Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries.
OBJECTIVE
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 microg/min & 500 microg/min) and a co-infusion of BH4 (500 microg/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.
Worthley
Matthew I
MI
Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary AB, Canada. matthew.worthley@adelaide.edu.au
Kanani
Ronak S
RS
Sun
Yi-Hui
YH
Sun
Yichun
Y
Goodhart
David M
DM
Curtis
Michael J
MJ
Anderson
Todd J
TJ
D000109:Acetylcholine / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D015607:Stents; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D014665:Vasodilator Agents; D001708:Biopterins; C003402:sapropterin; D000109:Acetylcholine