Background-The aim of this study was to determine whether edema imaging by T2-weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate the area at risk in reperfused myocardial infarction. We hypothesized that the size of the area at risk during a transient occlusion would be similar to the T2-weighted hyperintense region observed 2 days later, that the T2-weighted hyperintense myocardium would show partial functional recovery after 2 months, and that the T2 abnormality would resolve over 2 months. Methods and Results-Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by reperfusion. The area at risk, as measured with microspheres (9 animals), was comparable to the size of the hyperintense zone on T2-weighted images 2 days later (43.4Ϯ3.3% versus 43.0Ϯ3.4% of the left ventricle; PϭNS), and the 2 measures correlated (Rϭ0.84). The infarcted zone was significantly smaller (23.1Ϯ3.7; both PϽ0.001). To test whether the hyperintense myocardium would exhibit partial functional recovery over time, 8 animals were imaged on day 2 and 2 months later. Systolic strain was mapped with displacement encoding with stimulated echoes. Edema, as detected by a hyperintense zone on T2-weighted images, resolved, and regional radial systolic strain partially improved from 4.9Ϯ0.7 to 13.1Ϯ1.5 (Pϭ0.001) over 2 months. Conclusions-These findings are consistent with the premise that the T2 abnormality depicts the area at risk, a zone of reversibly and irreversibly injured myocardium associated with reperfused subendocardial infarctions. The persistence of postischemic edema allows T2-weighted CMR to delineate the area at risk 2 days after reperfused myocardial infarction.

Background-Accumulating evidence suggests that the ubiquitous anion nitrite (NO 2 Ϫ ) is a physiological signaling molecule, with roles in intravascular endocrine nitric oxide transport, hypoxic vasodilation, signaling, and cytoprotection. Thus, nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infarction. The specific aims of this study were (1) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infarction and (2) to determine the relative role of nitrite versus chemical intermediates, such as S-nitrosothiols. Methods and Results-We evaluated infarct size, microvascular perfusion, and left ventricular function by histopathology, microspheres, and magnetic resonance imaging in 27 canines subjected to 120 minutes of coronary artery occlusion. This was a blinded, prospective study comparing a saline control group (nϭ9) with intravenous nitrite during the last 60 minutes of ischemia (nϭ9) and during the last 5 minutes of ischemia (nϭ9). In saline-treated control animals, 70Ϯ10% of the area at risk was infarcted compared with 23Ϯ5% in animals treated with a 60-minute nitrite infusion. Remarkably, a nitrite infusion in the last 5 minutes of ischemia also limited the extent of infarction (36Ϯ8% of area at risk). Nitrite improved microvascular perfusion, reduced apoptosis, and improved contractile function. S-Nitrosothiol and iron-nitrosyl-protein adducts did not accumulate in the 5-minute nitrite infusion, suggesting that nitrite is the bioactive intravascular nitric oxide species accounting for cardioprotection. Conclusions-Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infarction. (Circulation. 2008;117:2986-2994.)