten controls and eight patients with coronary artery disease (CAD) at rest and after intracoronary nebivolol. CFR was defined as maximal flow during adenosine-induced hyperemia divided by resting flow. In the CAD group, collateral flow was determined after dilatation of a flow-limiting coronary stenosis. Collateral flow index (CFI) was defined as the ratio of flow velocity during balloon inflation divided by resting flow.


RESULTS
CFR at rest was 3.0+/-0.6 in controls and 2.1+/-0.4 in CAD patients. After intracoronary doses of 0.1, 0.25, and 0.5 mg nebivolol, CFR increased to 3.4+/-0.7, 3.9+/-0.9, and 4.0+/-0.1 (p<0.01) in controls, and to 2.3+/-0.7, 2.6+/-0.9, and 2.6+/-0.5 (p<0.05) in CAD patients. CFI decreased significantly with intracoronary nebivolol and correlated to changes in heart rate (r=0.75, p<0.001) and rate-pressure product (r=0.59, p=0.001).


CONCLUSIONS
Intracoronary nebivolol is associated with a significant increase in CFR due to reduction in resting flow (controls), or due to an increase in maximal coronary flow (CAD patients). CFI decreased with nebivolol parallel to the reduction in myocardial oxygen consumption.
Togni
Mario
M
Swiss Cardiovascular Center Bern, Inselspital, CH-3010 Bern, Switzerland. mario.togni@insel.ch
Vigorito
Francesco
F
Windecker
Stephan
S
Abrecht
Linda
L
Wenaweser
Peter
P
Cook
Stephane
S
Billinger
Michael
M
Meier
Bernhard
B
Hess
Otto M
OM
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D015906:Angioplasty, Balloon, Coronary; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D015150:Echocardiography, Doppler; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol