BackgroundQuantification of myocardial “area at risk” (AAR) and myocardial infarction (MI) zone is critical for assessing novel therapies targeting myocardial ischemia–reperfusion (IR) injury. Current “gold‐standard” methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride (TTC), requiring manual slicing and analysis. We aimed to develop and validate a high‐resolution 3‐dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR.Methods and ResultsForty‐eight hours after IR was induced, rats were anesthetized and gadopentetate dimeglumine was administered intravenously. After 10 minutes, the coronary artery was re‐ligated and a solution containing iron oxide microparticles and Evan's Blue was infused (for comparison). Hearts were harvested and transversally sectioned for TTC staining. Ex vivo MR images of slices were acquired on a 9.4‐T magnet. T2* data allowed visualization of AAR, with microparticle‐associated signal loss in perfused regions. T1 data demonstrated gadolinium retention in infarcted zones. Close correlation (r=0.92 to 0.94; P<0.05) of MRI and Evan's Blue/TTC measures for both AAR and MI was observed when the combined techniques were applied to the same heart slice. However, 3D MRI acquisition and analysis of whole heart reduced intra‐observer variability compared to assessment of isolated slices, and allowed automated segmentation and analysis, thus reducing interobserver variation. Anatomical resolution of 81 μm3 was achieved (versus ≈2 mm with manual slicing).ConclusionsThis novel, yet simple, MRI technique allows precise assessment of infarct and AAR zones. It removes the need for tissue slicing and provides opportunity for 3D digital analysis at high anatomical resolution in a streamlined manner accessible for all laboratories already performing IR experiments.

Objectives: To assess the long term efficacy of and risks associated with computer aided oral anticoagulation for non-rheumatic atrial fibrillation (NRAF) in a district hospital setting. Design: Retrospective, age stratified, event driven clinical database analysis. Setting: District general hospital. Participants: 739 patients receiving warfarin for NRAF between 1996 and 2001. Patients were selected from an anticoagulation database through appropriate filter settings. Main outcome measures: Anticoagulation control (international normalised ratio (INR)) and hospitalisations for bleeding complications, thromboembolic events, and stroke. Results: Over 1484 patient-years, computer assisted anticoagulation was uncontrolled in 38.3% of patients (INR , 2.0 or . 3.0). No significant differences in INR control were observed with respect to patient age (, 65, 65-75, and . 75 years), although to achieve adequate control of anticoagulation, the frequency of testing increased significantly with age. Annual risks of bleeding complications, thromboembolism, and stroke were 0.76%, 0.35%, and 0.84%, respectively. No significant differences in these events were observed between the three age groups studied. Patients who had thromboembolic events and haemorrhagic complications were significantly more likely to have been under-anticoagulated (INR , 2.0) and over-anticoagulated (INR . 3.0), respectively, at the time of their clinical event.Conclusions: Computerised long term oral anticoagulation for NRAF in a community setting of elderly and diverse patients is safe and effective. Anticoagulation control, bleeding events, thromboembolic episodes, and stroke rates are directly comparable with those reported in major clinical trials. The authors therefore support the strategy of rate control with long term oral anticoagulation for NRAF in general clinical practice.

Despite improvements in revascularization after a myocardial infarction, coronary disease remains a major contributor to global mortality. Neutrophil infiltration and activation contributes to tissue damage, via the release of myeloperoxidase (MPO) and formation of the damaging oxidant hypochlorous acid. We hypothesized that elevation of thiocyanate ions (SCN−), a competitive MPO substrate, would modulate tissue damage. Oral dosing of rats with SCN−, before acute ischemia–reperfusion injury (30 min occlusion, 24 h or 4 week recovery), significantly reduced the infarct size as a percentage of the total reperfused area (54% versus 74%), and increased the salvageable area (46% versus 26%) as determined by MRI imaging. No difference was observed in fractional shortening, but supplementation resulted in both left-ventricle end diastolic and left-ventricle end systolic areas returning to control levels, as determined by echocardiography. Supplementation also decreased antibody recognition of HOCl-damaged myocardial proteins. SCN− supplementation did not modulate serum markers of damage/inflammation (ANP, BNP, galectin-3, CRP), but returned metabolomic abnormalities (reductions in histidine, creatine and leucine by 0.83-, 0.84- and 0.89-fold, respectively), determined by NMR, to control levels. These data indicate that elevated levels of the MPO substrate SCN−, which can be readily modulated by dietary means, can protect against acute ischemia–reperfusion injury.