Na+/Ca2+-exchanger-mediated Mn2+-enhanced (1)H2O MRI in hypoxic, perfused rat myocardium.
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.
College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA.
Daniel C
DC
Medina
Dawn M
DM
Kirkland
Masoud F
MF
Tavazoie
Charles S
CS
Springer
Steven E
SE
Anderson
D000818:Animals; D002318:Cardiovascular Diseases / Q000175:diagnosis; D015687:Cell Hypoxia; D003287:Contrast Media / Q000378:metabolism*; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D003287:Contrast Media; D019831:Sodium-Calcium Exchanger; D008345:Manganese