Na + /Ca 2+ ‐exchanger‐mediated Mn 2+ ‐enhanced 1 H 2 O MRI in hypoxic, perfused rat myocardium

Paramagnetic Mn 2+ has emerged in the search for non‐invasive magnetic resonance imaging (MRI) techniques to monitor Ca 2+ in diagnostic and prognostic cardiovascular disease tests because it both alters MRI contrast and behaves as a Ca 2+ ‘surrogate’ in vivo . However, the reliance on macroscopically averaged measurements to infer microscopic processes constitutes a major limitation of MRI. This investigation circumvents this limitation and contributes an MRI‐based myocardial Ca 2+ ‐transporter assay, which probes the Na + /Ca 2+ ‐exchanger involvement in Mn 2+ (and presumably Ca 2+ ) transport by virtue of its response to pharmacological inhibition. In the model employed herein, ex vivo arrested rat hearts underwent normoxia and then hypoxia while a constant (hyperkalemic) perfusion minimized flow (and uncontrolled Ca 2+ ‐channel) contributions to Mn 2+ ‐enhanced MRI measurements. The results (i) demonstrate that Mn 2+ (and presumably Ca 2+ ) accumulates via Na + /Ca 2+ ‐exchanger‐mediated transport during hyperkalemic hypoxia and further, (ii) implicate hypo‐perfusion (rather than the diminished participation of an isolated sarcolemmal Ca 2+ ‐transporter) as the mechanism that underlies the reported reductions of Mn 2+ accumulation (relative to healthy myocardium) subsequent to myocardial insults in MRI studies. Although myriad studies have employed Mn 2+ ‐enhanced MRI in myocardial investigations, this appears to be the first attempt to assay the Na + /Ca 2+ ‐exchanger with MRI under highly circumscribed conditions. MRI‐based Ca 2+ ‐transporter assays, such as the Na + /Ca 2+ ‐exchanger assay utilized here, will inevitably impact disciplines in the medical sciences and beyond. Copyright © 2007 John Wiley & Sons, Ltd.