Tetrahydrobiopterin increases myocardial blood flow in healthy volunteers: a double-blind, placebo-controlled study.
OBJECTIVE
Tetrahydrobiopterin (BH4) is a regulatory cofactor for the activity of nitric oxide synthases. Vasodilating properties of BH4 have been reported in vitro and in vivo. The influence of BH4 on myocardial blood flow (MBF), however, is largely unknown. We therefore performed a double-blind, placebo-controlled study to investigate the effect of intravenous BH4 on MBF in healthy volunteers.


RESULTS
Resting MBF was assessed in 15 subjects receiving either intravenous BH4 (10 mg/kg) or placebo using positron emission tomography (PET) and [13N]ammonia. From a mean baseline MBF of 0.91 +/- 0.09 ml/min/g, MBF increased to 1.18 +/- 0.10 ml/min/g after BH4 (n = 10; p = 0.0042). In contrast, in the group receiving placebo mean MBF remained unchanged (non-significant decrease from 0.97 +/- 0.19 to 0.84 +/- 0.11 ml/min/g; n = 5; p = 0.36). Systemic haemodynamics and ECGs remained unaffected in both groups. BH4 was very well tolerated.


CONCLUSIONS
Systemically administered BH4 is safe and effectively increases resting MBF in healthy volunteers.
Walter
R
R
Department of Medicine, Medical Clinic B Research Unit, University Hospital of Zürich, Switzerland.
Kaufmann
P A
PA
Buck
A
A
Berthold
T
T
Wyss
C
C
von Schulthess
G K
GK
Schaffner
A
A
Schoedon
G
G
D000328:Adult; D001708:Biopterins / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012016:Reference Values; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed
D001708:Biopterins; C003402:sapropterin