Introduction: 

Inhaled nitric oxide (NOi) exerts extra-pulmonary effects by formation of circulating nitrite and/or S-nitrosohemoglobin. Both carriers release NO when hemoglobin desaturates, and may thus redistribute blood flow selectively to areas in need. The latter concept is the inverse of the classical "steal effect" of conventional vasodilators in ischemic diseases, and has been termed "Robin Hood effect". Here, we tested the hypothesis that NOi may improve left ventricular function and reduce infarct size by the Robin Hood effect in a rat model of myocardial infarction (MI).

Methods: 

In anesthetized male Sprague-Dawley rats, MI was induced by occlusion of the left anterior descending (LAD) artery. After 2 h of LAD occlusion, animals were either sacrificed (n=10 each) or reperfusion was re-instated for 3 h (n=7 each). In each protocol, NOi was administered at 50 ppm during the ischemic interval only. Control rats were ventilated with room air alone. Arterial pressure (AP), left ventricular pressure (LVP) and contractility (dp/dt) were continuously monitored, while infarct size and area at risk (AAR) were determined post mortem by methylene-blue and tetrazolium red staining.

Results: 

2 h after LAD occlusion, mean AP (87.22.4 mmHg in NOi versus 62.65.4 mmHg in controls), systolic LVP (102.22.6 vs. 90.12.8 mmHg) and dp/dt (max) (245194 versus 1876137 mmHg/s) were significantly (*p<0.05) higher in rats receiving NOi as compared to untreated controls. In ischemia without reperfusion, NOi also reduced AAR from 39.71.8 to 28.70.9% of the left ventricle. After additional 3 h of reperfusion, mean AP (75.13.1 vs. 57.63.9 mmHg), systolic LVP (92.53.2 vs. 83.42.1 mmHg) and dp/dt (max) (2214101 versus 153694 mmHg/s) were still higher in rats which had received NOi during the ischemic interval as compared to controls, while infarct size was reduced from 24.72.5% to 17.40.3%.

Conclusion: 

Inhalation of nitric oxide improves left ventricular function and reduces infarct size during ischemia presumably by induction of a Robin Hood effect, i.e. by selectively redistributing blood flow to areas at risk. Inhaled nitric oxide may therefore present a novel and promising clinical strategy to improve collateral blood flow in myocardial ischemia until reperfusion has been re-established.