Copyright © 2007, European Society of Cardiology
Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries*
Department of Cardiac Sciences and the Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary AB, Canada
*Corresponding author. Department of Cardiovascular Sciences, Foothills Hospital, 1403 29th Street MW, Calgary, Alberta, Canada, T2N 2T9. Tel.: +1 403 944 1033; fax: +1 403 283 0744. matthew.worthley{at}adelaide.edu.au todd.anderson{at}calgaryhealthregion.ca
Objectives Reduced nitric oxide (NO) bioavailability is a key mechanism in the development of endothelial dysfunction. The NO synthase cofactor, tetrahydrobiopterin (BH4), increases NO availability, yet its effect in the human coronary circulation, particularly following PCI, remains uncertain. This study was designed to evaluate the effects of intracoronary BH4 in human coronary arteries with non-critical coronary artery disease or following percutaneous coronary intervention (PCI).
Methods The study group consisted of 57 stable patients, 10 of which were controls. Active drug was administered in 47 patients, with either de novo non-critical coronary disease (non-stent group; n=25) or following PCI (stent group; n=22). Coronary blood flow (CBF) was measured (0.014-inch Doppler flow wire) in each of these groups in response to sequential intracoronary infusions of acetylcholine (Ach, 10–7 & 10–6 M), BH4 (250 µg/min & 500 µg/min) and a co-infusion of BH4 (500 µg/min) and Ach (10–7 & 10–6 M). The primary endpoint evaluated the % change in CBF to Ach compared to co-infusion of Ach and BH4.
Results Mean age was 60±10 years (M 45:F 12). Regarding the primary hypothesis, no difference was observed between Ach response compared to co-infusion of BH4 and Ach in the % change in CBF in either the non-stent group (Ach 97±122%, Ach/BH4 87±95%) or the stent group (Ach 77±105%, Ach/BH4 55±97%).
Conclusions In native non-critical coronary artery disease or following PCI, coronary microvascular endothelial function is not improved by co-administration of Ach and BH4.
KEYWORDS Nitric oxide; Atherosclerosis; Endothelial function; Angioplasty/coronary intervention
1 Current address: Cardiovascular Investigation Unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia, 5000. Tel.: +61 8 8222 5608; fax: +61 8 8222 2454.
* Dr. Matthew Worthley was supported by a Royal Australasian College of Physician traveling fellowship. Dr. Anderson is a Senior Scholar of the Alberta Heritage Foundation for Medical Research (Edmonton, AB). The study was funded by the Heart and Stroke Foundation of Alberta (TJA).