Effects of selective alpha1- and alpha2-adrenergic blockade on coronary flow reserve after coronary stenting.
BACKGROUND
Coronary flow reserve (CFR) is not normalized shortly after coronary stenting. We hypothesized that alpha-adrenergic coronary vasoconstriction acts to limit CFR.


RESULTS
We assessed flow velocity by Doppler wires and cross-sectional area by angiography in 46 patients undergoing coronary culprit lesion stenting (81+/-4% stenosis). Hyperemia was induced by adenosine (24 micro g IC or 140 micro g/kg per minute IV) before and after stenting. Finally, either the alpha(1)-antagonist urapidil (10 mg IC) or the alpha(2)-antagonist yohimbine (3 mg IC) was randomly combined with adenosine. In 8 subjects with angiographically normal coronary arteries, CFR was increased from 3.21+/-0.30 to 3.74+/-0.43 by yohimbine and to 4.58+/-0.65 by urapidil, respectively (P=0.0001). Patients were divided according to the cutoff of CFR > or =3.0 (n=18) or <2.5 (n=28). Revascularization per se did not change CFR. However, 15 minutes after stenting, CFR decreased to 2.05+/-0.55 from CFR 3.64+/-0.58, whereas in patients with CFR 2.39+/-0.51, it remained unchanged. Yohimbine improved CFR to 3.26+/-0.42 and to 3.41+/-0.58 in patients with >3.0 and <2.05+/-0.55 baseline CFR, respectively. Urapidil improved CFR to 3.52+/-0.30 and 3.98+/-1.07, respectively.


CONCLUSIONS
Urapidil and yohimbine attenuated the CFR impairment occurring after revascularization by increasing both the epicardial vasodilator effect of adenosine and the blood flow velocity, thus suggesting that the adrenergic system plays an important role in limiting the capacity of the coronary circulation to dilate.
Gregorini
Luisa
L
Experimental Surgery and Transplantation Institute, Ospedale Maggiore IRCCS, University of Milano, Italy. Luisa.Gregorini@unimi.it
Marco
Jean
J
Farah
Bruno
B
Bernies
Monique
M
Palombo
Carlo
C
Kozàkovà
Michaela
M
Bossi
Irene M
IM
Cassagneau
Bernard
B
Fajadet
Jean
J
Di Mario
Carlo
C
Albiero
Remo
R
Cugno
Massimo
M
Grossi
Adalberto
A
Heusch
Gerd
G
D000241:Adenosine / Q000009:adverse effects; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D015607:Stents; D014654:Vascular Patency / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D015016:Yohimbine; C015568:urapidil; D000241:Adenosine