Abstract 10310: Sodium Nitrite is a Pre-Conditioning but Not a Post-Conditioning Agent in a Human Forearm Model of Ischaemia/Reperfusion Injury
Background: The relatively inert nitric oxide (NO) metabolite nitrite (NO2-) has recently been shown to protect against ischaemia/reperfusion (IR) injury in-vitro. We investigated whether sodium nitrite (NaNO2) is a pre-conditioning (Pre-C) or a post-conditioning (Post-C) agent in a well validated human model of acute vascular injury.
Method: 19 healthy subjects underwent endothelial function testing (i.e. high-resolution ultrasound assessment of brachial artery flow mediated dilatation (FMD)) before and 20 minutes after a 20 minute period of ipsilateral whole arm ischaemia (created by upper-arm cuff inflation to 200mmHg). On separate days each subject received an intravenous infusion of either NaNO2 (1.5umol/min for 20min) or 0.9% saline (same regime) into the contralateral arm. The study-infusion was given either before (i.e. Pre-C study, n=10) or during forearm ischaemia (i.e. Post-C study, n=9).
Results: In the two saline studies mean FMD fell from 6.8% to 3.9% (Pre-C) and 8.6% to 5.6% (Post-C) as a result of the IR insult (i.e. absolute reduction in FMD (mean±SEM): −2.9±0.9% & −3.0±0.9%). NaNO2 treatment as a pre-conditioning agent greatly attenuated the degree of endothelial dysfunction induced by IR (−0.7±0.5%, p<0.01, repeated measures ANOVA with Bonferroni post-test; see figure.) However, in the NaNO2/Post-C study the degree of ischaemia-induced endothelial dysfunction remained unchanged from that measured in both saline studies (3.2±0.7%, p>0.05, same test).
Conclusions: NaNO2 protects against acute IR-induced endothelial injury when administered before by not after ischaemic provocation. Thus NaNO2 has greater potential to protect against IR injury in planned procedures (e.g. coronary artery bypass surgery) rather than in spontaneous ischaemic events (e.g. myocardial infarction).
- © 2010 by American Heart Association, Inc.