Abstract 8093: Inorganic Nitrite Induces Second-Window Preconditioning in Healthy Volunteers

Background Inorganic nitrite has been shown to induce preconditioning in a variety of animal and tissue models. Work from our group has shown that nitrite can induce periconditioning in a human model of ischemia-reperfusion injury, which is influenced by ALDH2 genotype. We investigated whether systemic inorganic nitrite infusion, given 24 hours before the onset of ischemia, protects human forearm endothelium from ischemia-reperfusion injury in unselected healthy volunteers. Methods 12 healthy volunteers were randomised to 2 groups. Inorganic nitrite or saline placebo was given intravenously at a dose of 1 mcg/kg/min for 10 minutes, 24 hours before the onset of studies. Venous occlusion plethysmography, using escalating doses of intra-arterial acetylcholine, was used to measure forearm endothelial function before and 15 minutes after 20 minutes of total forearm ischemia. Results Ischemia-reperfusion injury caused significant endothelial dysfunction in those that had received a placebo infusion (n=5, p<0.05). Conversely, the group that received systemic nitrite 24 hours before study were protected from IR injury (p=0.78 for a difference pre- and post-ischemia). Discussion This study shows, for the first time in man, that a simple cost-effective intervention has potential to prevent injury in situations where significant ischemia-reperfusion injury is predictable, such as in cardiac surgery. More speculatively, this mechanism may be involved in the health benefits of a diet containing nitrite-rich green leafy vegetables. This result invites further study in the form of clinical trials.