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Type: Journal article
Title: Coronary β₂-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study
Other Titles: Coronary beta(2)-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study
Author: Puri, R.
Liew, G.
Nicholls, S.
Nelson, A.
Leong, D.
Carbone, A.
Copus, B.
Wong, T.
Beltrame, J.
Worthley, S.
Worthley, M.
Citation: European Heart Journal, 2012; 33(4):495-504
Publisher: W B Saunders Co Ltd
Issue Date: 2012
ISSN: 0195-668X
Statement of
Rishi Puri, Gary Y.H. Liew, Stephen J. Nicholls, Adam J. Nelson, Darryl P. Leong, Angelo Carbone, Barbara Copus, Dennis T.L. Wong, John F. Beltrame, Stephen G. Worthley, and Matthew I. Worthley
Abstract: AIMS: The interaction between coronary β(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary β(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. METHODS AND RESULTS: In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 μg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 μg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 μg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 μg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 μg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.
Keywords: salbutamol; b2-adrenoreceptors; IVUS; endothelial function; atherosclerosis
Rights: © The Author 2011
RMID: 0020117075
DOI: 10.1093/eurheartj/ehr359
Appears in Collections:Medicine publications

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