Tetrahydrobiopterin increases myocardial blood flow in healthy volunteers:a double-blind, placebo-controlled study

Objectives: Tetrahydrobiopterin (BH4) is a regulatory cofactor for the acti vity of nitric oxide synthases. Vasodilating properties of BH4 have been re ported 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 MB F in healthy volunteers. Methods and Results: Resting MBF was assessed in 15 subjects receiving eith er intravenous BH4 (10 mg/kg) or placebo using positron emission tomography (PET) and [N-13]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 (no n-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 gro ups. BH4 was very well tolerated. Conclusion: Systemically administered BH4 is safe and effectively increases resting MBF in health volunteers.