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.
Medina
Daniel C
DC
College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA.
Kirkland
Dawn M
DM
Tavazoie
Masoud F
MF
Springer
Charles S
CS
Anderson
Steven E
SE
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