Trial of the cerebral perfusion response to sodium nitrite infusion in patients with acute subarachnoid haemorrhage using arterial spin labelling MRI

• Published in: Nitric oxide 2024-12, Vol.153, p.50-60
• Main Authors: Ezra, Martyn, Franko, Edit, Spronk, Desiree B., Lamb, Catherine, Okell, Thomas W., Pattinson, Kyle TS
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arterial spin labelling; Cerebral blood flow; Cerebrovascular Circulation - drug effects; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging - methods; Male; Middle Aged; Nitric oxide; Nitric Oxide - administration & dosage; Nitric Oxide - metabolism; Nitrite; Sodium Nitrite - administration & dosage; Sodium Nitrite - pharmacology; Spin Labels; Subarachnoid haemorrhage stroke; Subarachnoid Hemorrhage - diagnostic imaging; Subarachnoid Hemorrhage - drug therapy
• ISSN: 1089-8603; 1089-8611; 1089-8611
• DOI: 10.1016/j.niox.2024.10.003

Aneurysmal subarachnoid haemorrhage (SAH) is a devastating subset of stroke. One of the major determinants of outcome is an evolving multifactorial injury occurring in the first 72 hours, known as early brain injury. Reduced nitric oxide (NO) bioavailability and an associated disruption to cerebral perfusion is believed to play an important role in this process. We sought to explore this relationship, by examining the effect on cerebral perfusion of the in vivo manipulation of NO levels using an exogenous NO donor (sodium nitrite). We performed a double blind placebo controlled randomised experimental medicine study of the cerebral perfusion response to sodium nitrite infusion during the early brain injury period in 15 low grade (World Federation of Neurosurgeons grade 1–2) SAH patients. Patients were randomly assigned to receive sodium nitrite at 10 mcg/kg/min or saline placebo. Assessment occurred following endovascular aneurysm occlusion, mean time after ictus 66h (range 34–90h). Cerebral perfusion was quantified before infusion commencement and after 3 hours, using multi-post labelling delay (multi-PLD) vessel encoded pseudocontinuous arterial spin labelling (VEPCASL) magnetic resonance imaging (MRI). Administration of sodium nitrite was associated with a significant increase in average grey matter cerebral perfusion. Group level voxelwise analysis identified that increased perfusion occurred within regions of the brain known to exhibit enhanced vulnerability to injury. These findings highlight the role of impaired NO bioavailability in the pathophysiology of early brain injury. •Early brain injury occurs in the first 72 h following subarachnoid haemorrhage.•Reduced NO availability and associated cerebral perfusion disruption may play a role.•Using arterial spin labelling MRI we examined the role of NO pathway on perfusion.•In vivo manipulation NO levels with sodium nitrite increased cerebral perfusion.