Background and Purpose--There is experimental evidence that L-arginine restores diminished CO₂ reactivity after mild traumatic brain injury in rats. This effect is believed to be mediated by L-arginine-derived nitric oxide, which is a permissive substrate for CO₂ reactivity. To clarify whether these findings can be transferred to the clinical situation and have beneficial effects in patients, we studied the effects of L-arginine on CO₂ reactivity of the cerebral vessels in patients with impaired vasomotor reactivity (VMR) and compared them with patients with normal VMR.

Methods--Twenty-two patients with cardiovascular risk factors and VMR <50% with no extracranial or intracranial stenoses were examined by bilateral transcranial Doppler sonography of the right and left middle cerebral arteries and compared with 20 age- and risk-matched patients with normal VMR (>50%). VMR was tested by 1-minute hyperventilation, followed by a 3-minute inhalation of 5% CO₂. Examinations were performed before and after infusion of 30 g L-arginine over 30 minutes. The 22 patients with reduced VMR (<50%) were compared with 20 patients with normal VMR (>50%).

Results--Initial mean VMR of the 42 patients was 50±12%. There was no difference between the right- and the left-side VMR. In the 22 patients with reduced VMR in the first examination (42±8%), VMR increased significantly after infusion of L-arginine (52±14%, P=0.005). In contrast, values did not change after infusion of L-arginine in the 20 patients with normal VMR (59±8% before versus 59±13% after L-arginine). There was a negative correlation of initial CO₂ vasoreactivity and the percentage of VMR increase after infusion of L-arginine.

Conclusions--Our data support the hypothesis that in humans L-arginine is able to improve impaired CO₂ reactivity of the cerebral vessels. This effect can be found in patients at cardiovascular risk with impaired VMR and might have therapeutic implications in the future.