Published Online
on November 11, 2002

A more recent version of this article appeared on December 3, 2002

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Submitted on July 11, 2002
Revised on September 13, 2002
Accepted on September 13, 2002

Effects of Selective ₁- and ₂-Adrenergic Blockade on Coronary Flow Reserve After Coronary Stenting

Luisa Gregorini MD^*, Jean Marco MD, Bruno Farah MD, Monique Bernies MD, Carlo Palombo MD, Michaela Kozàkovà MD, Irene M. Bossi MD, Bernard Cassagneau MD, Jean Fajadet MD, Carlo Di Mario MD, Remo Albiero MD, Massimo Cugno MD, Adalberto Grossi MD, and Gerd Heusch MD

From Clinique Pasteur (J.M., B.F., M.B., I.M.B., B.C., J.F.), Centre de Cardiologie Interventionelle, Toulouse, France; Experimental Surgery and Transplantation Institute, Ospedale Maggiore IRCCS, University of Milano (L.G., M.C., A.G.); Centro Cuore Columbus (L.G., C.D.M., R.A.), Milano; Clinical Physiology Institute (C.P., M.K.), University of Pisa, Italy; and Institut für Pathophysiologie (G.H.), Universitätsklinikum, Essen, Germany.

^* To whom correspondence should be addressed. E-mail: Luisa.Gregorini{at}unimi.it.

Background—Coronary flow reserve (CFR) is not normalized shortly after coronary stenting. We hypothesized that -adrenergic coronary vasoconstriction acts to limit CFR.

Methods and 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 µg IC or 140 µg/kg per minute IV) before and after stenting. Finally, either the ₁-antagonist urapidil (10 mg IC) or the 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 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.

Key words: adenosine • blood flow • microcirculation • nervous system, sympathetic • receptors, adrenergic, alpha

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