Indirectly probing Ca(2+) handling alterations following myocardial infarction in a murine model using T(1)-mapping manganese-enhanced magnetic resonance imaging.
Prolonged ischemia causes cellular necrosis and myocardial infarction (MI) via intracellular calcium (Ca(2+)) overload. Manganese-enhanced MRI indirectly assesses Ca(2+) influx movement in vivo as manganese (Mn(2+)) is a Ca(2+) analog. To characterize myocardial Mn(2+) efflux properties, T(1)-mapping manganese-enhanced MRI studies were performed on adult male C57Bl/6 mice in which Ca(2+) efflux was altered using pharmacological intervention agents or MI-inducing surgery. Results showed that (1) Mn(2+) efflux rate increased exponentially with increasing Mn(2+) doses; (2) SEA0400 (a sodium-calcium exchanger inhibitor) decreased the rate of Mn(2+) efflux; and (3) dobutamine (a positive inotropic agent) increased the Mn(2+) efflux rate. A novel analysis technique also delineated regional features in the MI mice, which showed an increased Mn(2+) efflux rate in the necrosed and peri-infarcted tissue zones. The T(1)-mapping manganese-enhanced MRI technique characterized alterations in myocardial Mn(2+) efflux rates following both pharmacologic intervention and an acute MI. The Mn(2+) efflux results were consistent with those in ex vivo studies showing an increased Ca(2+) concentration under similar conditions. Thus, T(1)-mapping manganese-enhanced MRI has the potential to indirectly identify and quantify intracellular Ca(2+) handling in the peri-infarcted tissue zones, which may reveal salvageable tissue in the post-MI myocardium.
Waghorn
Benjamin
B
Small Animal Imaging, Department of Radiology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Schumacher
Autumn
A
Liu
Jimei
J
Jacobs
Stephanie
S
Baba
Akemichi
A
Matsuda
Toshio
T
Yanasak
Nathan
N
Hu
Tom C-C
TC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002712:Chlorides / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D015336:Molecular Probe Techniques; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C025340:manganese chloride; D002118:Calcium