Abstract
Paramagnetic Mn2+ has emerged in the search for non-invasive magnetic resonance imaging (MRI) techniques to monitor Ca2+ in diagnostic and prognostic cardiovascular disease tests because it both alters MRI contrast and behaves as a Ca2+ '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 Ca2+-transporter assay, which probes the Na+/Ca2+-exchanger involvement in Mn2+ (and presumably Ca2+) 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 Ca2+-channel) contributions to Mn2+ enhanced MRI measurements. The results (i) demonstrate that Mn2+ (and presumably Ca2+) accumulates via Na+/Ca2+ -exchanger-mediated transport during hyperkalemic hypoxia and further, (ii) implicate hypo-perfusion (rather than the diminished participation of an isolated sarcolemmal Ca2+-transporter) as the mechanism that underlies the reported reductions of Mn2+ accumulation (relative to healthy myocardium) subsequent to myocardial insults in MRI studies. Although myriad studies have employed Mn2+-enhanced MRI in myocardial investigations, this appears to be the first attempt to assay the Na+/Ca2+-exchanger with MRI under highly circumscribed conditions. MRI-based Ca2+-transporter assays, such as the Na+/Ca2+-exchanger assay utilized here, will inevitably impact disciplines in the medical sciences and beyond.
Original language | English (US) |
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Pages (from-to) | 248-257 |
Number of pages | 10 |
Journal | Contrast Media and Molecular Imaging |
Volume | 2 |
Issue number | 5 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- Ca
- Heart
- Hypoxia
- KB-R7943
- MEMRI
- MRI
- Mn
- Na
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging