L-arginine improves diminished cerebral CO2 reactivity in patients

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.

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 L-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%).

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.

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.