l -Arginine Improves Diminished Cerebral CO 2 Reactivity in Patients

Abstract

Background and Purpose— There is experimental evidence that l -arginine restores diminished CO 2 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 CO 2 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 CO 2 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% CO 2 . 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 CO 2 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 CO 2 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.