Na+/Ca2+-exchanger-mediated Mn2+-enhanced 1H2O MRI in hypoxic, perfused rat myocardium

Daniel C. Medina, Dawn M. Kirkland, Masoud F. Tavazoie, Charles S. Springer, Steven E. Anderson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalContrast Media and Molecular Imaging
Volume2
Issue number5
DOIs
StatePublished - Sep 2007

Keywords

  • Ca
  • Heart
  • Hypoxia
  • KB-R7943
  • MEMRI
  • MRI
  • Mn
  • Na

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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