Introduction Sodium nitrite (NaNO2) became a popular means of treating angina in the 19th century, as its stable chemical structure allowed for cheap preparation and easy storage. However, the effects were slow and unpredictable and so it fell out of favour as more potent and faster-acting agents became available, (eg, organic nitrates). Recent in vitro evidence shows that nitrite (NO2-) exhibits an enhanced vasodilator effect in hypoxia; an environmental modification which encourages its reduction to nitric oxide (NO). Therefore NaNO2 could potentially be an anti-ischaemic agent at much lower doses than those used historically, and be without the adverse side effects associated with organic nitrates (eg, systemic hypotension and tachyphylaxis).
Method A double-blind, placebo-controlled, cross-over study was performed in 10 subjects with proven myocardial ischaemia documented by exercise tolerance testing and coronary angiography. Two dobutamine stress echocardiography (DSE) studies were performed on each subject: one with 0.9% saline and one with NaNO2, 1.5 μmol/min for 20 min. This dose of NaNO2 has previously been shown to be inert in normoxia but to vasodilate hypoxic tissue. Myocardial ischaemia was identified by the peak systolic velocity (PSV) response during DSE in a six basal-wall segment model of the left ventricle. Using placebo study data-set, walls were classified into tertiles: the lowest tertile of responders of PSV to an increase in heart rate (ΔHR) labelled ischaemia (n=18) and the upper tertile control (n=18). Data was divided into four groups according to the study-infusion received and the myocardial-wall examined: saline/ischaemia, NO2-/ischaemia, saline/control and NO2-/control.
Results Data from each stage of each DSE was plotted on a scatter plot graph with change in (ΔHR) on the x-axis and corresponding change in PSV (ΔPSV) on the y-axis (increase in both values compared to baseline), see Abstract 51 figures 1 and 2. Linear regression analysis of the saline/ischaemia group was lower than the NO2-/ischaemia group, with no overlap in their 95% CI, see Abstract 51 figure 1. In addition, the linear regression gradient of the NO2-/ischaemia group was similar to the saline/control and the NO2-/control gradient, see Abstract 51 figure 2. The peak-dose dobutamine values of ΔPSV/ΔHR were different in the saline/ischaemia group compared to the three other groups (ie, saline/ischaemia =3.7±0.6 cm/s/s, NO2-/ischaemia =8.2±1.0 cm/s/s, saline/control =10.5±1.1 cm/s/s, NO2-/control =8.4±0.7 cm/s/s; p<0.01, repeated-measures ANOVA with Bonferroni post-test). No difference was present between the three other groups.
Conclusions Low-dose NaNO2 delivers a therapeutic effect to ischaemic myocardial tissue in the absence of a vasodilator effect on normoxic tissue. This is the first study in patients to demonstrate a targeted vasodilator effect of NO2- to tissues in need only.
- Sodium nitrite
- stress echocardiography
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