TY - JOUR
T1 - Coronary β 2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans
T2 - Novel insights from an in vivo intravascular ultrasound study
AU - Puri, Rishi
AU - Liew, Gary Y H
AU - Nicholls, Stephen J.
AU - Nelson, Adam J.
AU - Leong, Darryl P.
AU - Carbone, Angelo
AU - Copus, Barbara
AU - Wong, Dennis T L
AU - Beltrame, John F.
AU - Worthley, Stephen G.
AU - Worthley, Matthew I.
N1 - Funding Information:
R.P., D.P.L., and G.Y.H.L. are individually supported by a Postgraduate Medical Research Scholarship from the National Health & Medical Research Council (565579, 519177, 497809 respectively). R.P. and D.P.L. are jointly funded by the National Heart Foundation of Australia (PC0804045, PC07A3395) and Dawes Scholarships (Hanson Institute). Equipment funding for this study was obtained from a Cardiovascular Lipid Grant, Pfizer Australia Pty Ltd (CB21.08). M.I.W. is an SA Health Early to Mid Career Practitioner Fellow.
PY - 2012/2
Y1 - 2012/2
N2 - Aims The interaction between coronary β2-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 β2-adrenoreceptors, regional plaque burden and segmental endothelial function.Methods and resultsIn 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 doseresponse 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 SLV 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 SLV or CBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a SLV to IC salbutamol (coefficient-0.18, 95 CI-0.32 to-0.044, P = 0.015). ConclusionsIntracoronary 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.
AB - Aims The interaction between coronary β2-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 β2-adrenoreceptors, regional plaque burden and segmental endothelial function.Methods and resultsIn 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 doseresponse 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 SLV 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 SLV or CBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a SLV to IC salbutamol (coefficient-0.18, 95 CI-0.32 to-0.044, P = 0.015). ConclusionsIntracoronary 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.
KW - IVUS
KW - atherosclerosis
KW - endothelial function
KW - salbutamol
KW - β -adrenoreceptors
UR - http://www.scopus.com/inward/record.url?scp=84857183589&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehr359
DO - 10.1093/eurheartj/ehr359
M3 - Article
C2 - 21951627
AN - SCOPUS:84857183589
VL - 33
SP - 495
EP - 504
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 4
ER -