Functional electron paramagnetic resonance imaging of ischemic rat heart: Monitoring of tissue oxygenation and pH

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Purpose—EPR imaging in spectral-spatial domain with application of soluble paramagnetic probes provides an opportunity for spatially-resolved functional measurements on living objects. The main purpose of this work was development of EPR methods for visualization of oxygenation and acidosis of ischemic myocardium. Methods—EPR oxygen measurements were performed using isotopically substituted 2H,15Ndicarboxyproxyl. The radical has EPR linewidth of 320 mG and oxygen-induced line broadening of 0.53 mG/mmHg providing oxygen sensitivity down to 5 μM. pH measurements were performed using previously developed pH-sensitive imidazoline nitroxide. The radical has EPR spectrum with pH-dependable hyperfine splitting, pK = 6.6, providing pH sensitivity of about 0.05 units in physiological range. Results—EPR imaging of isolated and perfused rat hearts were performed in 2D + spectral domain. Spatial resolution of the measurements was about 1.4 mm. Marked tissue hypoxia was observed in ischemic area of the hearts after occlusion of left anterior descending coronary artery. Tissue oxygenation was partly restored upon reperfusion. EPR mapping of myocardial pH indicated acidosis of ischemic area down to pH 6.7 – 6.8. Conclusion—This work demonstrates capability of low-field EPR and the nitroxide spin probes for mapping of myocardial oxygenation and pH. The developed approaches might be used for noninvasive investigation of microenvironment on living objects.