Inhaled Nitric Oxide Augments Cerebral Blood Flow in Healthy Subjects

Introduction: Optimizing cerebral blood flow (CBF) is a cornerstone of clinical management for a number of neurologic disease states, most notably acute ischemic stroke. Transdermal nitric oxide donors are being investigated for acute stroke, though the effect of inhaled nitric oxide (iNO) on CBF remains largely unknown. Here we aim to quantify the cerebral hemodynamic response to iNO in healthy volunteers. Methods: Cerebral perfusion was measured during three doses of iNO (5ppm, 10ppm, and 20ppm) using the iNOMAX system (Mallinckrodt Pharmaceuticals) in 20 healthy volunteers. Continuous measurements of microvascular CBF were made with diffuse correlation spectroscopy (DCS), while middle cerebral artery mean flow velocity (MFV) was measured with transcranial Doppler. Cardiopulmonary status and nitric oxide toxicity (i.e. NO 2 ) were continuously monitored for safety. Results: Overall, iNO was safe and well tolerated. All subjects completed the protocol in its entirety. All 3 doses of iNO resulted in a small but statistically significant increase in microvascular CBF as compared to baseline (figure). No significant changes in MFV were identified (figure). During administration of iNO, there was no detrimental effect on blood pressure, nor was there any significant accumulation of toxic metabolites. Conclusions: iNO was safe and produced a small but significant increase in microvascular CBF in healthy volunteers. Future studies are warranted to determine the optimal dose of iNO and to explore the effect in acute ischemic stroke patients.