L-arginine reactivity in cerebral vessels after severe traumatic brain injury

Abstract

Objectives Traumatic brain injury (TBI) causes an early reduction of cerebral blood flow (CBF). The purpose was to study cerebrovascular endothelial function by examining the reactivity of cerebral vessels to L-arginine. Methods Fifty-one patients with severe TBI were prospectively studied by measuring cerebral hemodynamics before and after the administration of L-arginine, 300 mg/kg at 12 hrs and at 48 hrs after injury. These hemodynamic measurements, using transcranial Doppler techniques, included internal carotid flow volume as an estimate of hemispheric cerebral blood flow, flow velocity in intracranial vessels, CO2 reactivity, and dynamic pressure autoregulation using thigh cuff deflation and carotid compression methods. Changes in the hemodynamics with L-arginine administration were analyzed using a general linear mixed model. Results L-arginine produced no change in mean arterial pressure, intracranial pressure, or brain oxygenation. Overall, L-arginine induced an 11.3% increase in internal carotid artery flow volume (p= .0190). This increase was larger at 48 hrs than at 12 hrs (p= .0045), and tended to be larger in the less injured hemisphere at both time periods. The response of flow velocity in the intracranial vessels was similar, but smaller differences with administration of L-arginine were observed. There was a significant improvement in CO2 reactivity with L-arginine, but no change in dynamic pressure autoregulation. Discussion The low response of the cerebral vessels to L-arginine at 12 hrs post-injury with improvement at 48hrs suggests that dysfunction of cerebrovascular endothelium plays a role in the reduced CBF observed after TBI.

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

“…During the early phase, a period of relative deficiency in NO and a low level of CBF, the administration of l -arginine has been shown to improve CBF and neurological outcome in models of TBI ( 34 ). Administration of l -arginine in patients after severe TBI induced an increase in internal carotid artery flow volume, which was larger at 48 h than at 12 h, and tended to be larger in the less injured hemisphere at both time periods, suggesting that dysfunction of cerebrovascular endothelium plays a role in the reduced CBF observed after TBI ( 40 ). Some of the variability in patient outcome that occurs following severe TBI may result from eNOS polymorphisms ( 41 ).…”

Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1–Dependent Uncoupling of Endothelial Nitric Oxide Synthase

“…First, to test the contribution of BH 4 depletion to eNOS uncoupling, we treated arteries with the pterin salvage pathwayderived precursor l-sepiapterin (1 lM). l-sepiapterin partially restored vasodilation induced by ACh; although the EC 50 was not affected, the maximal dilation induced by 1 lM ACh in the presence of l-sepiapterin was improved and reached approximately 90% of control levels ( Fig. 5 and Table 1).…”

“…47,48 Although these observations would seem to suggest l-arginine supplementation as a therapeutic strategy, several studies have shown that l-arginine reactivity varies depending on time point after injury, vascular bed, and species studied, age, and the underlying disease. [48][49][50][51][52][53] One of the limitations of our study is that we focused on a specific time point after injury. Additional studies are needed to address the longitudinal course of vascular responses including earlier times after TBI and later time points after clinical recovery.…”

Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions

“…There was also a significant direct relationship between the concentration of NO metabolites and regional CBF [ 142 ]. In severe TBI patients, l -arginine administration at 48 h post-injury had a better response in improving internal carotid artery flow volume than at 12 h following brain injury [ 143 ]. The above findings further emphasize the importance of determining the effective therapeutic window for drug administration following brain injury.…”